Rhodium(II)-catalyzed equilibration of push-pull carbonyl and ammonium ylides. A computationally based understanding of the reaction pathway

Article abstract of DOI:10.1021/ja001088j

Δ-Diazo esters containing an amido group in the γ-position have been found to undergo a rhodium(II)-catalyzed transformation, producing five-membered ammonium or carbonyl ylides depending on the reaction conditions used. In the absence of an external dipo

Full text of DOI:10.1021/ja001088j

J. Am. Chem. Soc. 2000, 122, 8155-8167
8155
Rhodium(II)-Catalyzed Equilibration of Push-Pull Carbonyl and
Ammonium Ylides. A Computationally Based Understanding of the
Reaction Pathway
Albert Padwa,*,† James P. Snyder,*,† Erin A. Curtis,† Scott M. Sheehan,†
Kimberly J. Worsencroft,† and C. Oliver Kappe*,‡
Contribution from the Department of Chemistry, Emory UniVersity, Atlanta, Georgia 30322, and
Institute of Chemistry, Karl-Franzens-UniVersity Graz, A-8010, Graz, Austria
ReceiVed March 28, 2000
Abstract: R-Diazo esters containing an amido group in the γ-position have been found to undergo a rhodium(II)-
catalyzed transformation, producing five-membered ammonium or carbonyl ylides depending on the reaction
conditions used. In the absence of an external dipolarophile, ammonium ylides are the exclusive products
formed. In most cases these ylides cannot be isolated as they readily undergo sigmatropic rearrangement or
fragmentation reactions. In the presence of typical dipolarophiles such as DMAD or N-phenylmaleimide,
cycloaddition products derived from cyclic carbonyl ylide dipoles are formed as the major products. The rhodium
carbenoid intermediate generated in these reactions can either attack the lone pair of electrons on the amide
nitrogen (ammonium ylide formation) or the lone pair of electrons on the carbonyl oxygen (carbonyl ylide
formation). The experimental observations reflect a catalyst-promoted system of equilibria with a clear-cut
thermodynamic bias. To examine the underlying mechanism in detail, density functional theory (DFT)
calculations were performed on all plausible intermediates, including the full dirhodium tetracarboxylate
functionality. A semiquantitative energy manifold is developed that rationalizes the empirical observations
and provides a detailed picture of the role of the dirhodium(II) catalyst.
Introduction
isomu¨nchnone 2 was easily prepared by treating diazoimide 1
with Rh2(OAc)4 in CH2Cl2 at 80 °C.16 The mesoionic oxazolium
The vast importance of nitrogen heterocycles has stimulated
the development of new methodology for their construction.1-8
Among the most useful methods recently developed are iminium
ion initiated,9-11 free radical induced,12 and tandem Heck
cyclizations.13 Recent publications from our laboratories have
introduced a new general strategy for ring-fused polyhetero-
cycles in which metallo carbenoids derived from diazo carbonyl
precursors play a central role.14 A wide variety of aza-polycycles
can be accessed with high efficiency from the rhodium(II)-
catalyzed reaction of R-diazo keto amides.15 For example,
ylide 2 is the cyclic equivalent of a carbonyl ylide dipole and
(11) Zablocki, J. J. Am. Chem. Soc. 1992, 114, 368. Tietze, L. F.;
Wu¨nsch, J. R.; Noltemeyer, M. Tetrahedron 1992, 48, 2081. Wasserman,
H. H.; Vu, C. B.; Cook, J. D. Tetrahedron 1992, 48, 2101. Luedtke, G.;
Westling, M.; Livinghouse, T. Tetrahedron 1992, 48, 2209. Overman, L.
E.; Robichauid, A. J. J. Am. Chem. Soc. 1989, 111, 300. Heitz, M. P.;
Overman, L. E. J. Org. Chem. 1989, 54, 2591. Ruggeri, R. B.; McClure,
K. F.; Heathcock, C. H. J. Am. Chem. Soc. 1989, 111, 1530. Grieco, P. A.;
Parker, D. T. J. Org. Chem. 1988, 53, 3658.
(12) Della, W. E.; Knill, A. M. J. Org. Chem. 1996, 61, 7529. Zard, S.
Z. Synlett 1996, 1148. Bachi, M. D.; Denenmark, D. J. Org. Chem. 1990,
55, 3442. Bachi, M. D.; Balanov, A.; Bar-Ner, N. J. Org. Chem. 1994, 59,
7752.
(13) Heck, R. F. Organic Reactions; Wiley and Sons: New York, 1982;
Vol. 27, Chapter 2. Grigg, R.; Loganathan, V.; Sridharan, V.; Stevenson,
P.; Sukirthalingam, S.; Worakun, T. Tetrahedron 1996, 52, 11479. Grigg,
R.; Sridharan, V.; Xu, L. H. J. Chem. Soc., Chem. Commun. 1995, 18,
1903.
† Emory University.
‡ Karl-Franzens-University.
(1) Fang, F. G.; Prato, M.; Kim, G.; Danishefsky, S. J. Tetrahedron Lett.
1989, 30, 3625. Fang, F. G.; Danishefsky, S. J. Tetrahedron Lett. 1989,
30, 2747. Fang, F. G.; Maier, M. E.; Danishefsky, S. J. J. Org. Chem. 1990,
55, 831. Kim, G.; Chu-Moyer, M. Y.; Danishefsky, S. F. J. Am. Chem.
Soc. 1990, 112, 2003.
(2) Kametani, T.; Yukawa, H.; Honda, T. J. Chem. Soc., Chem. Commun.
1986, 651.
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60, 2704. Padwa, A.; Price, A. T. J. Org. Chem. 1995, 60, 6258.
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F. G.; Naidu, B. N. J. Am. Chem. Soc. 1994, 116, 8420.
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M.; Ibata, T. Chem. Lett. 1975, 499. Osterhout, M. H.; Nadler, W. R.; Padwa,
A. Synthesis 1994, 123. Padwa, A.; Marino, J. P., Jr.; Osterhout, M. H. J.
Org. Chem. 1995, 60, 2704. Padwa, A.; Hertzog, D. L.; Nadler, W. R. J.
Org. Chem. 1994, 59, 7072. Marino, J. P., Jr.; Osterhout, M. H.; Price, A.
T.; Semones, M. A.; Padwa, A. J. Org. Chem. 1994, 59, 5518. Padwa, A.;
Hertzog, D. L.; Nadler, W. R.; Osterhout, M. H.; Price, A. T. J. Org. Chem.
1994, 59, 1418. Hertzog, D. L.; Austin, D. J.; Nadler, W. R.; Padwa, A.
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10.1021/ja001088j CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/10/2000

8156 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Padwa et al.
readily undergoes intramolecular 1,3-dipolar cycloaddition to
give novel cycloadducts of type 3. This reaction is an integral
part of our program aimed at developing new cascade reactions
and achieving the total synthesis of various alkaloids.17
Our more recent achievements in this area involve the use
of diazo ketoamides such as 4.18 Attack of the amido oxygen
at the rhodium carbenoid produces a push-pull carbonyl ylide
dipole (i.e., 5) that is isomeric with the isomu¨nchnone class of
mesoionic betaines. Intramolecular cycloaddition occurs to
depend on the conformational flexibility of the carbenoid and
the reaction conditions employed.22
Parallel to the application of dirhodium(II) tetracarboxylates
to synthetic targets, we have initiated a computational examina-
tion of the structure and mechanism of intermediates along
pathways facilitated by the bimetallic catalyst. While many
previous theoretical studies have examined aspects of the
electronic structure of Rh2(O2CR)4 agents and their cations,23,24
very few have investigated key reaction intermediates. Notable
exceptions are the extended Huckel evaluation of a parent
rhodium carbenoid, methylene(dirhodium tetraacetamide), which
predicted a very low Rh-C barrier to rotation for the carbenoid
ligand,25a a ZINDO estimate of charges and frontier orbital
energies for RhL4RhdCH2,25b and an MM2/ZINDO study of
rhodium-mediated intramolecular C-H insertion.26 More re-
cently, we reported a density functional theory (DFT) examina-
tion of the solvated dirhodium cage structure and the corre-
sponding methylene carbenoids. A novel proposal for Rh-C
bonding emerged along with a proposition for the role played
by the distal rhodium atom in the Rh-Rh-C train in the metal
carbenoids.27
In the present contribution, we offer an intimate description
of the action of the dirhodium catalyst on diazo ketone substrates
followed by regeneration of the promoter concomitant with
product formation. During the course of the overall transforma-
tion, a set of rhodium-containing organic complexes leads
stepwise to the formation and release of carbonyl and am-
monium ylides responsible for the ultimate catalyst-free steps
in synthesis (Scheme 1). Each of the proposed structures has
been treated to full DFT optimization to confirm existence as
an energy minimum and to permit assessment of changes in
bonding and relative energy. In sum, the mechanistic portrait
links the experimental observations to unobserved intermediates
and places the entire pathway on a semiquantitative footing.
furnish heterocycles such as 6 in good yield, provided that the
tether engaged in ring formation carries a carbonyl group (i.e.,
X ) O). In a recent report,19 we demonstrated that these transient
push-pull carbonyl ylides can be used as an entry to 2,3,3-
trisubstituted indole alkaloids. The successful preparation of
dihydrovindorosine 9 from diazo amide 7 (via cycloadduct 8)
establishes the merit of the method for constructing the
pentacyclic skeleton of the aspidosperma alkaloid ring system.20
This sequence is particularly attractive for further study as four
of the stereocenters were formed in one step with a high degree
of stereocontrol.
Results and Discussion
Rhodium(II)-Catalyzed Decomposition of Cyclopropyl
Diazo Ketoamides. Our earlier studies dealing with the Rh(II)-
catalyzed reaction of cyclopropyl-substituted diazo carbonyls
involved interaction of the metallo carbene with alkyl and aryl
ketones.28 We felt that it would prove enlightening to extend
these earlier studies to include the related amido functionality
(22) Kappe, C. O. Tetrahedron Lett. 1997, 38, 3323.
(23) For reviews of the early work, see: Jardine, F. H.; Sheridan, P. S.
ComprehensiVe Coordination Chemistry, IV; Wilkinson, G., Ed.; Pergamon
Press: New York, 1987; pp 944-947. Cotton, F. A.; Walton, R. A. Multiple
Bonds Between Metal Atoms; R. E. Krieger Publishing Co.: Malabar, FL,
1988; p 369.
(24) Mougenot, P.; Demuynck, J.; Benard Chem. Phys. Lett. 1987, 136,
279. Rizzi, G. A.; Casarin, M.; Tondello, E.; Piraino, P.; Granozzi, G. Inorg.
Chem. 1987, 26, 3406. Cotton, F. A. Feng, Inorg. Chem. 1989, 28, 1180.
Bear, J. L.; Yao, C.-L.; Liu, L.-M.; Capdevielle, F. J.; Korp, J. D.; Albright,
T. A.; Kang, S.-K.; Kadish, K. M. Inorg. Chem. 1989, 28, 1254. X. Cotton,
F. A.; Dikarev, E. V.; Feng. X. Inorg. Chim. Acta 1995, 237, 19. Cotton,
F. A.; Feng, X. J. Am. Chem. Soc. 1997, 119, 7514. Cotton, F. A.; Feng,
X. J. Am. Chem. Soc. 1998, 120, 3387. Kawamura, T.; Maeda, M.;
Miyamoto, M.; Usami, H.; Imaeda, K.; Ebihara, M. J. Am. Chem. Soc.
1998, 120, 8136. Lichtenberger, D. L.; Pollard, J. R.; Lynn, M. A.; Cotton,
F. A.; Feng, X. J. Am. Chem. Soc. 2000, 122, 3182.
To further implement and develop this strategy, we have
undertaken a study of the effect of different amido groups on
the efficiency of dipole formation. The model system we
selected allowed for good versatility in assembling the different
amido substitution patterns and involved using cyclopropanated
diazo ketoamides of type 10. The results obtained show that
the Rh(II)-catalyzed behavior of these compounds can lead to
both push-pull carbonyl ylides and/or ammonium ylides.21
A
related process was encountered with the diazoacetylurea
system. In this case, the product distribution was found to
(16) Padwa, A.; Brodney, M. A.; Marino, J. P., Jr.; Osterhout, M. H.;
Price, A. T. J. Org. Chem. 1997, 62, 67.
(17) Padwa, A.; Brodney, M. A.; Marino, J. P., Jr.; Sheehan, S. M. J.
Org. Chem. 1997, 62, 78. Sheehan, S. M.; Padwa, A. J. Org. Chem. 1997,
62, 438.
(18) Weingarten, M. D.; Prein, M.; Price, A. T.; Snyder, J. P.; Padwa,
A. J. Org. Chem. 1997, 62, 2001.
(19) Padwa, A.; Price, A. T. J. Org. Chem. 1995, 60, 6258.
(20) Saxton, J. E. Nat. Prod. Rep. 1993, 10, 349.
(21) Curtis, E. A.; Worsencroft, K. J.; Padwa, A. Tetrahedron Lett. 1997,
38, 3319.
(25) (a) Doyle, M. P.; Winchester, W. R.; Hoorn, J. A. A.; Lynch, V.;
Simonsen, S. H.; Ghosh, R. J. Am. Chem. Soc. 1993, 115, 9968. (b) Padwa,
A.; Austin, D. J.; Price, A. T.; Semones, M. A.; Doyle, M. P.; Protopopova,
M. N.; Winchester, W. R.; Tran, A. J. Am. Chem. Soc. 1993, 115, 8669.
(26) Taber, D. F.; You, K. K.; Rheingold, A. L. J. Am. Chem. Soc. 1996,
118, 547. Taber, D. F.; Malcolm, S. C. J. Org. Chem. 1998, 63, 3717.
(27) Sheehan, S. M.; Padwa, A.; Snyder, J. P. Tetrahedron Lett. 1998,
39, 949.
(28) Curtis, E. A.; Sandanayaka, V. P.; Padwa, A. Tetrahedron Lett. 1995,
36, 1989. Padwa, A.; Curtis, E. A.; Sandanayaka, V. P. J. Org. Chem. 1996,
61, 73.

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Rh(II)-Catalyzed Equilibration of CO and NH4 Ylides
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8157
in order to more clearly define the role of the interacting
carbonyl group for dipole formation. In this spirit, we prepared
several amido-substituted diazo esters and examined their Rh(II)-
catalyzed behavior. Treatment of R-diazo ketoamide 10 with
Rh2(OAc)4 at 80 °C in benzene with dimethyl acetylenedicar-
boxylate afforded the expected dipolar cycloadduct 11 in 87%
yield. The cycloaddition also proceeded readily with N-
carried out. In this case, the reaction of 20 in the presence of
DMAD afforded cycloadduct 21 (57%) together with the
rearranged lactam 22 (42%). When N-phenylmaleimide was
used as the trapping agent, a mixture of 22 (40%) and the ring-
opened product 23 (60%), derived from the expected dipolar
cycloadduct, was obtained. In the absence of an external
dipolarophile, lactam 22 was isolated in 70% yield. Once again,
the formation of 22 can be attributed to the initial generation
of an ammonium ylide followed by a 1,2-benzyl shift. Related
1,2-shifts of cyclic ammonium ylides derived from the reaction
of tertiary amines with R-diazo carbonyl compounds have been
described by West and co-workers,33 thereby providing good
analogy for the suggested mechanism. It would appear as though
the highly electrophilic carbenoid center can either attack the
lone pair of electrons on the amide nitrogen (ammonium ylide
formation) or the lone pair of electrons on the carbonyl oxygen
(carbonyl ylide formation).
Products derived from both a carbonyl ylide and an am-
monium ylide were also encountered with diazo ketoamide 24.
When the Rh(II)-catalyzed reaction of 24 was carried out in
the presence of DMAD, a mixture of lactam 25 (8%) and
cycloadduct 26 (92%) was obtained. With N-phenylmaleimide,
phenylmaleimide, giving rise to cycloadduct 12 in 42% isolated
yield as a single diastereomer. We assume that 12 corresponds
to the exo isomer, as previously established in the cycloaddition
chemistry of related diazo ketones.28,29 The transition state
leading to the endo isomer suffers from unfavorable steric
factors, and consequently, the exo orientation is favored. An
analogous set of products [i.e. 14 (87%) and 15 (80%)] was
obtained with the carbomethoxy-substituted amido diazoester
13. While attempting to purify cycloadduct 15 on a silica gel
column, we noted that it was partially converted to dihydroben-
zofuran 17. Assuming that the conversion of 15 to 17 was the
consequence of an acid-catalyzed reaction, we treated a sample
of 15 with BF3‚OEt2 and isolated 17 in 85% yield. The
formation of 17 proceeds by an initial oxy-bridge ring opening
followed by a subsequent dehydration to give 16 as a nonisolable
intermediate which reacts further by an acid-catalyzed cyclo-
propyl ketone rearrangement.30-32 The facility of the process
is undoubtedly related to the aromaticity gained in the final step.
When the reaction of 10 was carried out in the absence of an
external dipolarophile, the rearranged lactam 19 was isolated
in 62% yield. The formation of 19 can be attributed to the
generation of ammonium ylide 18 followed by a 1,2-phenyl
shift.
a similar mixture of 25 (34%) and the ring-opened cycloadduct
27 (66%) was realized. In the absence of any trapping agent,
24 furnished lactam 25 in 93% yield. The formation of this
product can readily be rationalized in terms of R,R-fragmentation
of ethylene from a transient ammonium ylide. Indeed, am-
monium ylides possessing an R-hydrogen are known to undergo
an elimination reaction to provide the corresponding amine and
alkene, thereby providing good precedent for the formation of
25.34-38
Extension of the carbenoid cyclization-cycloaddition se-
quence with the related N-benzyl-N-methyl amide 20 was also
(29) Padwa, A.; Chinn, R. L.; Hornbuckle, S. F.; Zhang, Z. J. J. Org.
Chem. 1991, 56, 3271.
(30) Schweizer, E. E.; Kopay, C. M. J. Org. Chem. 1971, 36, 1489.
(31) Danishefsky, S.; Dynak, J. Tetrahedron Lett. 1975, 79.
(32) Saalfrank, R. W.; Gu¨ndel, J.; Rossmann, G.; Hanek, M.; Rost, W.;
Peters, K.; von Schnering, H. G. Chem. Ber. 1990, 123, 1175.
(33) West, F. G.; Naidu, B. N. J. Org. Chem. 1994, 59, 6051. West, F.
G.; Naidu, B. N.; Tester, R. W. J. Org. Chem. 1994, 59, 6892.

8158 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Padwa et al.
Rhodium(II)-Catalyzed Transformation of Diazo Acetyl
Ureas. To compare the reactivity of the above push-pull
carbonyl ylide dipoles (i.e., 5) with the analogous isomu¨nchnone
systems (i.e., 2), we next investigated the rhodium(II)-catalyzed
decomposition of diazoacetylurea 28. The reaction of 28 in the
presence of rhodium(II) acetate led to both the isomu¨nchnone
dipole 31 and ammonium ylide 29.22,39 In contrast to ammonium
ylides of type 18, ylide 29 could be isolated as a crystalline
solid (68%). The structure of this persistently stable five-
treated with DMAD in refluxing toluene. The mechanism
probably involves Michael addition of the anionic carbon center
in ylide 29 to the triple bond in DMAD. The resulting zwitterion
36 then rearranges to pyridine 30 according to the pathway
shown below (61%). The structure of pyridine 30 was estab-
lished unambiguously by X-ray crystallographic analysis.40 With
N-methylmaleimide, no thermal cycloaddition reaction with
ammonium ylide 29 was observed.
Common Features of Reactivity. The common feature in
the rhodium(II)-catalyzed decompositions of the diazo amides
reported above (i.e., 10 13, 20, 24, and 28) is the simultaneous
formation of both ammonium ylides (38) and/or isomeric
carbonyl ylides (39). Although these ylides cannot be isolated
directly in most cases, the identification of trapped and/or
rearranged products leaves little doubt that these species are
formed as intermediates. It appears that in the decomposition
of diazo amides 37 the presumed rhodium carbenoid intermedi-
ate (vide infra) can either attack the lone pair of electrons on
the amide nitrogen (ammonium ylide formation, 37 f 38), or
the lone pair of electrons on the carbonyl oxygen (carbonyl ylide
formation, 37 f 39). The product distribution in all cases is
membered N-acyl ammonium ylide was confirmed by X-ray
analysis.22,40 When the reaction was carried out in the presence
of DMAD, a mixture of ylide 29 (28%), furan 33 (25%), and
pyridine 30 (18%) was obtained. The formation of furan 33
strongly supports the involvement of a mesoionic betaine
intermediate in this process.15,41 1,3-Dipolar cycloaddition of
DMAD with isomu¨nchnone dipole 31 followed by extrusion
of methyl isocyanate from the primary cycloadduct 32 nicely
accommodates the isolation of furan 33. This reaction sequence
is well established in isomu¨nchnone cycloaddition chemistry.41
Using N-methylmaleimide as the trapping reagent, a similar
mixture of ylide 29 (46%) and pyrrolopyridine 35 (24%) derived
from the expected dipolar isomu¨nchnone cycloadduct was
obtained.
markedly dependent on the reaction partner. Whereas in the
absence of trapping agents ammonium ylides (or products
derived thereof) are formed exclusively, the presence of
dipolarophiles (i.e., DMAD or N-phenylmaleimide) can shift
the product ratio toward carbonyl ylides which then undergo a
1,3-dipolar cycloaddition reaction.
The product distribution (ammonium ylide vs carbonyl ylide
formation) is also a direct consequence of the conformational
flexibility of the diazo amides. The rhodium(II)-catalyzed
decomposition of a diazo imide of type 40, where the urea
moiety is constrained in a six-membered ring system, has been
examined.42 Here, the carbenoid intermediate can only attack
the lone pair of electrons on the carbonyl oxygen, thereby
generating exclusively the carbonyl ylide isomer. The “amino-
iso-mu¨nchnone” of type 41 could be isolated as a stable
crystalline solid and was found to undergo 1,3-dipolar cycload-
dition reactions with various dipolarophiles.42
Pyridine 30, on the other hand, arises from the thermal
addition of DMAD to ylide 29. This reaction pathway was
confirmed by an independent experiment in which 29 was
(34) Tomiako, H.; Suzuki, K. Tetrahedron Lett. 1989, 30, 6353.
(35) Kirmse, W.; Arold, H. Chem. Ber. 1968, 101, 1008.
(36) Franzen, V.; Kuntze, H. Liebigs Ann. Chem. 1959, 627, 15.
(37) Saunders, M.; Murray, R. W. Tetrahedron 1960, 11, 1.
(38) Phillips, D. D.; Champion, W. C. J. Am. Chem. Soc. 1956, 78, 5452.
(39) Johnson, A. W. Ylide Chemistry; Academic Press: New York, 1966.
Zugravescu I.; Petrovanu, M. N-Ylide Chemistry; MacGraw-Hill: New York,
1976. Claus, P. In Houben-Weyl, Vol. E14b; Klaman, D., Hageman, H.,
Eds; Thieme: Stuttgart, 1990; p 210.
(40) The authors have deposited atomic coordinates for structures 29
and 30 with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained on request from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K. Likewise, the
coordinates for any of the DFT-optimized structures in Scheme 1 and Figures
2, 3, 5, and 6 are available upon request.
(41) Osterhout, M. H.; Nadler, W. R.; Padwa, A. Synthesis 1994, 123.
Newton, C. G.; Ramsden, C. A. Tetrahedron 1982, 38, 2965. Ollis, W. D.;
Ramsden, C. A. AdV. Heterocycl. Chem. 1976, 19, 1.
Since the decomposition of diazoacetylurea 28 gives rise to
an isolable and stable ammonium ylide (i.e., 29), we decided
(42) Kappe, C. O.; Peters, K.; Peters, E.-M. J. Org. Chem. 1997, 62,
3109.

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Rh(II)-Catalyzed Equilibration of CO and NH4 Ylides
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8159
Scheme 1. Reversible Dipole Formationin
to investigate this particular system in more detail. We were
particularly intrigued by the possible interconversion of the
isomeric ammonium and carbonyl ylides. Toward this end, the
reaction of ammonium ylide 29 with DMAD was carried out
in the presence of Rh2(OAc)4. Whereas treatment of 29 with
DMAD in the absence of a transition metal catalyst provided
pyridine 30 in good yield (see above), the presence of Rh2-
(OAc)4 led also to the formation of furan 33, along with the
thermal adduct 30. Although furan 33 is only formed in small
amounts (ca. 10%) in this process, these results suggest that in
the presence of a transition metal catalyst (MLn ) Rh2(OAc)4),
the formation of ammonium ylide 29 is reversible, and that 29
rearranges to carbonyl ylide 31 via the carbenoid intermediate
42. Because of the 1,3-dipolar character of ylide 31, this
mesoionic species can undergo cycloaddition with DMAD,
ultimately giving furan 33. In the first step of such a rearrange-
ment process, the transition metal catalyst (MLn) would have
to add to the ammonium ylide (i.e., 29) to form a metal-
stabilized ylide intermediate which then ring opens to give
carbenoid 42. Attack of the electrophilic carbenoid on the lone
pair of electrons on oxygen followed by dissociation then leads
to the free carbonyl ylide (i.e., 31) and the metal catalyst (MLn).
Reversibility of ylide formation from metallo carbenoids has
been suggested to occur in the literature.43,44 The relatively low
yield of 33 can be rationalized by the competitive thermal
process 29 f 30 and the significantly greater thermodynamic
stability of the ammonium ylide vs the carbonyl ylide (vide
infra). Therefore, the transition metal-mediated equilibrium
between ylides 29 and 31 is expected to lie predominantly on
the ammonium ylide side.
Rhodium(II)-Catalyzed Decomposition of R-Diazo Amides
in rhodium carbenoid 45 flanked by reversible equilibria permits
both the interconversion of uncomplexed ylides 48 and 49 and
their subsequent isolation or capture as cycloadducts. Finally,
Scheme 1 allows for the possibility that the penultimate ylides
interconvert through uncomplexed carbene intermediate 50. An
important aspect of the scheme we do not consider is the
inhibition of dirhodium(II) catalyst with Lewis bases. Pirrung
and Morehead have shown that both diazo ketone substrate and
acetonitrile can divert the catalyst.46
A Plausible Mechanistic Scheme. An important element
characterizing the work described above is the invisibility of
the majority of intermediates that most certainly exist along the
reaction pathways. In general, diazoketone and rhodium catalyst
are mixed in the presence of an internal or external dipolarophile
and the final dipolar cycloaddition adducts or the rearranged
ammonium ylide are isolated. Only two examples of well-
characterized intermediates have been observed: nitrogen ylide
29 and carbonyl ylides captured as isomu¨nchnones15 (e.g., 41).
A mechanistic map that considers plausible steps between
starting materials and products is portrayed in Scheme 1.45
Containing structural types proposed above and in numerous
previous literature reports,14 it rationalizes a number of key
observations.
Optimized Structures. Taking the collection of intermediates
in Scheme 1 as a reasonable hypothesis for the chemistry of
both diazo ketoamides and diazo acetylureas, we have performed
density functional theory (DFT) calculations for each of the
structures. Diazo amide 43 with methyl substituents on nitrogen
and a monosubstituted diazo group was selected for the
calculations as a minimal system exemplifying the cyclopropyl
diazo ketoamides. Subsequent complexes 44-47 incorporating
the full rhodium tetracarboxylate cage were treated as the
tetraformate. This level of structural truncation was necessitated
by the desire to optimize geometries of the entire organometallic
complexes including the demanding dirhodium cage. To achieve
this result, we combined a nonlocal DFT method with an
effective core potential at rhodium atoms and the 3-21G basis
set at other atoms for both geometry refinement and initial
energy evaluation. The latter was supplemented by single-point
6-31G* basis set energies and natural population analysis47 (see
Experimental Section for details). As a preliminary, the structure
of ammonium ylide 29 was optimized with the 6-31G* basis
set and compared with its X-ray structure22,40 (Figure 1). For
13 bond lengths, the average absolute difference is 0.013 Å.
For 19 bond angles, the absolute average deviation is 0.84° with
First, the scheme provides a role for the dirhodium tetracar-
boxylate catalyst and its release late in the pathway. Second,
the early irreversible loss of N2 commits the process to products,
be they desired or undesired. That is, the pathway is overall
exergonic. Third, the ambident properties of the amide group
(43) Doyle, M. P. ComprehensiVe Organometallic Chemistry II; Hegedus,
L. Ed.; Pergamon Press: Oxford; Vol. 12, 1995; p 431. Doyle, M. P.;
McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis
with Diazo Compounds; John Wiley and Sons: New York, 1998.
(44) (a) Pirrung, M. C.; Brown, W. L.; Rege, S.; Laughton, P. J. Am.
Chem. Soc. 1991, 113, 8561. (b) Pirrung, M. C.; Morehead, A. J., Jr. J.
Am. Chem. Soc. 1994, 116, 8991.
(46) Pirrung, M. C.; Morehead, A. J., Jr. J. Am. Chem. Soc. 1996, 118,
8162.
(45) The Scheme 1 mechanism for carbenoid generation is essentially a
variation of the original Yates proposal for copper-catalyzed decomposition
of diazoketones; see: Yates, P. J. Am. Chem. Soc. 1952, 74, 5376.
(47) Glendening, E. D.; Reed, A. E.; Carpenter, J. E.; Weinhold, F. NBO
Version 3.1. Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. ReV. 1988,
88, 899.

8160 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Padwa et al.
Table 1. DFT Optimized Structures and NBO Analysis; Selected Bond Distances
basis set energies, aua
bond lengths, Å
bond orders, bob
no.
43
44
45
46
47
48
49
50
3-21G
6-31G*
C-Rh
Rh-Rh
C-Rh
Rh-Rh
-622.626 761
-1594.382 723
-1485.467 143
-1485.541 203
-1485.530 215
-513.740 173
-513.726 078
-513.652 747
-971.728 675
-108.892 471
-626.077 928
-1601.884 398
-1492.364 749
-1492.418 214
-1492.414 485
-516.563 206
-516.551 762
-516.492 469
-975.804 103
-109.520 571
1.980
1.960
2.181
2.148
2.457
2.473
2.478
2.479
0.37
0.79
0.36
0.40
0.52
0.44
0.51
0.47
Rh2(II)
N2
2.379
0.81
a Becke3LYP/LANL2DZ/3-21G//Becke3LYP/LANL2DZ/3-21G and Becke3LYP/LANL2DZ/6-31G*//Becke3LYP/LANL2DZ/3-21G with LANL2DZ
on Rh; 1 au ) 627.5 kcal/mol. b Natural Population Analysis Wiberg NBO bond orders; see ref 47.
Numerous initial attempts were made to find local minima
for singlet carbene 50 and the esterified analogue 53 (Me2NCO-
C((CH2)2)-CO-C:-CO2Et, Figure 2). The structures have a great
propensity for spontaneous cyclization to the corresponding
ylides in the computer. Ultimately, we located conformations
in which the dimethylamide moieties were unable to coordinate
with the carbene carbon without passing over a moderate
torsional barrier. The local minimum for 53 is depicted in Figure
2 along with the corresponding planar carbonyl ylide 52.
Truncated singlet carbene 50 is found to be 44.4 kcal/mol higher
in energy than ammonium ylide 48 (Table 1). A similar energy
Figure 1. The Becke3LYP/6-31G* optimized geometry of N-acyl
differential was found for the esterified pair 51 and 53 (52.5
ammonium ylide 29 compared with the X-ray structure (refs 22 and
kcal/mol; 6-31G*), reinforcing the idea that ester removal does
40); bond lengths (Å) to the left; selected bond angles (deg) to the
not alter the semiquantitative picture in the present series.
right; X-ray values in parentheses.
The optimized structure for diazo ketone 43 is unexceptional.
Complexes 44 and 45, however, are portrayed in Figure 3.
the largest variation being 1.6°. Optimization with the 3-21G
basis set yields a corresponding set of values that are about
twice as large: 0.022 Å, 1.6°, and 3.4°, respectively.
Formation of the former, derived from combination of diazo
ketone 43 and Rh2(II), is symbolized in Figure 4. In the reaction
of 43, shortening of the N-N bond is accompanied by
lengthening of both the C-N and Rh-Rh bonds as complex-
ation takes place. The parenthesized NBO bond orders follow
the same trend. Clearly the sp2 diazo carbon has served as a
nucleophile in its transformation to a sp3 center in 44. Loss of
nitrogen to give rhodium carbenoid 45 is complemented by
rehybridization of the former diazo carbon back to sp2 (Figures
3 and 4). The overall geometry, e.g., Rh-C and Rh-Rh bond
lengths and bond orders, is precisely what is to be expected for
a RhRhC train in which a weak Rh-C single bond in 44 has
been converted into a somewhat stronger single bond with dual
character in 45. That is, the carbenoid Rh-C connection is
characterized by a nearly equal mix of C to Rh σ dative bonding
and Rh to C π dative bonding.27 The latter was foreshadowed
by a number of previous investigations,44b,49 although the
classical Rh-C σ/π scheme differs considerably from our
double “half-bond” model. Accompanying Rh-C bond strength-
ening from 43 to 44 is Rh-Rh bond weakening. Although
negative charge resides entirely on the bridging carboxylates,
the metal positive charge drops 1% at Rh-C and 23% at the
distal rhodium center in the transformation from Rh2(II) to 45.
A summary of the 6-31G* energies and selected bond lengths
for the DFT/3-21G-refined structures in Scheme 1 is given in
Table 1. The experimental work described above, in particular
the Rh(II) tetraacetate catalyzed decomposition of diazo sub-
strates in the absence of dipolarophile, strongly suggests that
ammonium ylides are more stable than their carbonyl ylide
isomers. In complete agreement, N-ylide 48 is found to be 7.2
kcal/mol lower in energy than O-ylide 49. Given that the ester
group in 51 and 52 was replaced with hydrogen in the latter
structures and in the corresponding Rh2(II) complexes in Scheme
1 for the sake of computational economy, we checked to see if
this substitution alters the energetic relationship.
It does not. N-Ylide 51 is 11.7 kcal/mol more stable than
O-ylide 52 at the Becke3LYP/6-31G* level. The same obtains
for urea intermediate N-29 by comparison with O-31. The latter
is calculated to be 12.6 kcal/mol higher in energy with the
Becke3LYP/6-31+G* basis set. We surmise that the basis for
the higher energy of the carbonyl ylide lies in the ability of the
dimethylamino group to conjugate with CdO+ in 52. Although
the resonance structure to the right delocalizes π-electrons by
a means unavailable to 51, the same structure separates the
positive and negative charges over an additional two bonds. The
latter would appear to be the dominating energetic effect.48
(48) Although charge delocalization by resonance is an energy-lowering
effect, this notation strictly applies to singly charged systems. Zwitterionic
systems, supporting two oppositely charged centers, need to accommodate
both charge delocalization and charge separation. The former stabilizes;
the latter destabilizes.
(49) (a) Drago, R. S.; Tanner, S. P.; Richman, R. M.; Long, J. R. J. Am.
Chem. Soc. 1979, 101, 2897. Drago, R. S.; Long. J. R.; Cosmano, R. Inorg.
Chem. 1981, 20, 2920. (b) King, R. B.; King, A. D., Jr.; Iqbal, M. Z. J.
Am. Chem. Soc. 1979, 101, 4893. Drago, R. S. Inorg. Chem. 1982, 21,
1697. Dennis, A. M.; Howard, R. A.; Bear, J. L. Inorg. Chim. Acta 1982,
66, L31. Chavan, M. Y.; Ahsan, M. Q.; Lifsey, R. S.; Bear, J. L.; Kadish,
K. M. Inorg. Chem. 1986, 25, 3218. Eagle, C. T.; Farrar, D. G.; Pfaff, C.
U. Organometallics 1998, 17, 4523;

+
Rh(II)-Catalyzed Equilibration of CO and NH4 Ylides
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8161
Figure 2. Becke3LYP/3-21G optimized geometries for carbonyl ylide 52 and singlet carbene 53.
Figure 3. Becke3LYP/3-21G optimized geometries for the initial catalytic complex 44 (from diazo ketone 43 and Rh2(II)) and the subsequent
rhodium carbenoid 45 resulting from loss of N2.
contribution to the C-Rh bond is dative bonding by a lone
electron pair on carbon; i.e., a C-LP (σ*(Rh-Rh) interaction.
At the same time, however, the C-Rh bond lengths in 46 and
47 are considerably longer than that in 44. This can be
understood as a molecular response to significant steric effects
between the five-membered rings and the Rh2(II) cage. Ring
closure brings the oxygens of the dirhodium tetraformate moiety
Figure 4. Symbolic coupling of 43 and Rh2(II) to give 44 and the
subsequent loss of dinitrogen to produce 45. Bond lengths in Å are
given beside the reactive bonds; bond orders are shown in parentheses;
in close proximity to both hydrogens and heavy atoms of the
pendant rings. Nonetheless, as will be discussed below, com-
plexes 46 and 47 are the two most stable species among those
considered in Scheme 1. A balance of forces is obviously at
work. Steric effects destabilize the complexes, but the formation
of a new bond as a result of ring closure more than compensates
for the compression effect. The mark of the compromise is the
stretched C-Rh bond distances.
The DFT Energy Profile. The goals of the present work
are 3-fold. First we seek to establish the existence of the various
species as genuine intermediates residing in well-defined energy
wells as described above. Second, we want to understand the
energy relationships along the pathway, at the very least, in a
semiquantitative sense. Third, we hope to lay a general
mechanistic foundation for the function of the dirhodium
tetracarboxylate(II) catalyst to stimulate further experimentation
and theoretical evaluation. This section focuses on the second
and third goals. Figure 6 compiles and compares the energy
relationships. In the present work, no transition states have been
examined explicitly. We have, however, depicted the elimination
of dinitrogen from 44 as rate determining (Ea ∼ 10 kcal/mol)
in accord with the kinetic studies of Pirrung and Morehead.45
The fact that the intermediates are high above product ground
NBO charges at rhodium are reported above the atoms.
Thus, the distal metal center serves as an electron sink to
accommodate polarization of the Rh-Rh bond in both complex
44 and carbenoid 45. That the influence of the distal rhodium
atom in RhRhC appears to be a decisive factor in catalysis is
entirely consistent with early studies by Drago,49a,c the inhibition
work of Pirrung and Morehead,46 and the more recent applica-
tion of a novel series of dirhodium(II) catalysts to 1-diazo-5-
penten-2-one cyclization by Lahuerta and co-workers.50
The final structures to be considered are the ylide-Rh2(II)
complexes 46 and 47 (Figure 5) formed by ambident cyclization
onto the carbenoid carbon of 45, either by the lone electron
pair on the amide nitrogen or that on the amide carbonyl,
respectively. To a large degree, the C-Rh σ-bonds in 46 and
47 should resemble that for complex 44. In both cases, an
anionic center is formed in the corresponding ylides 48 and 49
upon subsequent dissociation. Indeed, Table 1 shows the C-Rh
and Rh-Rh bond orders to be similar for the three complexes.
NBO analysis concurs. In all three cases the overwhelming
(50) Lahuerta, P.; Pe´rez-Pieto, J.; Stiriba, S.-E.; Ubeda, M. A. Tetrahe-
dron Lett. 1999, 40, 1751.

8162 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Padwa et al.
Figure 5. Becke3LYP/3-21G optimized geometries for the complexes (46, and 47) between Rh2(II) and the five-membered ring 1,3-dipoles 48 and
49, respectively.
calculated to be 12.6 kcal/mol (6-31+G*) more stable than the
corresponding O-ylide 31.
A second interesting point depicted by Figure 6 is the
importance of diazoketone 43 as a substrate for the process.
The high energy of the diazoketone moiety places it only 3.5
kcal/mol below O-ylide 49 (+ N2). The starting materials are
consequently located at an ideal entry point on the energy
surface to deliver the key complex 45 exergonically. A third
and general characteristic of the energy scheme is its profiling
of the action of the rhodium tetracarboxylate catalyst. Two
important roles are played by the organometallic reagent. First
and foremost the compound serves to keep the reaction
intermediates (i.e., 44-47) at energies that permit product
formation under mild conditions. The ultimate zwitterionic
reactants 48 and 49 are formed by strongly exergonic ring
closure at the rhodium carbenoid carbon followed by regenera-
tion of the Rh(II) catalyst in preference to reopening of the rings.
Insight into these final two steps is gained by examining the
concomitant structural changes at the reacting carbon center.
Optimized carbenoid 45 sustains a relatively short Rh-C bond
length of 1.960 Å and an NBO bond order of bo ) 0.79. As
alluded to above, these values are comparable to those derived
for the simpler [Rh2(II)]-CH2 system: 1.920 Å and bo ) 0.98.27
Figure 6. Energy diagram for rhodium(II) catalytic pathway. The
6-31G* energies are in kcal/mol; 3-21G energies are in parentheses.
During cyclization to 46 and 47, the Rh-C bonds lengthen by
0.22 and 0.19 Å and thereby weaken substantially; bo ) 0.36
The value of 10* kcal/mol has been taken from ref 46. N2 in (45 +
and 0.40, respectively (Table 1). Consequently, the stretched
N2) correlates only with 44 and (43 + Rh2(II)). Rh2(II) refers to the
tetraformate structure given in Scheme 1.
metal-carbon bonds offer only moderate resistance to dissocia-
tive cleavage (32-37 kcal/mol, Figure 6).
The second role played by Rh2(RCO2)4 concerns initiation
of the diazo carbonyl chemistry. Coordination to 43 to give
intermediate 44 sets up the original diazoketone for dinitrogen
loss without the need to employ harsh reaction conditions (i.e.,
heat or light). Clearly the end-game zwitterions 48 and 49 can
be generated directly from carbene 50. However, were it
necessary to take this route instead of passing through complex
45, the additional energy cost is estimated to be around 40-50
kcal/mol. Thus, the dirhodium tetracarboxylate triggers diazo
ketone decomposition and maintains it under highly controlled
conditions at relatively low energies as expected for an efficient
catalyst.
states (e.g., 46 and 47 as well as the ultimate isolated
cycloaddition and rearrangement products) suggests that the
barriers can be readily surmounted in accord with Hammond’s
postulate.
The first revealing feature of the energy diagram in Figure 6
is that the rhodium tetraformate complexed ylides 46 and 47
reside in energy basins; this occurs despite significant intramo-
lecular steric effects. Furthermore, complex 46 is favored by
2.3 kcal/mol over the isomeric carbonyl ylide complex 47.
Combined with the prediction that ammonium ylide 48 is
likewise stabilized by 7.2 kcal/mol relative to O-ylide 49, the
result implies that for a fully equilibrated system the dissociation
of complex 46 to N-ylide 48 is predicted to be 4.9 kcal more
facile than the release of O-ylide 49 from complex 47. This
picture is fully consistent with the thermodynamically controlled
formation of ammonium ylide-rearranged products obtained
from cyclopropyl diazo amides under the influence of dirho-
dium(II) tetraacetate. It likewise comports with the isolation of
nitrogen ylide 29 in the urea series where the N-ylide is
Conclusions
The experiments described in the first section of this report
fall into four categories: (1) a potent dipolarophile such as
DMAD reacts with diazo keto substrates in the presence of Rh2-
(OAc)4 to capture carbonyl ylides such as 31, 39, and 49 in
excellent yields; (2) a weaker trapping agent such as N-

+
Rh(II)-Catalyzed Equilibration of CO and NH4 Ylides
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8163
CDCl3) δ 1.13 (t, 3H, J ) 6.9 Hz), 1.20 (s, 2H), 1.34 (s, 2H), 3.31 (s,
3H), 3.82 (q, 2H, J ) 6.9 Hz), 7.21 (m, 3H), and 7.35 (m, 2H); 13C
NMR (75 MHz, CDCl3) δ 13.9, 14.1, 17.3, 30.0, 38.3, 61.1, 127.3,
127.4, 129.1, 143.2, 168.2, and 170.7. Anal. Calcd for C14H17NO3: C,
67.98; H, 6.93; N, 5.67. Found: C, 67.81; H, 6.92; N, 5.53.
phenylmaleimide routinely elicits lower yields of cycloadduct
and increasing quantities of rearranged lactam; (3) in the absence
of a dipolarophile, the rhodium(II) catalyst promotes exclusive
formation of lactam; and (4) ammonium ylide 29 in the presence
of Rh2(OAc)4 and DMAD yields 10% of furan 33 derived from
the carbonyl ylide intermediate.
A solution containing 8.0 g (32 mmol) of the above ester in 60 mL
of ethanol was treated with 32 mL (97 mmol) of an aqueous 3 M KOH
solution, and the resulting mixture was stirred at room temperature for
4 h. The solution was concentrated under reduced pressure, water was
added, and the mixture was acidified with an aqueous 1 N HCl solution
and extracted with ether. The combined ether extracts were dried over
MgSO4, and the solvent was removed under reduced pressure to give
6.0 g (85%) of 1-(methylphenylcarbamoyl)cyclopropanecarboxylic acid
as a white solid: mp 140-141 °C; IR (neat) 3000, 1716, 1645, 1381,
and 1175 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.30 (m, 4H), 3.31 (s,
3H), 7.30 (m, 2H), 7.35 (m, 3H), and 10.27 (s, 1H); 13C NMR (75
MHz, CDCl3) δ 18.0, 18.1, 29.8, 38.5, 127.4, 127.6, 129.3, 143.0, 167.8,
and 176.7. Anal. Calcd for C12H13NO3: C, 65.73; H, 5.98; N, 6.39.
Found: C, 65.46; H, 5.81; N, 6.27.
These observations reflect a catalyst-promoted system of
equilibria with a clear-cut thermodynamic bias. In the case of
the cyclopropyl diazo keto amides, if we assume that DMAD
trapping of carbonyl ylide is faster than rearrangement of
ammonium ylide but that N-phenylmaleimide is competitive
with it, Scheme 1 and Figure 6 explain observations (1) and
(2) as arising from a rapidly established equilibrium between
ylides 48 and 49. Slower cycloaddition to 49 provides the
thermodynamically more stable N-ylide 48 an opportunity for
intramolecular transposition. In the presence of rhodium catalyst
alone, the energetically favored 48 provides the sole reaction
channel to products accounting for observation (3). In the case
of diazoacetyl ureas (e.g., 28), we believe the energy profile of
Figure 6 also obtains. The low yield of furan 33 in observation
(4) is readily accommodated by the competition of N-ylide 29
for DMAD, a reaction course not taken by cyclopropyl
intermediates such as 48 and 51. For the latter, the out-of-plane
N-CH3 and cyclopropyl carbons may well block effective
approach by the acetylene to the carbanionic center.
For all of the reactions examined here, the nuances in relative
stabilities and barrier heights will, of course, vary depending
on substituents and ring constraints in the diazo ketone substrates
as found, for example, for compounds 1, 4, and 40. Given that
the rhodium(II)-catalyzed reactions were carried out in the
aromatic solvents benzene and toluene, solvation effects may
also be important. Benzene is known to form a 2:1 adduct with
dirhodium(II) tetracarboxylates.45a Since the role of solvent has
not been included in our calculations, some of the energy
relationships might vary if aromatic π solvation were taken into
account. Finally, the energy surfaces reflected by Figure 6 are
certain to be modified by variations in the ligands bridging the
Rh(II) atoms of the catalyst.43 In future contributions we will
address this issue as well as questions of stereochemical control.
To a solution containing 4.4 g (34 mmol) of 2-carboethoxyacetic
acid in 50 mL of CH2Cl2 at 0 oC was slowly added 34 mL (67 mmol)
of isopropylmagnesium chloride, and the reaction mixture was stirred
at 0 oC for 30 min. The solution was heated at 40 °C for an additional
30 min. In a separate flask, 4.0 mL (46 mmol) of oxalyl chloride and
2 drops of DMF were slowly added to a solution of 4.48 g (30 mmol)
of 1-(methylphenylcarbamoyl)cyclopropanecarboxylic acid in 50 mL
of CH2Cl2. The solution was allowed to stir for 2 h at room temperature
and was concentrated under reduced pressure. The residue was taken
up in 5 mL of CH2Cl2, and the mixture was added to the magnesium
dianion solution. The resulting solution was stirred at 0 °C for 1 h and
was then quenched with 50 mL of 50% HCl. The solution was extracted
with CH2Cl2 and dried over MgSO4. Purification of the crude residue
by silica gel chromatography afforded 3.94 g (47%) of 3-[1-(meth-
ylphenylcarbamoyl)cyclopropyl]-3-oxopropionic acid ethyl ester as a
1
clear oil: IR (neat) 1737, 1694, 1645, and 1374 cm-1; H NMR (300
MHz, CDCl3) δ 1.2-1.5 (m, 7H), 3.33 (s, 3H), 3.36 (s, 2H), 4.10 (q,
2H, J ) 7.1 Hz), and 7.2-7.4 (m, 5H); 13C NMR (75 MHz, CDCl3) δ
13.9, 14.0, 14.1, 18.1, 38.6, 40.6, 46.0, 127.2, 127.3, 127.4, 127.5, 127.8,
129.6, 142.5, 166.6, and 184.8. Anal. Calcd for C16H19NO4: C, 66.41;
H, 6.62; N, 4.84. Found: C, 66.32; H, 6.39; N, 4.73.
2-Diazo-3-[1-(methylphenylcarbamoyl)cyclopropyl]-3-oxopropi-
onic Acid Ethyl Ester (10). To a stirred solution of 1.3 g (4.5 mmol)
of the above amide in 10 mL of CH3CN at 0 °C was added 1.5 mL
(10.8 mmol) of Et3N. The reaction mixture was stirred for 30 min at 0
°C, and then 1.1 g (5.4 mmol) of tosyl azide was added in one portion
and stirring was continued for an additional 12 h. The solvent was
removed under reduced pressure, and the crude oil was purified by
silica gel chromatography to give 1.0 g (73%) of 10 as a yellow solid,
Experimental Section
Melting points are uncorrected. Mass spectra were determined at an
ionizing voltage of 70 eV. Unless otherwise noted, all reactions were
performed in flame-dried glassware under an atmosphere of dry
nitrogen. Solutions were evaporated under reduced pressure with a
rotary evaporator, and the residue was chromatographed on a silica
gel column using an ethyl acetate-hexane mixture as the eluent unless
specified otherwise.
1
mp 64-65 °C: IR (neat) 2128, 1723, 1687, and 1367 cm-1; H NMR
(300 MHz, CDCl3) δ 1.34 (m, 5H), 1.71 (m, 2H), 3.30 (s, 3H), 4.31
(q, 2H, J ) 7.1 Hz), 7.14 (d, 2H, J ) 7.4 Hz), 7.35 (d, 2H, J ) 7.4
Hz), and 7.3-7.4 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 14.4, 14.5,
17.6, 35.9, 38.6, 61.8, 76.3, 126.4, 127.5, 127.8, 129.1, 129.6, 142.7,
161.1, 169.3, and 185.4. Anal. Calcd for C16H17N3O4: C, 60.93; H,
5.44; N, 13.33. Found: C, 60.85; H, 5.28; N, 13.17.
3-[1-(Methylphenylcarbamoyl)cyclopropyl]-3-oxopropionic Acid
Ethyl Ester. To a solution containing 9.5 g (60 mmol) of 1,1-
cyclopropanecarboxylic acid monoethyl ester51 in 150 mL of CH2Cl2
and a catalytic amount of DMF was added 15.7 mL (180 mmol) of
oxalyl chloride dropwise at room temperature. The mixture was stirred
for 3 h at room temperature, and the excess oxalyl chloride and the
solvent were removed under reduced pressure. The crude residue was
dissolved in 100 mL of CH2Cl2. To this solution was added a solution
containing 7.7 g (72 mmol) of N-methylaniline, and the mixture was
stirred for 4 h at room temperature. The solution was washed with a
saturated aqueous NaHCO3 solution followed by brine. The organic
layer was separated and dried over MgSO4, and the solvent was
removed under reduced pressure. The crude residue was purified by
silica gel chromatography to give 8.0 g (54%) of ethyl 1-(methylphen-
ylcarbamoyl)cyclopropane carboxylate as a white solid: mp 44-45
°C; IR (neat) 1716, 1638, 1303, and 1175 cm-1; 1H NMR (300 MHz,
Dimethyl 5-Carboethoxy-5,8-epoxy-8-(methylphenylcarbamoyl)-
4-oxo-6-spiro[2.5]octene-6,7-dicarboxylate (11). To a solution con-
taining 0.7 mL (5.9 mmol) of dimethyl acetylenedicarboxylate and 2
mg of rhodium(II) acetate in 5 mL of refluxing benzene was added
dropwise 0.35 g (1.2 mmol) of diazo amide 10. The reaction mixture
was heated at reflux for 30 min, and the solution was concentrated
under reduced pressure. The resulting residue was purified by silica
gel chromatography to give 0.45 g (87%) of 11 as a yellow solid: mp
1
134-135 °C; IR (neat) 1773, 1723, 1488, and 1282 cm-1; H NMR
(300 MHz, CDCl3) δ 1.04 (m, 2H), 1.32 (t, 3H, J ) 7.2 Hz), 1.35 (m,
2H), 3.26 (s, 3H), 3.41 (s, 3H), 3.81 (s, 3H), 4.28 (q, 2H, J ) 7.2 Hz),
6.9-7.1 (m, 3H), and 7.2-7.3 (m, 2H); 13C NMR (75 MHz, CDCl3)
δ 14.0, 29.4, 41.5, 51.6, 52.8, 62.4, 77.4, 77.5, 116.9, 120.8, 124.0,
126.6, 128.9, 129.2, 129.3, 129.4, 145.9, 155.8, 161.5, and 168.9. Anal.
Calcd for C22H23NO8: C, 61.53; H, 5.40; N, 3.26. Found: C, 61.49;
H, 5.43; N, 3.25.
(51) Singh, R. K.; Danishefsky, S. J. Org. Chem. 1975, 40, 2969.

8164 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Padwa et al.
Spiro[7-carboethoxy-4,7-epoxy-4-(methylphenylcarbamoyl)-2-
phenyl-1,3,6-trioxopseudoisoindole-5,1′-cyclopropane] (12). To a
solution containing 1.0 g (5.9 mmol) of N-phenylmaleimide and 2 mg
of rhodium(II) acetate in 5 mL of refluxing benzene was added dropwise
0.35 g (1.2 mmol) of diazo amide 10. The reaction mixture was heated
at reflux for 30 min, and the solution was concentrated under reduced
pressure. The mixture was purified by silica gel chromatography to
give 0.23 g (42%) of 12 as a yellow solid: mp 162-163 °C; IR (neat)
128.4, 128.9, 129.3, 131.8, 146.3, 154.6, 163.6, 170.6, 170.8, and 199.9.
Anal. Calcd for C25H22N2O6: C, 67.24; H, 4.97; N, 6.28. Found: C,
67.14; H, 4.83; N, 6.17.
4-(Methylphenylamino)-5,7-dioxo-6-phenyl-3,5,6,7-tetrahydro-
2H-1-oxa-5-indacene-8-carboxylic Acid Methyl Ester (17). To a
solution of 0.04 g (0.1 mmol) of cycloadduct 15 in 2 mL of CH2Cl2
was added 2 equiv of BF3‚OEt2, and the solution was allowed to stir at
room temperature for 12 h. The mixture was poured into 2 mL of a
saturated NaCl solution and extracted with CH2Cl2. The combined
organic extracts were dried over anhydrous MgSO4 and concentrated
under reduced pressure. The residue was subjected to flash silica gel
chromatography to give 0.04 g (85%) of 17 as a colorless oil: IR (neat)
3434, 1735, 1591, and 1490 and 997 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 2.74 (t, 2H, J ) 8.9 Hz), 3.45 (s, 3H), 3.97 (s, 3H), 4.68 (t, 2H, J )
8.9 Hz), 6.77-6.91 (m, 3H), and 7.22-7.44 (m, 7H); 13C NMR (CDCl3,
75 MHz) δ 28.9, 40.4, 53.1, 73.6, 116.4, 120.4, 126.6, 127.9, 129.0,
129.3, 130.9, 131.6, 133.1, 143.7, 146.0, 163.5, 164.3, 164.6, and 164.9.
Anal. Calcd for C25H20N2O5: C, 70.07; H, 4.71; N, 6.54. Found: C,
69.86; H, 4.59; N, 6.43.
6-Phenyl-5-methyl-4,7-dioxo-5-azaspiro[2.4]heptane-6-carboxyl-
ic Acid Ethyl Ester (19). To a suspension containing 2 mg of
rhodium(II) acetate in 10 mL of benzene was added 0.5 g (1.6 mmol)
of diazoamide 10. The reaction was heated at reflux for 4 h, and the
solvent was removed under reduced pressure. The crude residue was
purified by silica gel chromatography to give 0.3 g (62%) of 19 as a
clear oil: IR (neat) 2980, 1767, 1707, 1450, and 1390 cm-1; 1H NMR
(300 MHz, CDCl3) δ 0.92 (m, 1H), 1.13 (m, 1H), 1.35 (t, 3H, J ) 7.1
Hz), 1.53 (m, 1H), 1.70 (m, 1H), 3.05 (s, 3H), 4.22 (q, 2H, J ) 7.1
Hz), 7.00 (m, 2H), and 7.23 (m, 3H); 13C NMR (75 MHz, CDCl3) δ
14.0, 20.3, 21.6, 26.8, 30.9, 36.2, 62.7, 78.0, 127.5, 128.4, 128.6, 129.9,
133.3, 166.6, 172.3, 204.0. Anal. Calcd for C16H17NO4: C, 66.87; H,
5.97; N, 4.88. Found: C, 66.81; H, 5.77; N, 4.61.
1-(Benzylmethylcarbamoyl)cyclopropanecarboxylic Acid Ethyl
Ester. To a solution containing 10.0 g (63 mmol) of 1,1-cyclopropane-
carboxylic acid monoethyl ester in 250 mL of CH2Cl2 and a catalytic
amount of DMF was added 16.5 mL (190 mmol) of oxalyl chloride
dropwise at room temperature. The mixture was stirred for 3 h at room
temperature, and the excess oxalyl chloride and CH2Cl2 were removed
under reduced pressure. The crude residue was dissolved in 250 mL
of CH2Cl2, 19.2 g (158 mmol) of N-benzylmethylamine was added,
and the mixture was stirred for 24 h at room temperature. The reaction
mixture was washed with a saturated aqueous NaHCO3 solution and
brine and dried over MgSO4, and the solvent was removed under
reduced pressure to give 16.1 g (98%) of 1-(benzylmethylcarbamoyl)-
cyclopropanecarboxylic acid ethyl ester as a yellow oil: IR (neat) 1732,
1651, 1304, 1178, and 1028 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.15
(t, 3H, J ) 7.1 Hz), 1.34 (m, 2H), 1.47 (m, 2H), 2.89 (s, 3H), 4.11 (q,
2H, J ) 7.1 Hz), 4.58 (s, 2H), and 7.30 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 13.8, 16.1, 18.7, 28.7, 34.4, 50.8, 61.3, 127.0, 127.6, 128.2,
136.6, 168.2, and 171.1; HRMS calcd for C15H19NO3 261.1365, found
261.1368.
1-(Benzylmethylcarbamoyl)cyclopropanecarboxylic Acid. A solu-
tion containing 16 g (61 mmol) of the above ester in 150 mL of ethanol
was treated with 3.4 g (61 mmol) of KOH, and the resulting mixture
was stirred at room temperature for 24 h. The reaction mixture was
concentrated under reduced pressure, and water was added. The solution
was acidified with an aqueous 1 N HCl solution and was extracted
with ether. The combined organic layer was dried over MgSO4, and
the solvent was removed under reduced pressure to give 5.8 g (41%)
of 1-(benzylmethylcarbamoyl)cyclopropanecarboxylic acid as a yellow
oil: IR (neat) 3473, 1732, 1644, 1321, 1206, and 1162 cm-1; 1H NMR
(300 MHz, CDCl3) δ 1.72 (m, 2H), 1.78 (m, 2H), 3.10 (s, 3H), 4.58
(s, 2H), 7.28 (m, 5H), and 11.78 (s, 1H); 13C NMR (75 MHz, CDCl3)
δ 13.6, 21.5, 21.9, 24.3, 62.6, 127.3, 127.8, 128.5, 138.0, 171.7, and
175.3; HRMS calcd for C13H15NO3 233.1052, found 233.1049.
3-[1-Benzylmethylcarbamoyl)cyclopropyl]-3-oxopropionic Acid
Ethyl Ester. To a solution containing 2.5 g (19 mmol) of 2-carboeth-
oxyacetic acid in 160 mL of THF at 0 °C was slowly added 19 mL
(38 mmol) of isopropylmagnesium chloride, and the reaction mixture
was stirred at 0 °C for 30 min. In a separate flask, a mixture containing
2.8 mL (32 mmol) of oxalyl chloride and 2 drops of DMF was slowly
1
1744, 1701, and 1495 cm-1; H NMR (300 MHz, CDCl3) δ 1.1-1.3
(m, 2H), 1.36 (t, 3H, J ) 7.2 Hz), 1.68 (m, 2H), 3.49 (s, 3H), 3.72 (d,
1H, J ) 7.4 Hz), 3.95 (d, 1H, J ) 7.4 Hz), 4.43 (q, 2H, J ) 7.2 Hz),
6.8-6.9 (m, 3H), and 7.2-7.4 (m, 7H); 13C NMR (75 MHz, CDCl3)
δ 14.1, 14.2, 20.0, 28.4, 33.7, 43.2, 60.4, 63.7, 76.6, 112.3, 116.2, 116.9,
121.1, 126.6, 128.4, 128.9, 129.2, 131.8, 163.7, 170.1, 170.8, and 200.0.
Anal. Calcd for C26H24N2O6: C, 67.82; H, 5.25; N, 6.08. Found: C,
67.74; H, 5.30; N, 6.01.
2-Diazo-3-[1-methylphenylcarbamoyl)cyclopropyl]-3-oxopropi-
onic Acid Methyl Ester (13). To a 1.0 g (4.6 mmol) sample of
1-(methylphenylcarbamoyl)-cyclopropanecarboxylic acid in 25 mL of
CH2Cl2 were added 0.7 g (7.0 mmol) of oxalyl chloride and 1 drop of
DMF. The solution was allowed to stir at room temperature for 30
min and was concentrated under reduced pressure to remove the excess
oxalyl chloride. The residue was taken up in 1 mL of CH2Cl2, and this
solution was added slowly to 10 mL of a 0.5 M THF solution of the
magnesium dianion of hydrogen ethyl malonate at 0 °C. The solution
was allowed to stir for 1 h and was then quenched with a 1 N HCl
solution. The reaction was extracted with ether, and the ether extracts
were dried over anhydrous MgSO4 and concentrated under reduced
pressure. The residue was subjected to flash silica gel chromatography
to give 0.96 g (76%) of 3-[1-methylphenylcarbamoyl]-3-oxopropionic
acid methyl ester as a yellow oil: IR (neat) 2960, 1720, 1637, and
1
1340 cm-1; H NMR (CDCl3, 300 MHz) δ 1.20-1.36 (m, 4H), 3.31
(s, 3H), 3.36 (s, 2H), 3.63 (s, 3H), and 7.14-7.36 (m, 5H); 13C NMR
(CDCl3, 75 MHz) δ 18.1, 38.5, 38.6, 45.7, 52.3, 127.3, 127.8, 129.6,
142.5, 167.0, and 168.5. Anal. Calcd for C15H17NO4: C, 65.44; H, 6.22;
N, 5.09. Found: C, 65.31; H, 6.13; N, 5.17.
Standard diazo transfer afforded 13 (91%) as a labile yellow oil
which was immediately subjected to the rhodium(II)-catalyzed reac-
1
tion: IR (neat) 2135, 1723, 1637, and 1368 cm-1; H NMR (CDCl3,
300 MHz) δ 1.20-1.40 (m, 2H), 1.61-1.68 (m, 2H), 3.26 (s, 3H),
3.81 (s, 3H), and 7.09-7.35 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ
17.6, 35.9, 38.5, 52.4, 125.8, 127.6, 129.1, 142.6, 161.5, 169.2, and
185.2.
4,7-Epoxy-4-(methylphenylamino)-8-oxospiro[2.5]oct-5-ene-5,6,7-
tricarboxylic Acid Trimethyl Ester (14). To a mixture of 2 mg of
rhodium(II) acetate and 40 µL (0.35 mmol) of dimethyl acetylenedi-
carboxylate in 2 mL of benzene at 80 °C was added 0.05 g (0.17 mmol)
of diazo amide 13 in 0.5 mL of benzene over a period of 5 min. The
solution was heated at 80 °C for 1 h and concentrated under reduced
pressure. The residue was subjected to flash silica gel chromatography
to give 0.6 g (87%) of 14 as a yellow oil: IR (neat) 2940, 1737, 1694,
1
1467, and 1374 cm-1; H NMR (CDCl3, 300 MHz) δ 1.03 (dd, 2H, J
) 7.1 and 5.3 Hz), 1.35 (dd, 2H, J ) 7.1 and 5.3 Hz), 3.26 (s, 3H),
3.42 (s, 3H), 3.82 (s, 3H), 3.83 (s, 3H), and 6.96-7.31 (m, 5H); 13C
NMR (CDCl3, 75 MHz) δ 29.4, 41.7, 51.6, 52.9, 53.0, 109.8, 121.0,
124.2, 128.4, 129.3, 129.4, 138.4, 145.8, 155.8, 161.9, 164.3, 166.1,
and 168.9. Anal. Calcd for C21H21NO8: C, 60.72; H, 5.10; N, 3.37.
Found: C, 60.58; H, 5.05; N, 3.24.
4′,7′-Epoxy-7′-carbomethoxy-4′-(methylphenylamino)-2′-phenyl-
1′,3′,6′-trioxospiro[1,5′-cyclopropane-1′,3′,3a′,4′,5′,6′,7′,7a′-octahy-
droisoindole (15). To a solution of 0.06 g (0.35 mmol) of N-phenyl-
maleimide and 2 mg of rhodium(II) acetate in 1 mL of benzene at 80
°C was added 0.05 g (0.17 mmol) of diazo amide 13 in 0.5 mL of
benzene over a period of 10 min. The reaction was allowed to stir at
80 °C for 2 h, cooled to room temperature, and concentrated under
reduced pressure. The residue was subjected to flash silica gel
chromatography to give 0.06 g (80%) of 15 as a white solid: mp 203-
204 °C; IR (KBr) 1751, 1698, 1591, and 1490 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.25-1.76 (m, 4H), 3.50 (s, 3H), 3.97 (s, 3H), 4.19 (s,
1H), 4.40 (s, 1H), 6.83-7.43 (m, 10 H); 13C NMR (CDCl3, 75 MHz)
δ 20.1, 28.5, 33.7, 43.3, 46.7, 54.0, 112.1, 116.9, 117.0, 121.2, 126.5,

+
Rh(II)-Catalyzed Equilibration of CO and NH4 Ylides
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8165
added to a solution of 3.7 g (16 mmol) of 1-(benzylmethylcarbamoyl)-
cyclopropane carboxylic acid in 160 mL of CH2Cl2. The solution was
allowed to stir for 2 h at room temperature and was then concentrated
under reduced pressure, the residue was taken up in 5 mL of THF, and
the mixture was added to the above magnesium dianion solution. The
resulting mixture was stirred at 0 °C for 1 h and was then quenched
with 50 mL of 50% HCl. The solution was extracted with ether, dried
over MgSO4, and chromatographed on a silica gel column to give 1.9
g (42%) of 3-[1-benzylmethylcarbamoyl)cyclopropyl]-3-oxopropionic
acid ethyl ester as a clear oil: IR (neat) 1743, 1694, 1650, 1243, and
purified by silica gel chromatography to give 0.9 g (60%) of 23 as a
clear oil: IR (neat) 1756, 1716, 1689, 1372, and 1123 cm-1; 1H NMR
(300 MHz, CDCl3) δ 1.24 (m, 1H), 1.34 (t, 3H, J ) 7.1 Hz), 1.56 (m,
2H), 1.71 (m, 1H), 2.83 (s, 3H), 4.05 (s, 1H), 4.37 (m, 3H), 4.49 (d,
1H, J ) 15 Hz), 4.63 (d, 1H, J ) 15 Hz), 7.16 (m, 2H), 7.30 (m, 6H),
and 7.42 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 13.9, 14.5, 27.5, 34.5,
40.2, 47.8, 60.1, 63.5, 76.5, 100.8, 126.7, 127.6, 127.9, 128.2, 128.7,
128.9, 132.2, 137.3, 157.8, 164.5, 170.2, 171.2, and 200.2. Anal. Calcd
for C27H26N2O6: C, 68.33; H, 5.53; N, 5.91. Found: C, 68.31; H, 5.42;
N, 5.86.
1-Diethylcarbamoylcyclopropanecarboxylic Acid Ethyl Ester. To
a solution containing 10 g (63 mmol) of 1,1-cyclopropanecarboxylic
acid monoethyl ester in 250 mL of CH2Cl2 and a catalytic amount of
DMF was added 16.5 mL (190 mmol) of oxalyl chloride dropwise at
room temperature. The mixture was stirred for 3 h at room temperature,
and the excess oxalyl chloride and solvent were removed under reduced
pressure. The crude residue was dissolved in 250 mL of CH2Cl2, 11.5
g (158 mmol) of diethylamine was added, and the mixture was stirred
for 24 h at room temperature. The reaction mixture was washed with
saturated aqueous NaHCO3 and brine and dried over MgSO4, and the
solvent was removed under reduced pressure to give 13 g (96%) of
1-diethylcarbamoylcyclopropanecarboxylic acid ethyl ester as a yellow
oil: IR (neat) 1725, 1643, 1307, and 1182 cm-1; 1H NMR (300 MHz,
CDCl3) δ 1.02 (m, 11H), 1.22 (m, 2H), 3.19 (t, 4H, J ) 6.9 Hz), and
3.94 (q, 2H, J ) 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 11.1, 11.6,
12.4, 13.1, 14.8, 28.0, 38.3, 40.8, 60.5, 166.5, and 170.6; HRMS calcd
for C11H19NO3 213.1364, found 213.1362.
1
1029 cm-1; H NMR (300 MHz, CDCl3) δ 1.18 (t, 3H, J ) 7.1 Hz),
1.40 (m, 2H), 1.52 (m, 2H), 2.88 (s, 3H), 3.41 (s, 2H), 4.10 (m, 2H),
4.56 (s, 2H), and 7.24 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 13.9,
17.2, 34.6, 37.7, 45.3, 51.2, 53.3, 61.3, 127.5, 128.0, 128.5, 136.3, 166.5,
168.5, and 198.4. Anal. Calcd for C17H21NO4: C, 67.29; H, 6.98; N,
4.62. Found: C, 67.05; H, 6.87; N, 4.60.
3-[1-(Benzylmethylcarbamoyl)cyclopropyl]-2-diazo-3-oxopropi-
onic Acid Ethyl Ester (20). To a solution containing 1.3 g (4.2 mmol)
of the above ester in 25 mL of CH2Cl2 was added 1.17 mL (8.4 mmol)
of triethylamine, and the resultant mixture was stirred for 30 min at 0
°C. At the end of this time, 0.63 mL (5 mmol) of mesyl azide was
added dropwise over a period of 15 min and the mixture was stirred
for an additional 24 h. The reaction was quenched with 10% NaOH
and extracted with CH2Cl2. Silica gel chromatography of the crude
reaction mixture afforded 1.2 g (92%) of 20 as a yellow oil which
decomposed on standing and was immediately subjected to the
rhodium(II)-catalyzed reaction: IR (neat) 3064, 2135, 1729, 1695, 1647,
1
and 1308 cm-1; H NMR (300 MHz, CDCl3) δ 1.25 (t, 3H, J ) 7.2
1-Diethylcarbamoylcyclopropanecarboxylic Acid. A solution con-
taining 13 g (60 mmol) of the above oil in 125 mL of ethanol was
treated with 3.3 g (60 mmol) of KOH, and the resulting mixture was
stirred at room temperature for 24 h. The reaction mixture was
concentrated under reduced pressure, water was added, and the solution
was acidified with an aqueous 1 N HCl solution and extracted with
ether. The combined organic extracts were dried over MgSO4, and the
solvent was removed under reduced pressure to give 4.9 g (45%) of
1-diethylcarbamoylcyclopropanecarboxylic acid as a yellow oil: IR
Hz), 1.44 (m, 4H), 2.80 (s, 3H), 4.21 (q, 2H, J ) 7.2 Hz), 4.45 (s,
2H), and (m, 5H); 13C NMR (75 MHz, CDCl3) δ 13.8, 13.9, 14.7, 34.6,
35.4, 51.6, 61.3, 77.2, 127.0, 127.8, 128.2, 136.5, 160.0, 168.5, and
186.2.
Dimethyl 5-Carboethoxy-5,8-epoxy-8-(benzylmethylcarbamoyl)-
4-oxo-6-spiro[2,5]octene-6,7-dicarboxylate (21). To a solution con-
taining 0.06 mL (0.46 mmol) of dimethyl acetylenedicarboxylate and
2 mg of rhodium(II) acetate in 10 mL of refluxing benzene was added
0.1 g (0.30 mmol) of diazo amide 20 dropwise over 20 min. The
reaction mixture was heated for an additional 1 h, and the solvent was
removed under reduced pressure. The crude mixture was purified by
silica gel chromatography to give 0.8 g (57%) of 21 as a yellow solid:
mp 108-109 °C; IR (KBr) 3062, 1772, 1726, 1693, 1600, 1270, 1243,
and 1045 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.91 (m, 1H), 1.07 (m,
1H), 1.31 (t, 3H, J ) 7.1 Hz), 1.50 (m, 1H), 1.73 (m, 1H), 2.92 (s,
3H), 3.66 (s, 3H), 3.79 (s, 3H), 4.26 (m, 2H), 4.37 (d, 1H, J ) 16 Hz),
5.21 (d, 1H, J ) 16 Hz), 7.16 (m, 2H), and 7.32 (m, 3H); 13C NMR
(75 MHz, CDCl3) δ 14.0, 14.4, 15.0, 28.6, 30.8, 43.7, 51.6, 52.7, 53.4,
58.8, 62.0, 104.9, 126.6, 127.8, 129.0, 135.7, 156.9, 165.1, 167.2, 168.3,
and 206.8. Anal. Calcd for C23H25NO8: C, 62.30; H, 5.68; N, 3.16.
Found: C, 62.29; H, 5.66; N, 3.15.
1
(neat) 3427, 1727, 1614, 1305, and 1179 cm-1; H NMR (300 MHz,
CDCl3) δ 1.12 (t, 6H, J ) 7.2 Hz), 1.33 (m, 2H), 1.48 (m, 2H), 3.40
(q, 4H, J ) 7.1 Hz), and 9.65 (s, 1H); 13C NMR (75 MHz, CDCl3) δ
12.2, 13.6, 16.2, 21.9, 28.6, 38.3, 42.3, 168.1, and 174.9; HRMS calcd
for [C9H15NO3 + Li] 192.1211, found 192.1208.
3-(1-Diethylcarbamoylcyclopropyl)-3-oxopropionic Acid Ethyl
Ester. To a solution containing 2.4 g (18.1 mmol) of 2-carboethoxy-
acetic acid in 100 mL of THF at 0 °C was slowly added 18.1 mL (36
mmol) of isopropylmagnesium chloride, and the reaction mixture was
stirred at 0 °C for 30 min. In a separate flask, 2.6 mL (30 mmol) of
oxalyl chloride and 2 drops of DMF were slowly added to a solution
of 2.8 g (15 mmol) of 1-diethylcarbamoylcyclopropane carboxylic acid
in 100 mL of CH2Cl2. The solution was allowed to stir for 2 h at room
temperature and was then concentrated under reduced pressure. The
residue was taken up in 5 mL of THF, and the solution was added to
the above magnesium dianion solution. The resulting mixture was stirred
at 0 °C for 1 h and was quenched with 50 mL of a 50% HCl solution.
The mixture was extracted with ether and dried over MgSO4. Purifica-
tion of the crude residue by silica gel chromatography gave 2.5 g (65%)
of 3-(1-diethylcarbamoylcyclopropyl)-3-oxopropionic acid ethyl ester
as a yellow oil: IR (neat) 1746, 1699, 1640, 1327, 1248, and 1030
cm-1; 1H NMR (300 MHz, CDCl3) δ 1.12 (t, 6H, J ) 7.2 Hz), 1.22 (t,
3H, J ) 7.2 Hz), 1.34 (m, 2H), 1.47 (m, 2H), 3.37 (q, 4H, J ) 6.6
Hz), 3.51 (s, 2H), and 4.14 (q, 2H, J ) 7.2 Hz); 13C NMR (75 MHz,
CDCl3) δ 11.9, 13.1, 13.8, 16.7, 37.6, 39.3, 41.6, 45.6, 61.1, 166.4,
167.6, and 198.6. Anal. Calcd for C13H21NO4: C, 61.14; H, 8.29; N,
5.49. Found: C, 60.98; H, 8.15; N, 5.42.
6-Benzyl-5-methyl-4,7-dioxo-5-azaspiro[2.4]heptane-6-carboxyl-
ic Acid Ethyl Ester (22). To a solution containing 2 mg of rhodium(II)
acetate in 25 mL of refluxing benzene was added 0.5 g (1.5 mmol) of
diazo amide 20 dropwise over 20 min. The reaction mixture was heated
for 6 h, and the solvent was removed under reduced pressure. The crude
mixture was purified by silica gel chromatography to give 0.32 g (70%)
of 22 as a clear oil: IR (neat) 3028, 1761, 1734, 1706, 1597, 1502,
1
1380, 1237, and 1087 cm-1; H NMR (300 MHz, CDCl3) δ 0.86 (td,
1H, J ) 9.0 and 3.3 Hz), 1.01 (td, 1H, J ) 9.0 and 3.3 Hz), 1.26 (t,
3H, J ) 7.2 Hz), 1.53 (m, 2H), 3.04 (s, 3H), 3.24 (d, 1H, J ) 14.4
Hz), 3.54 (d, 1H, J ) 14.4 Hz), 4.26 (m, 2H), 6.97 (m, 2H), and 7.21
(m, 3H); 13C NMR (75 MHz, CDCl3) δ 13.4, 19.7, 21.0, 26.1, 30.3,
35.6, 62.0, 76.1, 126.8, 127.8, 129.3, 132.7, 166.0, 171.6, and 203.4.
Anal. Calcd for C17H19NO4: C, 67.74; H, 6.36; N, 4.65. Found: C,
67.62; H, 6.41; N, 4.51.
Spiro[4-(benzylmethylamino)-7-carboethoxy-7-hydroxy-1,3,6-tri-
oxo-2-phenyl-2,3,5,6,7,7a-hexahydro-1H-isoindole-5,1′-cyclopro-
pane] (23). To a solution containing 0.09 g (0.54 mmol) of N-phenyl-
maleimide and 2 mg of rhodium(II) acetate in 10 mL of refluxing
benzene was added 0.1 g (0.3 mmol) of diazo amide 20 dropwise over
20 min. The reaction mixture was heated for an additional 1 h, and the
solvent was removed under reduced pressure. The crude mixture was
2-Diazo-3-(1-diethylcarbamoylcyclopropyl)-3-oxopropionic Acid
Ethyl Ester (24). To a solution containing 2.5 g (9.8 mmol) of the
above ester in 50 mL of CH2Cl2 was added 2.7 mL (20 mmol) of
triethylamine, and the resultant mixture was stirred for 30 min at 0 °C.
At the end of this time, 1.5 mL (11.8 mmol) of mesyl azide was added
dropwise over a period of 15 min and the mixture was stirred for an
additional 24 h at room temperature. The mixture was quenched with
10% NaOH and extracted with CH2Cl2. Silica gel chromatography of

8166 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Padwa et al.
the crude mixture afforded 2.7 g (98%) of 24 as a labile yellow oil
a yellow oil that crystallized on standing, mp 46-50 °C: IR (neat)
2130, 1725, 1685, and 1640 cm-1; 1H NMR (200 MHz, CDCl3) δ 2.96
(s, 6H), 3.11 (s, 3H), and 3.74 (s, 3H); 13C NMR (50 MHz, CDCl3) δ
35.9, 39.5, 54.0, 72.2, 161.4, 163.7, and 165.6. Anal. Calcd for
C8H12N4O4: C, 42.11; H, 5.30; N, 24.55. Found: C, 41.91; H, 5.30;
N, 24.34.
1,1,3-Trimethyl-5-methoxycarbonyl-2-oxo-2,3-dihydro-1H-imid-
azol-1-ium-4-olate (29). A solution of 0.23 g (1 mmol) of diazo imide
28 in 5 mL of dry toluene was added dropwise over 1 h to a solution
of 2 mg of rhodium(II) acetate in 30 mL of toluene at reflux
temperature. After the resulting mixture was kept at reflux for an
additional 20 min, the solution was cooled in an ice bath. The
precipitated solid was filtered to give 0.14 g (68%) of 29 as a colorless
which was immediately used in the Rh(II)-catalyzed reaction: IR (neat)
1
2131, 1738, 1694, 1633, 1317, and 1127 cm-1; H NMR (300 MHz,
CDCl3) δ 0.94 (t, 6H, J ) 7.2 Hz), 1.15 (t, 3H, J ) 7.2 Hz), 1.26 (s,
4H), 3.24 (brs, 4H), and 4.13 (q, 2H, J ) 7.2 Hz); 13C NMR (75 MHz,
CDCl3) δ 12.2, 12.9, 13.1, 13.9, 14.0, 35.6, 39.9, 41.5, 61.4, 75.5, 160.1,
167.2, and 185.8.
5-Ethyl-4,7-dioxo-5-azaspiro[2,4]heptane-6-carboxylic Acid Ethyl
Ester (25). To a solution containing 2 mg of rhodium(II) acetate in 25
mL of refluxing benzene was added 0.5 g (1.8 mmol) of the diazo
amide 24 dropwise over 20 min. The mixture was heated for an
additional 5 h, and the solvent was removed under reduced pressure.
The crude residue was purified by silica gel chromatography to give
0.37 g (93%) of 25 as a clear oil: IR (neat) 1768, 1741, 1700, 1201,
1120, and 1019 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.16 (t, 3H, J )
7.2 Hz), 1.29 (t, 3H, J ) 7.2 Hz), 1.61 (m, 2H), 1.72 (m, 2H), 3.19
solid, mp 199-201 °C: IR (KBr) 1810, 1720, 1630, and 1440 cm-1
;
1H NMR (200 MHz, CDCl3) δ 3.15 (s, 3H), 3.46 (s, 6H), and 3.79 (s,
3H); 13C NMR (50 MHz, CDCl3) δ 25.2, 49.2, 50.2, 93.1, 155.4, 156.0,
and 161.0. Anal. Calcd for C8H12N2O4: C, 48.00; H, 6.04; N, 13.99.
Found: C, 48.15; H, 6.14; N, 13.89.
(m, 1H), 3.95 (m, 1H), 4.26 (q, 2H, J ) 7.2 Hz), and 4.64 (s, 1H); 13
C
NMR (75 MHz, CDCl3) δ 12.1, 13.8, 20.5, 21.8, 30.7, 36.3, 62.4, 67.7,
165.0, 171.5, and 200.2. Anal. Calcd for C11H15NO4: C, 58.66; H, 6.71;
N, 6.22. Found: C, 58.43; H, 6.69; N, 6.17.
The mother liquor of the above reaction was evaporated under
reduced pressure, and the residue was purified by silica gel chroma-
tography to give 0.02 g (10%) of the corresponding dimeric azine22 as
a yellow solid, mp 159-160 °C: IR (KBr) 1950, 1750, 1690, 1670,
and 1500 cm-1;1H NMR (200 MHz, CDCl3) δ 2.96 (s, 12H), 3.18 (s,
6H), and 3.88 (s, 6H);13C NMR (50 MHz, CDCl3) δ 32.4, 37.5, 53.1,
153.0, 157.3, 159.6, and 162.4; FAB-MS: 429 (M + 1). Anal. Calcd
for C16H24N6O8: C, 44.86; H, 5.65; N, 19.62. Found: C, 44.65; H,
5.63; N, 19.38.
Trimethyl 3-Dimethylamino-1-methyl-2,6-dioxo-1,2,3,6-tetrahy-
dro-3,4,5-pyridinetricarboxylate (30). A solution of 0.23 g (1 mmol)
of diazo imide 28 in 5 mL of dry toluene was added dropwise to a
solution of 2 mg of rhodium(II) acetate and 0.28 g (2 mmol) of dimethyl
acetylenedicarboxylate in 30 mL of toluene at reflux temperature. After
the resulting mixture was kept at reflux for an additional 20 min, the
solution was cooled in an ice bath. The precipitated solid was filtered
to give 0.06 g (28%) of ylide 31 as a colorless solid, identical in all
respects with a sample obtained above. Evaporation of the mother liquor
and purification of the residue by careful silica gel chromatography
provided 62 mg (18%) of trimethyl 3-dimethylamino-1-methyl-2,6-
dioxo-1,2,3,6-tetra-hydro-3,4,5-pyridinetricarboxylate (30) as a yellow
solid, mp 156-158 °C, and 0.07 g (25%) of trimethyl 5-dimethylamino-
2,3,4-furan tricarboxylate (33) as a colorless solid, mp 107-108 °C.
Compound 30 exhibited the following properties: IR (KBr) 1780, 1745,
1738, 1720, 1690, and 1660 cm-1; 1H NMR (200 MHz, CDCl3) δ 2.45
(s, 6H), 3.27 (s, 3H), 3.77 (s, 3H), 3.82 (s, 3H), and 3.89 (s, 3H); 13C
NMR (50 MHz, CDCl3) δ 26.6, 40.7, 53.3, 53.6, 53.7, 71.0, 131.5,
141.4, 160.6, 162.9, 163.0, 165.0, and 165.8. Anal. Calcd for
C14H18N2O8: C, 49.12; H, 5.30; N, 8.18. Found: C, 49.07; H, 5.36; N,
7.88.
Dimethyl 5-Carboethoxy-5,8-epoxy-8-(diethylcarbamoyl)-4-oxo-
6-spiro[2.5]-octene-6,7-dicarboxylate (26). To a solution containing
0.07 mL (0.53 mmol) of dimethyl acetylenedicarboxylate and 2 mg of
rhodium(II) acetate in 8 mL of refluxing benzene was added 0.1 g (0.36
mmol) of diazo amide 24 dropwise over a 20 min interval. The mixture
was heated for an additional 1 h, and the solvent was removed under
reduced pressure. The crude residue was purified by silica gel
chromatography to give 0.13 g (92%) of 26 as a yellow solid: mp
104-105 °C; IR (KBr) 1772, 1759, 1726, 1694, 1271, and 1082 cm-1
;
1H NMR (300 MHz, CDCl3) δ 1.07 (t, 6H, J ) 7.1 Hz), 1.24 (m, 1H),
1.30 (t, 3H, J ) 7.1 Hz), 1.35 (m, 1H), 1.67 (m, 2H), 3.34 (m, 4H),
3.65 (s, 3H), 3.78 (s, 3H), and 4.27 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 12.9, 13.6, 13.9, 16.2, 28.7, 45.8, 51.3, 52.5, 61.9, 101.4,
128.8, 137.8, 158.5, 161.7, 164.2, 166.9, and 168.2. Anal. Calcd for
C19H25NO8: C, 57.71; H, 6.37; N, 3.54. Found: C, 57.74; H, 6.36; N,
3.50.
Spiro[7-carboethoxy-4-(diethylamino)-7-hydroxy-1,3,6-trioxo-2-
phenyl-2,3,5,6,7,7a-hexahydro-1H-isoindole-5,1′-cyclopropane] (27).
To a solution containing 0.09 g (0.54 mmol) of N-phenylmaleimide
and 2 mg of rhodium(II) acetate in 8 mL refluxing benzene was added
0.1 g (0.36 mmol) of diazo amide 24 dropwise over 20 min. The mixture
was heated at 80 °C for 2 h, and the solvent was removed under reduced
pressure. The crude mixture was purified by silica gel chromatography
to give 0.1 g (66%) of 27 as a yellow solid: mp 180-181 °C; IR
1
(neat) 3453, 1752, 1706, 1693, 1594, 1371, and 1109 cm-1; H NMR
(300 MHz, CDCl3) δ 1.05 (t, 6H, J ) 7.2 Hz), 1.33 (t, 3H, J ) 7.2
Hz), 1.50 (m, 2H), 1.63 (m, 1H), 2.11 (m, 1H), 3.33 (m, 2H), 3.48 (m,
2H), 3.99 (s, 1H), 4.39 (m, 3H), 7.31 (m, 3H), and 7.42 (m, 2H); 13C
NMR (75 MHz, CDCl3) δ 13.7, 13.9, 14.0, 27.7, 30.7, 34.2, 46.5, 47.7,
63.4, 76.5, 102.5, 126.6, 128.0, 128.7, 132.2, 156.8, 164.0, 170.2, 171.2,
and 200.5. Anal. Calcd for C23H26N2O6: C, 64.78; H, 6.15; N, 6.57.
Found: C, 64.55; H, 5.97; N, 6.40.
Compound 33 exhibited the following properties: IR (KBr) 1750,
1
1700, 1610, and 1450 cm-1; H NMR (200 MHz, CDCl3) δ 3.20 (s,
6H), 3.73 (s, 3H), 3.82 (s, 3H), and 3.92 (s, 3H); 13C NMR (50 MHz,
CDCl3) δ 40.4, 51.5, 52.0, 52.8, 91.4, 129.5, 129.6, 157.7, 161.6, 161.8,
and 164.3. Anal. Calcd for C12H15NO7: C, 50.53; H, 5.30; N, 4.91.
Found: C, 50.36; H, 5.25; N, 4.77.
N′-(2-Diazo-2-methyloxycarbonylacetyl)-N,N,N′-trimethylurea (28).
A mixture of 2.0 g (20 mmol) of trimethylurea, 3.8 g (28 mmol) of
distilled methyl malonyl chloride, and 50 mL of dry benzene was heated
at reflux for 2 h. After all the starting material had been consumed,
the solution was cooled to ambient temperature. The solvent was
removed under reduced pressure, and the crude product was purified
by silica gel chromatography to give 3.9 g (96%) of N′-(2-methyloxy-
carbonylacetyl)-N,N,N′-trimethylurea as a colorless oil: IR (neat) 3550,
A mixture of 0.1 g (0.5 mmol) of ylide 29, 0.14 g (1 mmol) of
dimethyl acetylenedicarboxylate, and 2 mL of dry toluene was heated
at reflux for 2 h. After the solvent was removed under reduced pressure,
the crude residue was purified by silica gel chromatography to give
0.1 g (61%) of pyridine 30, identical in all respects with a sample
obtained above.
Methyl 4-Dimethylamino-7-hydroxy-2,5,7-trimethyl-1,3,6-trioxo-
2,3,5,-6,7,7a-hexahydro-1H-pyrrolo[3,4-c]pyridine-7-carboxylate
(35). A solution of 0.23 g (1 mmol) of diazo imide 28 in 5 mL of dry
toluene was added dropwise to a solution of 2 mg of rhodium(II) acetate
and 0.21 g (2 mmol) of N-methylmaleimide in 30 mL of toluene at
reflux temperature. After the resulting mixture was kept at reflux for
an additional 20 min, the solution was cooled in an ice bath. The
precipitated solid was filtered to give 0.09 g (46%) of ylide 29.
Evaporation of the mother liquor and purification of the residue by
silica gel chromatography provided 0.08 g (24%) of 35 as a pale yellow
solid, mp 178-180 °C: IR (KBr) 3400, 1750, 1690-1660, 1620, and
1
2950, 1745, and 1670 cm-1; H NMR (200 MHz, CDCl3) δ 2.97 (s,
3H), 3.05 (s, 3H), 3.58 (s, 2H), and 3.68 (s, 3H); 13C NMR (50 MHz,
CDCl3) δ 35.0, 39.3, 43.7, 54.2, 168.3, and 169.7.
A mixture of 2.0 g (10 mmol) of the above urea, 1.6 g (13 mmol)
of mesyl azide, 2.6 g (26 mmol) of distilled triethylamine, and 50 mL
of dry CH2Cl2 was stirred at room temperature for 48 h. After all starting
material had been consumed, the reaction mixture was washed with
ice-cold 5% aqueous KOH and brine. The organic layer was dried over
Na2SO4, and the solvent was removed under reduced pressure. The
crude diazo compound was purified by silica gel chromatography to
give 1.8 g (81%) of diazo imide 28 (78% based on trimethylurea) as

