Enantiomerically pure cyclohexenones by Fe-mediated carbonylation of alkenyl cyclopropanes [22]

Full text of DOI:10.1021/ja994155m

J. Am. Chem. Soc. 2000, 122, 6807-6808
6807
cleavage of bond “b”. We thought that with such an organome-
tallic cleavage the desired product 6 could be preferred, since 6
would have a primary carbon-metal bond, rather than the less-
stable secondary carbon-metal bond of 5.
Enantiomerically Pure Cyclohexenones by
Fe-Mediated Carbonylation of Alkenyl
Cyclopropanes
Douglass F. Taber,* Kazuo Kanai, Qin Jiang, and Gina Bui1
Department of Chemistry and Biochemistry
UniVersity of Delaware, Newark, Delaware 19716
ReceiVed NoVember 29, 1999
We report a general method for the construction of 5-alkyl
cyclohexenones (e.g., 2) of high enantiomeric purity, by ultraviolet
irradiation of enantiomerically pure alkenyl cyclopropanes such
as 1 in the presence of Fe(CO)5.2 Given the many strategies for
the preparation of enantiomerically pure alkenyl cyclopropanes
that are available,3 this promises to be a versatile method for the
construction of cyclohexane derivatives.
Photochemically initated Fe(CO)5 carbonylation of alkenyl
cyclopropanes had been reported,2 but the regioselectivity of the
process had not been explored. The accepted mechanism (Scheme
1),2d however, presented exactly the choice we wanted to set up,
Scheme 1
Most ring-expanding reactions of vinyl cyclopropanes, as
exemplified by the thermal vinyl cyclopropane rearrangement,4
proceed with preferential cleavage of bond “a”, to give the more
stable diradical 3. Unfortunately, cleavage at “a” destroys the
stereogenic centers of the cyclopropane. If preferential cleavage
of bond “b” could be achieved, to give 4, one of the ring
stereogenic centers could be a spectator, and the enantiomeric
purity of the product could be maintained.
We envisioned that an organometallic cleavage, perhaps by
way of initial complexation with the alkene, could lead to either
metallacycle 5, by cleavage of bond “a”, or to metallacycle 6, by
that is, between metallacycle 9 and metallacycle 12. In fact, UV
irradiation with Fe(CO)5 in benzene converted the cyclopropane
1 predominantly to the desired 5-alkyl cyclohexenone 2, the
product from bond “b” cleavage.5,6 In practice, we have found it
convenient to add DBU after the irradiation, to convert the
intermediate products to their more stable conjugated isomers.
While the enone 14 was a minor product from the Fe-mediated
carbonylation of 1, the corresponding enone was the dominant
product from the Fe-mediated carbonylation of 18 (Table 1). We
concluded that 14 was formed by “Fe-H” isomerization of 2, and
thus we tried several different additives to suppress this unwanted
alkene migration. We eventually found that we could minimize
the formation of the isomerized byproduct by running the reaction
in 2-propanol.
* Corresponding author. Telephone: 302-831-2433. Fax: 302-831-6335.
E-mail: taberdf@udel.edu.
(1) Undergradutate research participant.
(2) (a) The photochemical Fe(CO)5-mediated carbonylation of vinyl cy-
clopropanes was first reported in 1970: Sarel, S. Acc. Chem. Res. 1978, 11,
204. For more recent references, see: (b) Khusnutdinov, R. I.; Dzhemilev,
U. M. J. Organomet. Chem. 1994, 471, 1. (c) Schulze, M. M.; Gockel, U.
Tetrahedron Lett. 1996, 37, 357. (d) Schulze, M. M.; Gockel, U. J. Organomet.
Chem. 1996, 525, 155.
(3) For an overview of strategies that could be used for the construction of
alkenyl cyclopropanes of high enantiomeric purity, see: (a) Davies, H. M.
L.; Bruzinski, P. R.; Lake, D. H.; Kong, N.; Fall, M. J. J. Am. Chem. Soc.
1996, 118, 6897. For more recent examples, see: (b) Zhou, S.-M.; Deng,
M.-Z.; Xia, L.-J. Angew. Chem., Int. Ed. 1998, 37, 2845. (c) Lo, M. M.-C.;
Fu, G. C. J. Am. Chem. Soc. 1998, 120, 10270. (d) Charette, A. B.; Juteau,
H.; Lebel, H.; Molinaro, C. J. Am. Chem. Soc. 1998, 120, 11943. (e) Schwarz,
J. B.; Meyers, A. I. J. Org. Chem. 1998, 63, 1619. (f) Temme, O.; Taj, S.-A.;
Andersson, P. G. J. Org. Chem. 1998, 63, 6007. (g) Sakaguchi, K.; Mano,
H.; Ohfune, Y. Tetrahedron Lett. 1998, 39, 4311. (h) Yang, Z.; Lorenz, J. C.;
Shi, Y. Tetrahedron Lett. 1998, 39, 8621. (i) Fox, M. E.; Li, C.; Marino, J.
P., Jr.; Overman, L. E. J. Am. Chem. Soc. 1999, 121, 5467. (j) Dorizon, P.;
Su, G.; Ludvig, G.; Nikitina, L.; Paugam, R.; Ollivier, J.; Salaun, J. J. Org.
Chem. 1999, 64, 4712. (k) Davies, H. M. L.; Panaro, S. A. Tetrahedron Lett.
1999, 40, 5287. (l) Cai, L.; Mahmoud, H.; Han, Y. Tetrahedron: Asymmetry
1999, 10, 411.
(4) For preferential bond “a” opening of alkenyl cyclopropanes, see: (a)
Feldman, K. S.; Romanelli, A. L.; Ruckle, R. E., Jr.; Miller, R. F. J. Am.
Chem. Soc. 1988, 110, 3300. (b) Feldman, K. S.; Bervan, H. M.; Romanelli,
A. L.; Parvez, M. J. Org. Chem. 1993, 58, 6851. (c) Feldman, K. S.; Bervan,
H. M.; Weinreb, P. H. J. Am. Chem. Soc. 1993, 115, 11364. (d) Takeda, K.;
Sakurama, K.; Yoshii, E. Tetrahedron Lett. 1997, 38, 3257. (e) Pattenden,
G.; Wiedenau, P. Tetrahedron Lett. 1997, 38, 3647 and references therein.
(5) (a) For an overview of carbonylative diene and enyne cyclometalation,
see: Hegedus, L. S. Transition Metals in the Synthesis of Complex Organic
Molecules, 2nd ed.; University Science Books: Sausalito, 1999. For other
recent references to carbonylative cyclometalation, see: (b) Taber, D. F.;
Wang, Y. J. Am. Chem. Soc. 1997, 119, 22. (c) Zhao, Z.; Ding, Y.; Zhao, G.
J. Org. Chem. 1998, 63, 9285. (d) Negishi, E.-I.; