High-diastereoselective and enantioselective cyclopropanation of α,β- unsaturated Fischer carbene complexes: Synthesis of chiral 1,2-disubstituted and 1,2,3-trisubstituted cyclopropanes

Article abstract of DOI:10.1021/jo9708708

Reaction of chiral vinylcarbene complexes 1 with in situ-generated iodomethyllithium or dibromomethyllithium gives cyclopropylcarbene complexes 4 and 13, respectively, with high diastereoselectivity (de > 91%). Different enantiopure 1,2-disubstituted and 1,2,3-trisubstituted cyclopropanes are obtained starting from chiral carbene complexes 4 and 13, respectively.

Full text of DOI:10.1021/jo9708708

6870
J . Org. Chem. 1997, 62, 6870-6875
High -Dia ster eoselective a n d En a n tioselective Cyclop r op a n a tion of
r,â-Un sa tu r a ted F isch er Ca r ben e Com p lexes: Syn th esis of Ch ir a l
1,2-Disu bstitu ted a n d 1,2,3-Tr isu bstitu ted Cyclop r op a n es
J ose´ Barluenga,* Pablo L. Bernad, J r., and J ose´ M. Concello´n*
Instituto Universitario de Quı´mica Organometa´lica “Enrique Moles”, Universidad de Oviedo,
J ulia´n Claverı´a 8, 33071-Oviedo, Spain
Alejandro Pin˜era-Nicola´s and Santiago Garc´ıa-Granda
Departamento de Quı´mica Fı´sica y Analı´tica, Facultad de Qu´ımica, J ulia´n Claver´ıa 8,
Universidad de Oviedo, 33071-Oviedo, Spain
Received May 15, 1997X
Reaction of chiral vinylcarbene complexes 1 with in situ-generated iodomethyllithium or dibro-
momethyllithium gives cyclopropylcarbene complexes 4 and 13, respectively, with high diastereo-
selectivity (de > 91%). Different enantiopure 1,2-disubstituted and 1,2,3-trisubstituted cyclopro-
panes are obtained starting from chiral carbene complexes 4 and 13, respectively.
In tr od u ction
the preparation of chiral cyclopropylcarbene complexes
is unprecedented.
Transition metal carbene complexes have become valu-
able reagents for organic synthesis.1 Among other in-
teresting properties, the synthetic usefulness of these
complexes is due to their rich reactivity, showing their
own unique types of reactivity. Specifically, cyclopropy-
lcarbene complexes can be transformed into cyclopen-
tenones,2 cyclopentadienones,3 cyclopentane-fused oxygen
heterocycles,4 cycloheptadienones,5 alkenyl halides,6 and
donor-acceptor-substituted cyclopropanes.7 Moreover,
cyclopropylcarbene complexes have been used in other
synthetic transformations under thermal8 or photochemi-
cal conditions.9 However, to the best of our knowledge,
On the other hand, based on the easy transformation
of carbene complexes into different organic compounds,10
the synthesis of chiral substituted cyclopropylcarbene
complexes could open new routes to a wide variety of
chiral substituted cyclopropanes. Chiral cyclopropanes
are highly useful intermediates in organic synthesis,11
and the cyclopropane ring is present in a great number
of natural products12 as well as in molecules used as
probes in biological processes.13 For this reason, signifi-
cant advances have been made in the synthesis of chiral
cyclopropanes.14 However, a total control of the stereo-
selectivities on the synthesis of 1,2-disubstituted cyclo-
propanes is still out of reach. Furthermore, reports on
an intermolecular enantioselective synthesis of 1,2,3-
trisubstituted cyclopropanes are scarce, mainly because
X Abstract published in Advance ACS Abstracts, September 15, 1997.
(1) For recent reviews of transition metal carbene complex chem-
istry, see: (a) Do¨tz, K. H. Angew. Chem., Int. Ed. Engl. 1984, 23, 587.
(b) Do¨tz, K. H.; Fischer, H.; Hofmann, P.; Kreissel, F. R.; Schubert,
U.; Weiss, K. Transition Metal Carbene Chemistry; Verlag Chemie:
Deerfield Beach, 1984. (c) Wulff, W. D. In Advances in Metal-Organic
Chemistry; Liebeskind, L. S., Ed.; J AI: Greenwich, 1989; Vol. 5, p 209.
(d) Wulff, W. D. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5, p 1065. (e) Wulff,
W. D. In Comprehensive Organic Synthesis II; Abel, A. W., Stone, F.
G. A., Wilkinson, G., Eds.; Pergamon: Oxford, 1995; Vol. 12, p 469. (f)
Hegedus, L. S. In Comprehensive Organometallic Chemistry II; Abel,
A. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, 1995;
Vol. 12, p 549.
(2) Cycloaddition with alkynes: (a) Herndon, J . W.; Tumer, S. U.;
Schnatter, W. F. K. J . Am. Chem. Soc. 1988, 110, 3334. (b) Herndon,
J . W.; Tumer, S. U. Tetrahedron Lett. 1989, 30, 295. (c) Herndon, J .
W.; Tumer, S. U.; McMullen, L. A.; Matasi, J . J .; Schnatter, W. F. K.;
Daitch, C. E. Comments Inorg. Chem. 1990, 10, 1. (d) Tumer, S. U.;
Herndon, J . W.; McMullen, J . A. J . Am. Chem. Soc. 1992, 114, 8394.
Intramolecular reaction from 2-alkenylcyclopropylcarbene com-
plexes: (e) Herndon, J . W.; McMullen, L. A. J . Am. Chem. Soc. 1989,
111, 6854. (f) Herndon, J . W.; Hill, D. K.; McMullen, L. A. Tetrahedron
Lett. 1995, 36, 5687. (g) Hill, D. K.; Herndon, J . W. Tetrahedron Lett.
1996, 37, 1359.
(3) Herndon, J . W.; Patel, P. P. Tetrahedron Lett. 1997, 38, 59.
(4) Herndon, J . W.; Matasi, J . J . J . Org. Chem. 1990, 55, 786.
(5) Starting from tungsten carbene complexes: (a) Herndon, J . W.;
Chatterjee, G.; Patel, P. P.; Matasi, J . J .; Tumer, S. U.; Harp, J . J .;
Reid, M. D. J . Am. Chem. Soc. 1991, 113, 7808. (b) Herndon, J . W.;
Zora, M.; Patel, P. P.; Chatterjee, G.; Matasi, J . J .; Tumer, S. U.
Tetrahedron 1993, 49, 5507. From molybdenum carbene complexes:
(c) Herndon, J . W.; Zora, M. Synlett 1993, 363.
(6) Herndon, J . W.; Reid, M. D. J . Am. Chem. Soc. 1994, 116, 383.
(7) Herndon, J . W.; Tumer, S. U. J . Org. Chem. 1991, 56, 286.
(8) (a) Herndon, J . W. Organometallics 1994, 13, 3370. (b) Zora,
M.; Herndon, J . W. J . Org. Chem. 1994, 59, 699. (c) Herndon, J . W.;
Hayford, A. Organometallics 1995, 14, 1556. (d) Herndon, J . W.; Patel,
P. P. J . Org. Chem. 1996, 61, 4500. (e) Krestschik, O.; Herndon, J .
W.; Patel, P. P. Organometallics 1996, 15, 3625.
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1988, 110, 2122. (b) Hegedus, L. S.; Bates, R. W.; So¨derberg, B. C. J .
Am. Chem. Soc. 1991, 113, 923. (c) Schwindt, M. A.; Miller, J . R.;
Hegedus, L. S. J . Organomet. Chem. 1991, 413, 143.
(10) Preparation of esters: (a) Casey, C. P.; Burkhardt, T. J .; Bunell,
C. A.; Calabrese, J . C. J . Am. Chem. Soc. 1977, 99, 2127. (b) Casey,
C. P.; Burkhardt, T. J . J . Am. Chem. Soc. 1972, 94, 6543. (c) Erker,
G.; Sosna, F. Organometallics 1990, 9, 1949. (d) Lluch, A.; J ordi, L.;
Sanchez-Baeza, F.; Ricart, S.; Camps, F.; Moreto´, J . M. Tetrahedron
Lett. 1992, 33, 3021. Synthesis of aldehydes: (e) Fischer, E. O.; Walz,
S.; Kreis, G.; Kreissl, F. R. Chem. Ber. 1977, 110, 1651. (f) Casey, C.
P.; Neumann, S. M. J . Am. Chem. Soc. 1977, 99, 1651. Synthesis of
methyl vinyl ethers: (g) Fischer, E. O.; Plabst, D. Chem. Ber. 1974,
107, 3326. Obtention of enol ethers: (h) Casey, C. P.; Bertz, S. H.;
Burkhardt, T. J . Tetrahedron Lett. 1973, 1421. (i) Casey, C. P.;
Burkhardt, T. J . J . Am. Chem. Soc. 1972, 94, 6543. Preparation of
methyl ketones: (j) Barluenga, J .; Bernad, P. L., J r.; Concello´n, J . M.
Tetrahedron Lett. 1994, 35, 9471.
(11) Reissig, H. U. Organic synthesis via cyclopropanes: principles
and applications. In The Chemistry of the Cyclopropyl Group; Patai,
S., Rappoport, Z., Eds.; J ohn Wiley and Sons: New York, 1987; Chapter
8.
(12) Liu, H. W.; Walsh, C. T. Biochemistry of the cyclopropyl group.
In The Chemistry of the Cyclopropyl Group; Patai, S., Rappoport, Z.,
Eds.; J ohn Wiley and Sons: New York, 1987; Chapter 16.
(13) Suckling, C. J . Angew. Chem., Int. Ed. Engl. 1988, 27, 537.
(14) For the use of chiral auxiliaries in asymmetric Simmons-Smith
reactions: (a) Charette, A. B.; Marcoux, J . F. Synlett 1995, 1997. (b)
Charette, A. B.; J uteau, H. J . Am. Chem. Soc. 1994, 116, 2651 and
references cited therein. For the asymmetric cyclopropanation by
diazoalkanes: (c) Doyle, M. P. Asymmetric cyclopropanation. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993;
Chapter 3. (d) Corey, E. J .; Grant, T. G. Tetrahedron Lett. 1994, 35,
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Int. Ed. Engl. 1992, 31, 430.
S0022-3263(97)00870-0 CCC: $14.00 © 1997 American Chemical Society

Synthesis of Chiral Substituted Cyclopropanes
J . Org. Chem., Vol. 62, No. 20, 1997 6871
Sch em e 1a
Ta ble 1. Syn th esis of Ch ir a l Cyclop r op ylca r ben e
Com p lexes 4
1
2
entry
M
R
X
product
yield (%)a
de (%)b
1
2
3
4
5
Cr
Cr
Cr
Cr
W
2-furyl
2-furyl
Ph
Ph
p-ClPh
Cl
I
Cl
I
4a
4a
4b
4b
4c
96
93
93
90
95
74
90
77
>95
>95
I
a
b
Isolated yield based on the starting vinylcarbene 1. Diaste-
reoisomeric excess determined by 300 MHz 1H NMR analysis of
the crude products 4.
Sch em e 2a
a
Reagents and conditions: (i) MeLi, THF/diethyl ether, 5 min
and then room temperature.
these compounds are generally obtained as diastereoi-
someric mixtures with poor enantiomeric excess.15
Recently, we have described a methodology for the
diastereoselective synthesis of trans-substituted chro-
mium cyclopropylmethoxycarbene complexes using chlo-
romethyllithium.16 In this paper we describe the syn-
thesis of chiral chromium cyclopropylalkoxycarbene
complexes 4 and 13. These compounds are obtained by
cyclopropanation of enantiomerically pure chromium
alkenyl[((-)-8-phenylmenthyl)oxy]carbene complexes 1
with in situ-generated monohalo- or dibromomethyl-
lithium. These processes take place with high-asym-
metric induction. Removal of the metal fragment and
the chiral auxiliary group leads to enantiopure 1,2-
disubstituted or 1,2,3-trisubstituted cyclopropanes, re-
spectively.
a
Reagents and conditions: (i) CH2N2, diethyl ether, 25 °C, 14
h; (ii) HCl (1 N), 25 °C, 24 h; (iii) CH2Br2, THF, then LDA (THF),
-78 °C, 5 min and then room temperature; (iv) pyridine N-oxide,
THF, 25 °C, 14 h; (v) LiAlH4, diethyl ether, 35 °C, 14 h; (vi) H2O,
25 °C; (vii) PhCOCl, Et3N, DMAP, CH2Cl2, 25 °C, 14 h.
Results in Table 1 show that (a) yields of carbene
complexes 4 were only moderately affected by the metal
in the starting carbene complexes 1; (b) the reactions of
carbene complexes 1 with chloromethyllithium or iodom-
ethyllithium gave essentially the same yields; (c) higher
diastereoselectivity (300 MHz, 1H NMR spectroscopy) was
obtained using iodomethyllithium (entries 2 and 4)
instead of chloromethyllithium (entries 1 and 3), which
can be explained because iodine is bulkier than chlorine.
To prove the usefulness of this methodology in the
synthesis of chiral 1,2-disubstituted cyclopropanes, we
have transformed the cyclopropylcarbene complexes 4
into different organic compounds. Thus, treatment of
cyclopropylcarbenes 4 with diazomethane10h afforded
chiral methyl ketones 5; reaction of 4b with dibromom-
ethyllithium18 gave chiral bromomethyl ketone 6b; treat-
ment of carbene complexes 4 with pyridine N-oxide10c
afforded cyclopropanecarboxylates 7, and further reduc-
tion of 7a (R ) 2-furyl) with LiAlH4 gave the correspond-
ing alcohol 8a (Scheme 2 and Table 2). Chiral auxiliary
was recovered in the synthesis of 5, 6, and 8a .
Resu lts a n d Discu ssion
Syn th esis of Ch ir a l 1,2-Disu bstitu ted Cyclop r o-
p ylca r ben e Com p lexes a n d Th eir Syn th etic Ap -
p lica tion s. Treatment of chiral vinylcarbene complexes
1 with chloromethyllithium or iodomethyllithium in situ
generated at -78 °C gave the corresponding cyclopropy-
lcarbene complexes 4, with high diastereoselectivity (see
the Experimental Section, Scheme 1, and Table 1).
Compounds 1 were obtained by alkylation of tetram-
ethylammonium-derived methylcarbene complex with
(-)-8-phenylmenthol and further condensation.17 Chlo-
romethyllithium or iodomethyllithium were in situ gen-
erated by treatment of chloroiodomethane or diiodo-
methane, respectively, with methyllithium. As depicted
in Scheme 1, the 1,4-addition of halomethyllithium to
vinylcarbene complex 1 would lead to anionic intermedi-
ate 3; spontaneous γ-elimination of 3 yields the cyclo-
propylcarbene complex 4.
Except in the oxidation reaction shown at entry 4
(Table 2), all reactions were carried out starting from the
cyclopropylcarbene complexes obtained using iodometh-
yllithium. All transformations proceeded with no detect-
able epimerization: compounds 5, 6b, 7, and 8a were
obtained with high diastereoselectivity, in agreement
(15) Synthesis of 1,2,3-trisubstituted cyclopropanes: (a) Ito, K.;
Katsuki, T. Synlett 1993, 638. (b) Lowenthal, R. E.; Abiko, A.;
Masamune, S. Tetrahedron Lett. 1990, 31, 6005. (c) Lowenthal, R. E.;
Masamune, S. Tetrahedron Lett. 1991, 32, 7373. (d) Kunz, T.; Reissig,
H. U. Tetrahedron Lett. 1989, 30, 2079. (e) Dammast, F.; Reissig, H.
U. Chem. Ber. 1993, 126, 2449. (f) Dammast, F.; Reissig, H. U. Chem.
Ber. 1993, 126, 2727.
(16) Barluenga, J .; Bernad, P. L., J r.; Concello´n, J . M. Tetrahedron
Lett. 1995, 36, 3937.
(17) Barluenga, J .; Montserrat, J . M.; Flo´rez, J .; Garc´ıa-Granda, S.;
Mart´ın, E. Angew. Chem., Int. Ed. Engl. 1994, 33, 1392.
(18) Unpublished results. Different Fischer carbene complexes can
be transformed into bromomethyl ketones by treatment with dibro-
momethyllithium.

6872 J . Org. Chem., Vol. 62, No. 20, 1997
Barluenga et al.
Ta ble 2. Syn th esis of Ch ir a l 1,2-Disu bstitu ted
Cyclop r op a n es
entry
starting compd
product
yield (%)a
de (%)b
1
2
3
4
5
6
7
8
4b
4c
4b
4a
4a e
4b
7a
8a
5b
5c
6b
7a
7a
7b
8a
9a
75c
80
>98
>98
>98
76
91
f
71d
76
78
76
76
>98
>98
95g
a
Isolated yield based on the starting compounds 4, 7, and 8a .
Diastereoisomeric excess determined by 300 MHz 1H NMR
b
analysis of the crude products 5-7, 8a , and 9a . c ee ) 99%, HPLC
(Chiracel OD-H; UV detector at 220 nm, 0.8 mL/min; hexane:2-
d
propanol, 100:1; tR 13.9 min). ee ) 97%, HPLC (Chiracel OD-H;
F igu r e 1. Molecular structure of 16 determined by X-ray
crystallography.
UV detector at 206 nm, 0.8 mL/min; hexane:2-propanol, 100:1; tR
29.0 min). e Compound 4a was obtained using chloromethyl-
lithium. f No de was available from the 1H NMR analysis of the
crude products. ee ) 91%, HPLC (Chiracel OD-H; UV detector
at 230 nm, 0.8 mL/min; hexane:2-propanol, 600:1; tR 32.5 min).
Ch a r t 1
g
with diastereoisomeric excess (de) of starting compounds
4 and 7a , respectively.
The enantiomeric purity of chiral 1,2-disubstituted
cyclopropanes was determined by chiral HPLC (Chiracel
OD-H) analysis. The enantiomeric excess (ee) values of
5b and 6b turned out to be 99% and 97%, respectively.
Alcohol 8a could not be resolved using the chiral column
Chiracel OD-H; in this case HPLC analysis was carried
out with the benzoic ester derivative 9a , prepared by
reaction of 8a with benzoyl chloride (ee ) 91%). All ee
determinations were in agreement with the de of the
starting cyclopropylcarbene complexes 4. To realize all
the HPLC analyses, racemic mixtures of 5b, 6b, and 9a
were prepared to exclude the probability of comigration
of both enantiomers in HPLC. Racemic mixtures of 5b,
6b, and 9a were obtained using the same methodology
starting from racemic vinylcarbene complexes.16
reoselectivity of enolates of Fischer vinylcarbene com-
plexes.
Syn th esis of Ch ir a l 1,2,3-Tr isu bstitu ted Cyclo-
p r op ylca r ben e Com p lexes a n d Th eir Syn th etic Ap -
p lica tion s. Previously to the preparation of enantiopure
1,2,3-trisubstituted cyclopropanes, the diastereoselectiv-
ity of this cyclopropanation reaction of achiral R,â-
unsaturated carbene complexes was studied. So, when
vinylcarbene complexes 10 reacted with dibromometh-
yllithium in situ generated at -78 °C, 1,2,3-trisubstituted
cyclopropylcarbene complexes 13a ,b were obtained
(Scheme 3 and Table 3). Dibromomethyllithium was in
situ generated by treatment of dibromomethane with
lithium diisopropylamide (LDA). No important differ-
ences were observed in the synthesis of 13a or 13b
starting from chromium or tungsten carbene complex.
The proposed mechanism involves the 1,4-addition of
dibromomethyllithium to carbene complex 10 and further
spontaneous γ-elimination of intermediate 12.