+
Rh(II)-Catalyzed Equilibration of CO and NH4 Ylides
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8167
1500 cm-1;1H NMR (200 MHz, CDCl3) δ 2.97 (s, 3H), 3.07 (s, 6H),
3.13 (s, 3H), 3.98 (s, 3H), and 4.02 (s, 1H);13C NMR (50 MHz, CDCl3)
δ 24.3, 32.7, 42.2, 46.1, 54.1, 75.3, 83.2, 152.5, 166.7, 168.1, 170.2,
and 171.7. Anal. Calcd for C13H17N3O6: C, 50.16; H, 5.50; N, 13.50.
Found: C, 50.44; H, 5.55; N, 13.45.
Reaction of Ammonium Ylide 29 with DMAD and Rhodium(II)
Acetate. A mixture of 0.1 g (0.5 mmol) of ylide 29, 0.14 g (1 mmol)
of DMAD, 0.04 g (0.2 mmol) of Rh(II) acetate and 2 mL of dry toluene
was heated at reflux for 30 min. After the solvent was removed under
reduced pressure, the crude residue was purified by flash chromatog-
raphy (ether/hexane 6:1) to yield 0.06 g (32%) of pyridine 30 and 0.02
g (10%) of furan 33 identical in all respects with the samples obtained
above.
Computational Considerations All quantum mechanical calcula-
tions described were performed with Gaussian-9452 and Gaussian-9853
on IBM RS6000 workstations at the Emerson Center, Department of
Chemistry, Emory University. In most cases, preliminary structures were
generated by force field calculations using MacroModel54 on local
Silicon Graphics Workstations or derived from X-ray structure data.55
Further preliminary structural manipulations were performed with
Molecule (V. 1.2.2) on the Macintosh.56 The latter platform was
subsequently used for cross-network job submission, structure data
retrieval, molecular viewing, and graphics generation (e.g., Figures 2,
3, and 5). Thus, all the structures in Scheme 1 were submitted to G-94
or G-98 for preliminary optimization: Becke3LYP/LANL2DZ/3-21G//
Becke3LYP/ LANL2DZ/3-21G. Hay and Wadt effective core potentials
(ECP2)57 and the LANL2DZ basis set were placed on Rh atoms, the
3-21G basis set on all other atoms. In the case of the Rh(II) complexes,
lack of convergence was initially a problem. With increasingly better
start geometries, the structures were ultimately induced to converge to
local minima. When optimization was achieved, a single point calcu-
lation along with NPA/NBO population analysis47 was performed:
Becke3LYP/LANL2DZ/6-31G*//Becke3LYP/LANL2DZ/3-21G. In a
few cases, diffuse functions were also employed in the 3-21+G and
6-31+G* basis sets. Bond orders quoted in the text are those from the
Wiberg formulation incorporated in the NPA population analysis.
Acknowledgment. A.P. gratefully acknowledges the Na-
tional Institute of Health (GM59384-21) and the National
Science Foundation (CHE-9806331) for generous support of
this work. C.O.K. wishes to acknowledge support from the
Austrian Academy of Sciences (O¨ AW, APART 319) and the
Austrian Science Fund (FWF, Project P-11994-CHE). J.P.S. is
grateful to Professor Dennis Liotta (Emory University) for partial
support of this work. C.O.K. wishes to thank Dr. Walter M. F.
Fabian (Graz) for DFT calculations on ylides 29 and 31.
(52) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.; Petersson, G.
A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrzewski,
V. G.; Ortiz, J. V.; Foresman, J. B.; Cioslowski, J.; Stefanov, B. B.;
Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen, W.;
Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Binkley, J. S.; Defrees, D. J.; Baker, J.; Stewart, J. P.; Head-
Gordon, M.; Gonzalez, C.; Pople, J. A. Gaussian 94, revision D.3; Gaussian,
Inc.: Pittsburgh, PA, 1995.
(53) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.;
Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A.
D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi,
M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.;
Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick,
D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.;
Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi,
I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M.
W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian 98, revision A.3; Gaussian,
Inc.: Pittsburgh, PA, 1998.
Supporting Information Available: 1H NMR spectra for
new compounds lacking elemental analyses together with
ORTEP drawings for structures 29 and 30 (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
JA001088J
(55) Cambridge Crystallographic Data Centre: http://csdvx2.ccdc.cam.ac.uk/
(56) van Eikema Hommes, N. J. R. Molecule for Macintosh, v 1.2.2,
Computer-Chemie-Centrum, Universita¨t Erlangen-Nu¨rnberg, Na¨gelsbach-
strasse 25, D-91052 Erlangen, Germany, 1994; hommes@organik.uni-
erlangen.de
(54) Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.;
Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J. Comput.
Chem. 1990, 11, 440; cf. http://www.schrodinger.com/macromodel2.html.
(57) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270; 284; 299.