12610
J. Am. Chem. Soc. 2000, 122, 12610-12611
3 f 4.1b,c,e A proposed catalytic cycle is depicted in Scheme 2.
Initially, the Rh(I) catalyst oxidatively inserts into the aldehyde
C-H bond of 3, affording acyl-Rh(III) intermediate 5. Intramo-
lecular hydrometalation of 5 affords the six-membered Rh-
metallacycle 6. Two pathways are accessible to 6. Reductive
elimination (pathway A) is usually observed with intermediates
related to 6, delivering cyclopentanones (e.g. 7). The presence
of a cyclopropane ring adjacent to Rh(III) in 6 provides access
to pathway B leading to ring fragmentation and isomerization
affording nine-membered Rh-metallacycle 8. Intermediate 8 would
be expected to undergo reductive elimination to generate 4-
cycloocten-1-one 4. Although there is precedent for ring opening
of cyclopropanes adjacent to Rh(III),4,6,7 questions remained
regarding the extrapolation to intermediate 6, the relative rates
of pathway A versus pathway B, and the influence of the catalyst
structure on these relative rates. An additional concern was the
potential for Rh(I)-catalyzed ring opening of the vinyl cyclopro-
pane prior to C-H insertion.8
Synthesis of Cyclooctenones Using Intramolecular
Hydroacylation
Allen D. Aloise, Mark E. Layton, and Matthew D. Shair*
Department of Chemistry and Chemical Biology
HarVard UniVersity, Cambridge, Massachusetts 02138
ReceiVed September 8, 2000
Reactions that involve insertion of transition metal-based
catalysts into C-H bonds and the subsequent creation of ring
structures represent an underdeveloped area of organic synthesis.
The Rh(I)-catalyzed cyclization of 4-pentenals to cyclopentanones
(Scheme 1, 1 f 2), an intramolecular hydroacylation, is an
example of such a reaction.1 First reported 28 years ago by Sakai
using RhCl(Ph3P)3,1a this reaction has remained largely limited
to the synthesis of five-membered rings2 due to competitive
decarbonylation as ring size increases and rates of cyclization
decrease. Application of this reaction to the synthesis of medium
rings such as cyclooctenones would be a useful transformation;3
however, it is inefficient due to the prohibitively slow cyclization
rates of eight-membered rings. We hypothesized that the intramo-
lecular hydroacylation reaction could be extended to the synthesis
of cyclooctenones by strategic placement, in the starting material,
of a cyclopropane ring capable of fragmentation (Scheme 1, 3 f
4). Recently, a similar strategy was used by Wender4 and Trost5
in transition metal-catalyzed [5+2] cycloadditions, affording
seven-membered rings. This contribution describes the extension
of intramolecular hydroacylation to the synthesis of eight-
membered rings using the strategy outlined in Scheme 1.
Scheme 2
Scheme 1
Compound 9 was constructed to test our hypothesis (Scheme
3).9 Treatment of 9 with RhCl(Ph3P)3 did not result in any
intramolecular hydroacylation products (entry 1). Addition of
2-amino-3-picoline, an additive known to facilitate hydroacylation
by the formation of a pyridylimine intermediate,10 delivered both
cyclooctenone 10 and cyclopentanone 11 in a 1:6 ratio (entry 2).
Use of [Rh(dppe)]ClO4, a cationic Rh(I) catalyst developed by
Bosnich for intramolecular hydroacylation,1d switched the selec-
tivity of the reaction to favor eight-membered ring 10 over 11 in
a ratio of 9.4:1 (entry 3). However, decarbonylation was observed
and the yield of 10 was limited to 47% (entry 3). A catalyst with
a more dissociated anion, [Rh(dppe)]OTf, delivered 10 in 50%
yield to the exclusion of 11 (entry 4). Attempts to use lower
catalyst loadings led to diminished yields due to low conversion,
although reactions that were performed with 20 mol % catalyst
loading under an atmosphere of ethylene produced less decarbo-
The thoroughly investigated mechanism of the intramolecular
hydroacylation reaction provides a basis for the conversion of
(1) (a) Sakai, K.; Ide, J.; Oda, O.; Nakamura, N. Tetrahedron Lett. 1972,
1287. (b) Campbell, R. E., Jr.; Lochow, C. F.; Vora, K. P.; Miller, R. G. J.