The relative trans-configuration in the cylclopropane
ring of compounds 4-7, 8a , and 9a was established by
1H NMR coupling constant analysis.19 The absolute
configuration of these 1,2-disubstituted cyclopropane
rings, as depicted in Schemes 1 and 2, was assigned by
analogy with the X-ray analysis showed in Figure 1.20
The asymmetric induction observed in the cyclopropa-
nation reaction can be explained assuming that in the
most stable conformation of 1, the chiral auxiliary phenyl
group shields selectively the double bond (Re,Re)-face by
π,π-orbital overlap,21 forcing the nucleophile to approach
preferentially from the (Si,Si)-face (Chart 1). This model
is similar to the “π-stacking” one proposed by Oppolzer22
for cuprate additions to enolates and the one depicted
by Nakamura23 to explain the Michael addition diaste-
1,2,3-Trisubstituted cyclopropylcarbene complex 13a
was transformed into the corresponding ester 14,10c
methyl ketone 15,10h and bromomethyl ketone 1618 as
racemic mixtures using the same methodologies de-
scribed above. The synthesis of all compounds took place
(19) Morris, D. G. Nuclear magnetic resonance and infrared spectra
of cyclopropanes and cyclopropenes. In The Chemistry of the Cyclo-
propyl Group; Patai, S., Rappoport, Z., Eds.; J ohn Wiley and Sons: New
York, 1987; Chapter 3.
(20) The authors have deposited atomic coordinates for this struc-
ture with the Cambridge Crystallographic Data Centre. The coordi-
nates can be obtained, on request, from the Director, Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
U.K.
(21) Evidence for π,π-attractive interactions: (a) Corey, E. J .;
Matsumura, Y. Tetrahedron Lett. 1991, 32, 6289. (b) Corey, E. J .; Loh,
T. P. J . Am. Chem. Soc. 1991, 113, 8966. (c) Hawkins, J . M.; Loren,
S. J . Am. Chem. Soc. 1991, 113, 7794 and references cited therein.
(22) (a) Oppolzer, W.; Lo¨her, H. J . Helv. Chim. Acta 1981, 64, 2808.
(b) d’Angelo, J .; Maddaluno, J . J . Am. Chem. Soc. 1986, 108, 8112.
(23) Nakamura, E.; Tanaka, K.; Fujimura, T.; Aoki, S.; Williard, P.
G. J . Am. Chem. Soc. 1993, 115, 9015.
1
with total diastereoselectivity; thus, 300 H MHz NMR
analysis of reaction crudes shows the presence of one
diastereoisomer exclusively. The relative configuration
of substituents in the cyclopropane ring, shown in
Scheme 3, was assigned on the basis of the value of
coupling constants between the cyclopropane protons.20
So, for example, in racemic 15, the value of J CHBr-CHPh
)
8.1 Hz is in agreement with the cis-relationship of the
bromine and phenyl substituents; the value of J O)C-CH-CHBr
) 3.8 Hz is according to the trans-relationship of the
bromine and acetyl substituents.

Synthesis of Chiral Substituted Cyclopropanes
J . Org. Chem., Vol. 62, No. 20, 1997 6873
Sch em e 3a
mixtures of 15 and 16 were used as standard reference.
The absolute configuration of 16, as depicted in Scheme
3, was established by X-ray analysis (Figure 1).20 By
analogy to this one, the configuration of the rest of the
compounds was assigned.
In conclusion, this paper describes a convenient and
versatile methodology for the preparation of different
enantiopure 1,2-disubstituted and 1,2,3-trisubstituted
cyclopropanes with high yield through a simple and rapid
cyclopropanation of enantiomerically pure chromium
alkenyl[((-)-8-phenylmenthyl)oxy]carbene complexes with
in situ-generated monohalo- or dibromomethyllithium.
Exp er im en ta l Section
Gen er a l. All reactions were conducted under an atmo-
sphere of dry nitrogen using oven-dried glassware and sy-
ringes. Temperatures are reported as bath temperatures.
Solvents were dried according to established protocols by
distillation under nitrogen from appropiate drying agent.
Thus, THF and Et2O were distilled from sodium/benzophenone
ketyl and CH2Cl2 from P2O5. Solvents used in extraction and
purification were distilled prior to use.
Analytical TLC was performed on glass-backed plates coated
with silica gel (60 Å) with F254 indicator; compounds were
visualized with UV light or iodine. Melting points were
obtained with open capillary tubes and are uncorrected. 1H
NMR spectra were recorded at 200 or 300 MHz with TMS (δ
) 0.0) as internal reference. 13C NMR spectra were recorded
at 50 or 75 MHz with CDCl3 (δ ) 76.95) as internal reference.
Only the most significant IR absortions and the molecular ions
and/or base peaks in MS are given. The enantiomeric purity
was determined by chiral HPLC analysis using a Chiracel
OD-H column (25 × 0.46 cm).
a
Reagents and conditions: (i) LDA (diethyl ether), THF/diethyl
ether, -78 °C, 5 min and then room temperature; (ii) pyridine
N-oxide, THF, 25 °C, 14 h; (iii) CH2N2, diethyl ether, 25 °C, 14 h;
(iv) HCl (1 N), 25 °C, 24 h; (v) CH2Br2, THF, then LDA (THF),
-78 °C, 5 min and then room temperature.
Ta ble 3. Syn th esis of 1,2,3-Tr isu bstitu ted
Cyclop r op ylca r ben e Com p lexes: Obten tion of
1,2,3-Tr isu bstitu ted Cyclop r op a n es
Reagents were purchased from commercial sources and used
without further purification unless otherwise indicated. Py-
ridine N-oxide was freshly sublimated prior to use. The
diazomethane solution in diethyl ether was immediately
prepared prior to use from N-nitrosomethylurea.24 Silica gel
(60 Å) for flash chromatography was purchased from com-
mercial sources (200-450 mesh). Starting vinylcarbene com-
plexes 1 and 13 were prepared according to a published
procedure.25
Gen er a l P r oced u r e for th e P r ep a r a tion of 1,2-Disu b-
stitu ted Cyclop r op ylca r ben e Com p lexes 4. To a -78 °C
stirred solution of the corresponding chiral vinylcarbene
complex 1 (1 mmol) and chloroiodomethane (0.15 mL, 2 mmol)
or diiodomethane (0.16 mL, 2 mmol) in THF (5 mL) and Et2O
(15 mL) was added methyllithium (1.3 mL of 1.5 M solution
in Et2O, 2 mmol) dropwise over 5 min. After stirring at -78
°C for 5 min, the mixture was allowed to warm to room
temperature and the reaction quenched with silica gel (ca. 2
g). The solvents were distilled (0.1 mmHg), and the residue
was subjected to flash column chromatography over silica gel
(hexane:AcOEt, 40:1) to provide cyclopropylcarbene complexes
4.
P e n t a c a r b o n y l{[(1S ,2S )-2-(2-fu r y l)c y c lo p r o p y l]-
[((1R ,3R ,4S )-8-p h e n y lm e n t h y l)o x y ]m e t h y li d e n e }-
ch r om iu m (0) (4a ): yellow oil; Rf 0.48 (Hex:AcOEt, 20:1); 1H
NMR δ 0.8-1.4 (m, 13 H), 1.6-1.7 (m, 4 H), 1.9-2.0 (m, 1 H),
2.4-2.5 (m, 2 H), 3.6 (ddd, J ) 4.0, 5.2, 8.2 Hz, 1 H), 5.3 (td,
J ) 4.0, 10.5 Hz, 1 H), 6.0 (d, J ) 3.2 Hz, 1 H), 6.3 (dd, J )
1.9, 3.1 Hz, 1 H), 7.0-7.3 (m, 6 H); 13C NMR δ 21.6, 24.7, 25.4,
23.5, 25.4, 28.8, 31.0, 34.2, 40.3, 50.3, 51.5, 92.5, 105.5, 110.3,
125.3, 125.7, 128.3, 141.2, 150.6, 152.9, 216.5, 223.3, 346.3;
IR (neat) 2062, 1917 cm-1; MS m/z 542 (M+, 2), 458 (7), 262
(10), 170 (15), 164 (16), 136 (24), 120 (15), 119 (100), 118 (15),
entry
starting compd
product
yield (%)a
de (%)b
1
2
3
4
5
6
7
8
10a
10b
1b
13a
13a
13a
13c
13c
13a
13b
13c
77
74
87
87
83
85
83c
76c
>95
>95
>95
>98
>98
>98
>98
>98
(()-14
(()-15
(()-16
(+)-15
(+)-16
a
Isolated yield based on the starting compounds 1, 10, and 13.
Diastereoisomeric excess determined by 300 MHz 1H NMR
b
analysis of the crude products 13-16. c ee > 95%, HPLC [Chiracel
OD-H; UV detector at (15) 220 nm, 0.8 mL/min; (15) hexane:2-
propanol, 75:1, (16) hexane:2-propanol, 10:1; tR (15) 13.3 min, (16)
13.7 min].
The synthesis of enantiopure chromium cyclopropyl-
carbene complex 13c was achieved starting from the
corresponding carbene complex 1b; its reaction with in
situ-generated dibromomethyllithium furnished the chiral
1,2,3-trisubstituted cyclopropylcarbene complex 13c with
1
very high diastereoselectivity (300 MHz H NMR spec-
troscopy).
Cleavage of the pentacarbonyl moiety and recovery of
chiral auxiliary were performed using diazomethane10h
or dibromomethyllithium,18 giving rise to the correspond-
ing chiral methyl ketone 15 or bromomethyl ketone 16,
respectively (Table 3 and Scheme 3). The synthesis of
15 and 16 took place without detectable epimerization
(300 MHz 1H NMR spectroscopy). The enantiomeric
purity of 15 and 16 was determined by chiral HPLC
analysis, showing that the synthesis of 13c, 15, and 16,
in which three stereogenic centers are generated, pro-
ceeds with high enantiomeric excess (ee > 95%). To
perform the HPLC analysis, the corresponding racemic
(24) Arndt, F. In Organic Syntheses; Blatt, A. H., Ed.; J ohn Wiley
and Sons: New York, 1948; Collect. Vol. 2, p 165.
(25) (a) Barluenga, J .; Montserrat, J . M.; Flo´rez, J .; Garc´ıa-Granda,
S.; Mart´ın, E. Chem. Eur. J . 1995, 1, 236. (b) Aumann, R.; Heinen,
H. Chem. Ber. 1987, 120, 537.

6874 J . Org. Chem., Vol. 62, No. 20, 1997
Barluenga et al.
105 (79), 91 (70), 79 (18), 77 (20), 55 (12), 52 (17). Anal. Calcd
for C29H30O7Cr: C, 64.24; H, 5.57. Found: C, 64.24; H, 5.50.
P e n t a c a r b o n y l{[(1 S ,2 S )-2 -p h e n y l c y c l o p r o p y l ]-
[((1R ,3R ,4S )-8-p h e n y lm e n t h y l)o x y ]m e t h y li d e n e }-
ch r om iu m (0) (4b): yellow oil; Rf 0.54 (Hex:AcOEt, 21:1); 1H
NMR δ 0.8-1.8 (m, 17 H), 2.0-2.1 (m, 1 H), 2.4-2.5 (m, 1 H),
2.8-2.9 (m, 1 H), 3.65 (ddd, J ) 3.9, 5.1, 8.1 Hz, 1 H), 5.4 (td,
J ) 4.1, 10.5 Hz, 1 H), 7.0-7.5 (m, 10 H); 13C NMR δ 21.6,
24.0, 25.5, 27.0, 30.3, 31.0, 32.1, 34.2, 40.6, 41.1, 51.6, 53.0,
94.2, 125.4, 125.7, 126.7, 126.8, 128.3, 128.4, 139.3, 151.0,
216.7, 223.3, 346.4; IR (neat) 2058, 1929 cm-1; MS m/z 552
(M+, <1), 146 (12), 120 (13), 119 (100), 118 (20), 117 (12), 115
(11), 105 (50), 91 (40), 52 (11). Anal. Calcd for C31H32O6Cr:
C, 67.38; H, 5.84. Found: C, 67.02; H, 5.77.
P e n t a c a r b o n y l{[(1S ,2S )-2-(p -c h lo r o p h e n y l)c y c lo -
p r o p y l ] [ ( ( 1 R , 3 R , 4 S ) - 8 - p h e n y l m e n t h y l ) o x y ] -
m eth ylid en e}tu n gsten (0) (4c): yellow oil; Rf 0.60 (Hex:
AcOEt, 20:1); 1H NMR δ 0.8-1.8 (m, 17 H), 2.0-2.1 (m, 1 H),
2.4-2.5 (m, 1 H), 2.8-2.9 (m, 1 H), 3.6-3.7 (m, 1 H), 5.4 (td,
J ) 4.1, 10.5 Hz, 1 H), 7.0-7.5 (m, 9 H); 13C NMR δ 22.6, 26.1,
26.7, 27.9, 30.0, 32.1, 32.2, 35.1, 41.2, 44.8, 52.2, 56.7, 95.7,
126.3, 126.7, 129.2, 129.5, 133.4, 138.9, 151.5, 198.7, 203.8,
322.1; IR (neat) 2066, 1931 cm-1; HRMS calcd for C31H31ClO6W
718.131 319, found 718.132 082; MS m/z 718 (M+, 25), 644 (18),
505 (98), 503 (100), 475 (47), 421 (79), 419 (86), 119 (85), 105
(59), 91 (27). Anal. Calcd for C31H31ClO6W: C, 51.79; H, 4.35.
Found: C, 51.67; H, 4.29.
126.8, 128.5, 139.4, 200.1; IR (neat) 1697 cm-1; HRMS calcd
for C11H11BrO 237.999 338, found 237.999 449; MS m/z 240
(M+ + 2, 4), 238 (M+, 4), 159 (48), 145 (18), 117 (100), 115
(62), 91 (31). Anal. Calcd for C11H11BrO: C, 55.25; H, 4.64.
Found: C, 55.17; H, 4.58.
Gen er a l P r oced u r e for th e P r ep a r a tion of Cyclop r o-
p a n eca r boxyla tes 7. To a 25 °C stirred solution of chiral
cyclopropylcarbene complex 4 (0.9 mmol) in THF (15 mL) was
added pyridine N-oxide (0.29 g, 3 mmol). After stirring at 25
°C for 14 h, the mixture was hydrolyzed with HCl (1 N) and
extracted with Et2O (3 × 10 mL). The combined organic layer
was dried (Na2SO4), filtered through Celite, and concentrated
in vacuo to give pure esters 7.
(1R,3R,4S)-8-P h en ylm en th yl (1S,2S)-2-(2-fu r yl)cyclo-
p r op a n eca r boxyla te (7a ): colorless oil; Rf 0.43 (Hex:AcOEt,
20:1); [R]293D ) +122.6 (c 0.61, CHCl3); 1H NMR δ 0.8-1.5 (m,
16 H), 1.6-1.7 (m, 2 H), 1.8-1.9 (m, 1 H), 2.0-2.1 (m, 1 H),
2.2-2.3 (m, 1 H), 4.8 (td, J ) 4.4, 10.8 Hz, 1 H), 6.0 (d, J ) 3.2
Hz, 1 H), 6.2 (dd, J ) 1.9, 3.2 Hz, 1 H), 7.1-7.3 (m, 6 H); 13C
NMR δ 14.8, 19.0, 21.7, 21.9, 25.0, 26.4, 27.6, 31.1, 34.4, 39.5,
41.6, 50.4, 74.6, 104.9, 110.2, 140.7, 124.9, 125.2, 127.8, 151.3,
153.3, 172.0; IR (neat) 1717 cm-1; MS m/z 366 (M+, <1), 214
(13), 152 (41), 135 (13), 119 (100), 107 (32), 105 (63), 91 (95),
81 (16), 79 (51), 78 (20), 77 (60), 55 (19), 53 (14), 41 (23). Anal.
Calcd for C24H30O3: C, 78.65; H, 8.25. Found: C, 78.41; H,
8.19.
(1R,3R,4S)-8-P h en ylm en t h yl (1S,2S)-2-p h en ylcyclo-
Gen er a l P r oced u r e for th e P r ep a r a tion of Cyclop r o-
p yl Meth yl Keton es 5. Diazomethane (10 mL of a solution
in Et2O, 3 mmol) was added to chiral cyclopropylcarbene
complexes 4 (0.9 mmol) at 25 °C, and the mixture was stirred
for 14 h. Then, the reaction mixture was hydrolyzed with HCl
(1 N) and extracted with Et2O (3 × 10 mL). The combined
organic layer was dried (Na2SO4), filtered, and concentrated
in vacuo. The crude product mixture was chromatographed
on silica gel (hexane:THF, 25:1, for 5b and hexane:AcOEt, 15:
1, for 5c) to recover chiral auxiliary and provide pure ketones
5.
p r op a n eca r boxyla te (7b): colorless oil; Rf 0.47 (Hex:AcOEt,
1
20:1); [R]293 ) +81.6 (c 0.67, CHCl3); H NMR δ 0.8-2.2 (m,
D
21 H), 4.7 (td, J ) 4.3, 10.7 Hz, 1 H), 6.9-7.2 (m, 10 H); 13C
NMR δ 17.3, 21.6, 24.1, 25.2, 25.8, 26.5, 27.6, 31.1, 34.4, 39.6,
41.7, 50.5, 74.6, 124.8, 125.3, 125.9, 126.2, 127.8, 128.2, 140.2,
151.5, 172.6; IR (neat) 1715 cm-1; HRMS calcd for C26H32O2
376.240 230, found 376.240 854; MS m/z 376 (M+, 14), 266 (16),
257 (23), 243 (20), 162 (21), 119 (100), 118 (22), 91 (21), 45
(14).
(1S,2S)-[2-(2-F u r yl)cyclop r op yl]m eth a n ol (8a ). To a 0
°C stirred solution of LiAlH4 (0.11 g, 3 mmol) in Et2O (10 mL)
was added a solution of ester 7a (0.37 g, 1 mmol) in Et2O (10
mL) dropwise over 15 min. The mixture was refluxed (35 °C)
for 14 h. After cooling to 0 °C, H2O (20 mL) was added. The
mixture was extracted with Et2O (3 × 10 mL). The solvents
were distilled (0.1 mmHg), and the crude product mixture was
subjected to flash column chromatography over silica gel
(hexane:AcOEt, 20:1) to recover chiral auxiliary and provide
Meth yl (1S,2S)-2-p h en ylcyclop r op yl k eton e (5b): color-
less oil; Rf 0.25 (Hex:AcOEt, 10:1); [R]293 ) +116.2 (c 0.785,
D
CHCl3); 1H NMR δ 1.4 (ddd, J ) 4.2, 6.6, 8.1 Hz, 1 H), 1.7
(ddd, J ) 4.2, 5.1, 9.1 Hz, 1 H) 2.25 (ddd, J ) 4.0, 5.1, 8.1 Hz,
1 H), 2.3 (s, 3 H), 2.55 (ddd, J ) 4.0, 6.6, 9.1 Hz, 1 H), 7.1-7.3
(m, 5 H); 13C NMR δ 18.9, 28.8, 30.6, 32.6, 125.7, 126.2, 128.2,
140.0, 206.7; IR (neat) 1696 cm-1; HRMS calcd for C11H12
O
160.088 815, found 160.087 967; MS m/z) 160 (M+, 25), 117
(100), 115 (43), 91 (28), 43 (35).
pure alcohol 8a as a colorless oil: Rf 0.12 (Hex:AcOEt, 5:1);
1
[R]293 ) +260 (c 0.735, CHCl3); H NMR δ 0.8-1.0 (m, 2 H),
D
(1S,2S)-2-(p-Ch lor op h en yl)cyclop r op yl m eth yl k eton e
1.4-1.5 (m, 1 H), 1.75-1.85 (m, 1 H), 3.3 (s br, 1 H), 3.55 (dd,
J ) 4.5, 6.7 Hz, 2 H), 5.95 (d, J ) 3.0 Hz, 1 H), 6.25 (dd, J )
1.7, 3.0 Hz, 1 H), 7.2 (d, J ) 1.7 Hz, 1 H); 13C NMR δ 11.1,
14.3, 22.5, 65.4, 103.5, 110.1, 140.3, 155.8; IR (neat) 3333, 1024
cm-1; HRMS calcd for C8H10O2 138.068 080, found 138.068 180;
MS m/z 138 (M+, 60), 107 (100), 95 (25), 94 (49), 77 (36).