Am. Chem. Soc. 1980, 102, 5824. (c) Larock, R. C.; Oertle, K.; Potter, G. J.
J. Am. Chem. Soc. 1980, 102, 190. (d) Fairlie, D. P.; Bosnich, B. Organo-
metallics 1988, 7, 936. (e) Fairlie, D. P.; Bosnich, B. Organometallics 1988,
7, 946. (f) Barnhart, R. W.; Wang, X.; Noheda, P.; Bergens, S. H.; Whelan,
J.; Bosnich, B. J. Am. Chem. Soc. 1994, 116, 1821. (g) Lenges, C. P.;
Brookhart, M. J. Am. Chem. Soc. 1997, 119, 3165. (h) Barnhart, R. W.;
McMorran, D. A.; Bosnich, B. Chem. Commun. 1997, 589. (i) Barnhart, R.
W.; McMorran, D. A.; Bosnich, B. Inorg. Chim. Acta 1997, 263, 1. (j) Bosnich,
B. Acc. Chem. Res. 1998, 31, 667. (k) Fujio, M.; Tanaka, M.; Wu, X.;
Funakoshi, F.; Sakai, K.; Suemune, H. Chem. Lett. 1998, 881. (l) Tanaka,
M.; Imai, M.; Fujio, M.; Sakamoto, E.; Takahashi, M.; Eto-Kato, Y.; Wu, X.;
Funakoshi, K.; Sakai, K.; Suemune, H. J. Org. Chem. 2000, 65, 5806.
(2) For the synthesis of a six-membered ring via intramolecular hydroa-
cylation, see: Gable, K. P.; Benz, G. A. Tetrahedron Lett. 1991, 32, 3473.
(3) For a recent review of progress in the construction of cyclooctanoid
systems see: Mehta, G.; Vishwakarma, S. Chem. ReV. 1999, 99, 881.
(4) (a) Wender, P. A.; Takahashi, H.; Witulski, B. J. Am. Chem. Soc. 1995,
117, 4720. (b) Wender, P. A.; Husfeld, C. O.; Langkopf, E.; Love, J. A. J.
Am. Chem. Soc. 1998, 120, 1940. (c) Wender, P. A.; Glorius, F.; Husfeld, C.
O.; Langkopf, E.; Love, J. A. J. Am. Chem. Soc. 1999, 121, 5348. (d) Wender,
P. A.; Dyckman, A. J.; Husfeld, C. O.; Kadereit, D.; Love, J. A. J. Am. Chem.
Soc. 1999, 121, 10442.
(6) Jun, C.-H.; Kang, J.-B.; Lim, Y.-G. Bull. Korean Chem. Soc. 1991,
12, 251.
(7) For the fragmentation of three- and four-membered rings adjacent to
acyl-Rh(III) bonds, see: Murakami, M.; Takahashi, K.; Amii, H.; Ito, Y. J.
Am. Chem. Soc. 1997, 119, 9307.
(8) Khusnutdinov, R. I.; Dzhemilev, U. M. J. Organomet. Chem. 1994,
471, 1 and references therein.
(9) Synthesis and characterization of 9 and all substrates are reported in
the Supporting Information.
(5) (a) Trost, B. M.; Toste, F. D.; Shen, H. C. J. Am. Chem. Soc. 2000,
122, 2379. (b) Trost, B. M.; Shen, H. C. Org. Lett. 2000, 2, 2523.
(10) Jun, C.-H.; Lee, H.; Hong, J.-B. J. Org. Chem. 1997, 62, 1200.
10.1021/ja0055920 CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/30/2000