(5c): colorless oil; Rf 0.44 (Hex:AcOEt, 3:1); [R]293D ) +370.75
1
(c 0.735, CHCl3); H NMR δ 1.3 (ddd, J ) 4.3, 6.6, 8.2 Hz, 1
H), 1.65 (ddd, J ) 4.3, 5.2, 9.1 Hz, 1 H), 2.15 (ddd, J ) 4.0,
5.2, 8.2 Hz, 1 H), 2.3 (s, 3 H), 3.45 (ddd, J ) 4.0, 6.6, 9.1 Hz,
1 H), 7.0 (d, J ) 8.4 Hz, 2 H), 7.2 (d, J ) 8.4 Hz, 2 H); 13C
NMR δ 18.8, 27.9, 30.5, 32.4, 127.1, 128.2, 131.8, 138.6, 206.1;
IR (neat) 1697 cm-1; HRMS calcd for C11H11ClO 194.049 843,
found 194.049 561; MS m/z 196 (M+ + 2, 20), 194 (M+, 60),
153 (30), 151 (91), 125 (19), 116 (57), 115 (82), 43 (100).
Gen er a l P r oced u r e for th e P r ep a r a tion of Br om om -
eth yl Cyclop r op yl Keton es 6. To a -78 °C stirred solution
of chiral cyclopropylcarbene complex 4 (0.9 mmol) and dibro-
momethane (0.11 mL, 1.5 mmol) in THF (5 mL) was added
LDA [prepared from MeLi (1 mL of 1.5 M solution in Et2O,
1.5 mmol) and diisopropylamine (0.21 mL, 1.5 mmol) in THF
(5 mL)] dropwise over 5 min. After stirring at -78 °C for 5
min, the mixture was allowed to warm to room temperature,
hydrolyzed with HCl (1 N) and extracted with Et2O (3 × 10
mL). The solvents were distilled (0.1 mmHg), and the crude
product mixture was subjected to flash column chromatogra-
phy over silica gel (hexane:Et2O, 30:1, for 6b) to recover chiral
auxiliary and provide pure ketones 6.
(1R,2S)-[2-(2-F u r yl)cyclop r op yl]m eth yl Ben zoa te (9a ).
To a stirred solution of alcohol 8a (0.1 g, 0.725 mmol) were
added benzoyl chloride (0.174 mL, 1.5 mmol), triethylamine
(0.209 mL, 1.5 mmol), and a catalytic amount of DMAP. After
stirring at 25 °C for 14 h, the mixture was hydrolyzed with
NaHCO3 (10%) and extracted with Et2O (3 × 10 mL). The
solvents were distilled (0.1 mmHg), and the crude product
mixture was subjected to flash column chromatography over
silica gel (hexane:AcOEt, 15:1) to provide pure ester 9a as a
colorless oil: Rf 0.375 (Hex:AcOEt, 10:1); [R]293 ) +37.2 (c
D
0.825, CHCl3); 1H NMR δ 0.9-1.1 (m, 2 H), 1.6-1.7 (m, 1 H),
1.9-2.0 (m, 1 H), 4.25 (d, J ) 7.0 Hz, 2 H), 5.95 (dd, J ) 0.5,
3.2 Hz, 1 H), 6.2 (dd, J ) 1.9, 3.2 Hz, 1 H), 7.2 (d, J ) 1.9 Hz,
1 H), 7.3-7.6 (m, 3 H), 8.0-8.1 (m, 2 H); 13C NMR δ 11.7, 14.9,
19.1, 27.6, 103.9, 110.2, 128.3, 129.5, 130.1, 132.9, 140.5, 155.2,
166.5; IR (neat) 1715, 1096, 1047 cm-1; HRMS calcd for
C15H14O3 242.094 294, found 242.094 790; MS m/z 242 (M+,
38), 136 (17), 129 (66), 105 (100), 91 (30), 77 (48).
Br om om et h yl (1S,2S)-2-p h en ylcyclop r op yl k et on e
(6b): colorless oil; Rf 0.31 (Hex:AcOEt, 10:1); [R]293D ) +321.2
1
(c 0.55, CHCl3); H NMR δ 1.55 (ddd, J ) 4.3, 6.8, 8.1 Hz, 1
Gen er a l P r oced u r e for th e P r ep a r a tion of Br om ocy-
clop r op ylca r ben e Com p lexes 13. To a -78 °C stirred
solution of vinylcarbene complex 1 or 10 (1 mmol) and
dibromomethane (0.11 mL, 1.5 mmol) in Et2O (20 mL) was
H), 1.75 (ddd, J ) 4.3, 5.2, 9.1 Hz, 1 H), 2.45 (ddd, J ) 4.0,
5.2, 8.1 Hz, 1 H), 2.6 (ddd, J ) 4.0, 6.8, 9.1 Hz, 1 H), 4.05 (s,
2 H), 7.1-7.4 (m, 5 H); 13C NMR δ 19.9, 30.2, 30.7, 34.8, 126.1,

Synthesis of Chiral Substituted Cyclopropanes
J . Org. Chem., Vol. 62, No. 20, 1997 6875
added LDA [prepared from MeLi (1 mL of 1.5 M solution in
Et2O, 1.5 mmol) and diisopropylamine (0.21 mL, 1.5 mmol) in
Et2O (5 mL)] dropwise over 5 min. After stirring at -78 °C
for 5 min, the mixture was allowed to warm to room temper-
ature and the reaction quenched with silica gel (ca. 2 g). The
solvents were distilled (0.1 mmHg), and the residue was
subjected to flash column chromatography over silica gel
(hexane:AcOEt, 40:1) to provide cyclopropylcarbene complexes
13.
128.9, 134.3, 171.7; IR (neat) 1730 cm-1; HRMS calcd for
C11H11BrO2 253.994 253, found 253.994 215; MS m/z 256 (M+
+ 2, 21), 224 (M+, 21), 197 (58), 195 (65), 175 (67), 131 (20),
116 (38), 115 (100).
(1S,2R,3S)-2-Br om o-3-p h en ylcyclop r op yl Meth yl Ke-
ton e (15). This compound was prepared, according to the
general procedure described above for compounds 5, from
chiral cyclopropylcarbene complex 13c (0.47 g, 0.75 mmol).
Purification on silica gel (hexane:AcOEt, 40:1) allowed to
recover chiral auxiliary and provided pure ketone 5c as a
colorless oil: Rf 0.28 (Hex:CH2Cl2, 2:1); [R]293D ) +42.0 (c 0.65,
P e n t a c a r b o n y l{[(1R *,2S *,3R *)-2-b r o m o -3-p h e n y l-
cyclop r op yl]m et h oxym et h ylid en e}ch r om iu m (0) (13a ):
1
1
yellow oil; Rf 0.35 (Hex:AcOEt, 10:1); H NMR δ 3.3 (dd, J )
CHCl3); H NMR δ 2.45 (s, 3 H), 2.75 (dd, J ) 3.8, 6.0 Hz, 1
6.0, 8.1 Hz, 1 H), 3.9 (dd, J ) 3.7, 8.1 Hz, 1 H), 4.15 (dd, J )
3.7, 6.0 Hz, 1 H), 4.9 (s, 3 H), 7.2-7.4 (m, 5 H); 13C NMR δ
34.0, 39.8, 55.3, 66.0, 127.6, 128.2, 128.7, 124.4, 215.0, 223.0,
348.6; IR (neat) 2062, 1931 cm-1; HRMS calcd for C16H11BrCrO6
429.914 585, found 429.912 646; MS m/z 432 (M+ + 2, 25), 430
(M+, 25), 404 (13), 402 (13), 320 (90), 318 (91), 292 (20), 159
(39), 128 (75), 115 (100), 105 (30), 57 (25), 52 (32).
H), 2.95 (dd, J ) 6.0, 8.1 Hz, 1 H), 3.7 (dd, J ) 3.8, 8.1 Hz, 1
H), 7.25-7.5 (m, 5 H); 13C NMR δ 29.8, 31.3, 34.0, 36.4, 127.9,
128.1, 128.8, 134.6, 204.9; IR (neat) 1730 cm-1; HRMS calcd
for C11H11BrO 237.999 338, found 237.998 288; MS m/z 239
(M+ + 2, <1), 237 (M+, <1), 159 (77), 116 (39), 115 (96), 43
(100).
Br om om eth yl (1R,2S,3R)-2-Br om o-3-p h en ylcyclop r o-
p yl Keton e (16). This compound was prepared, according to
the typical procedure described above for compounds 6, from
chiral cyclopropylcarbene complex 13c (0.47 g, 0.75 mmol).
Purification on silica gel (hexane:AcOEt, 25:1) allowed to
recover chiral auxiliary and provided pure ketone 16 as a white
crystalline solid: Rf 0.30 (Hex:AcOEt, 10:1); mp 55-57 °C;
P e n t a c a r b o n y l{[(1R *,2R *,3S *)-2-b r o m o -3-p h e n y l-
cyclopr opyl]m eth oxym eth yliden e}tu n gsten (0) (13b): yel-
low oil; Rf 0.275 (Hex:AcOEt, 20:1); 1H NMR δ 3.3 (dd, J )
6.0, 8.2 Hz, 1 H), 3.9 (dd, J ) 3.4, 8.2 Hz, 1 H), 4.2 (dd, J )
3.4, 6.0 Hz, 1 H), 4.6 (s, 3 H), 7.3-7.5 (m, 5 H); 13C NMR δ
33.5, 39.7, 58.8, 69.6, 127.7, 128.3, 128.8, 134.4, 197.0, 203.3,
322.6; IR (neat) 2070, 1915 cm-1; HRMS calcd for C16H11BrO6W
561.923 003, found 561.923 604; MS m/z 562 (M+, 16), 483 (M+
- Br, 49), 427 (34), 424 (51), 409 (68), 407 (95), 356 (86), 298
(75), 159 (68), 128 (70), 115 (100), 91 (30). Anal. Calcd for
C16H31BrO6W: C, 34.13; H, 1.97. Found: C, 34.25; H, 1.94.
P e n t a ca r b on yl{[(1S,2R,3S)-2-b r om o-3-p h e n ylcyclo-
p r o p y l ] [ ( ( 1 R , 3 R , 4 S ) - 8 - p h e n y l m e n t h y l ) o x y ] -
m eth ylid en e}ch r om iu m (0) (13c): yellow oil; Rf 0.56 (Hex:
AcOEt, 20:1); 1H NMR δ 0.8-2.1 (m, 17 H), 2.45 (dd, J ) 6.4,
8.2 Hz, 1 H), 3.3 (dd, J ) 3.4, 8.2 Hz, 1 H), 4.0 (dd, J ) 3.4,
6.4 Hz, 1 H), 5.3 (td, J ) 3.9, 10.7 Hz, 1 H), 7.1-7.5 (m, 10 H);
13C NMR δ 21.6, 26.1, 26.6, 27.7, 31.0, 34.2, 34.8, 36.6, 39.7,
44.2, 51.6, 56.5, 93.0, 125.1, 125.6, 127.2, 128.0, 128.1, 129.2,
[R]293 ) +45.7 (c 0.75, CHCl3); 1H NMR δ 3.0-3.05 (m, 2 H),
D
3.75 (dd, J ) 5.1, 6.8 Hz, 1 H), 4.1 (AB system, J ) 12.4 Hz,
2 H), 7.25-7.4 (m, 5 H); 13C NMR δ 30.4, 34.2, 34.6, 35.2, 127.6,
128.2, 128.9, 134.1, 198.6; IR (neat) 1705 cm-1; HRMS calcd
for C11H10BrO 236.991 513, found 236.991 394; MS m/z 316
(M+, <1), 239 (M+ + 2 - Br, 81), 237 (M+ - Br, 81), 197 (52),
195 (54), 158 (36), 129 (41), 116 (85), 115 (100). Anal. Calcd
for C11H10Br2O: C, 41.55; H, 3.17. Found: C, 41.45; H, 3.15.
Ack n ow led gm en t. We gratefully acknowledge sup-
port from DGICYT (grants PB92-1005 and PB93-0330).
Pablo L. Bernad, J r., thanks II Pan Regional de Inves-
tigacio´n del Principado de Asturias for a predoctoral
fellowship. The authors are also grateful to Dr. P.
Bernad (Servicio de Espectrometr´ıa de Masas, Univer-
sidad de Oviedo) for spectroscopic mass determination.
135.0, 150.4, 216.1, 223.1, 344.6; IR (neat) 2060, 1937 cm-1
;
HRMS calcd for C31H31BrCrO6 630.074 943, found 630.071 150;
MS m/z 632 (M+ + 2, 19), 630 (19), 548 (21), 546 (21), 119 (100),
105 (37), 91 (23). Anal. Calcd for C31H31BrCrO6: C, 58.96;
H, 4.95. Found: C, 58.90; H, 4.88.
Meth yl (1R*,2R*,3S*)-2-Br om o-3-p h en ylcyclop r op a n -
eca r boxyla te (14). This compound was prepared, according
to the general procedure described above for compounds 7,
from chiral cyclopropylcarbene complex 13a (0.43 g, 1 mmol)
to provide pure ester 14 as a colorless oil: Rf 0.37 (Hex:AcOEt,
10:1); 1H NMR δ 2.45 (dd, J ) 3.8, 6.3 Hz, 1 H), 2.95 (dd, J )
6.3, 8.1 Hz, 1 H), 3.5 (dd, J ) 3.8, 8.1 Hz, 1 H), 3.8 (s, 3 H),
7.2-7.4 (m, 5 H); 13C NMR δ 27.8, 28.8, 31.6, 52.3, 127.4, 128.1,
Su p p or tin g In for m a tion Ava ila ble: Copies of the 13C
NMR spectra for all compounds (16 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O9708708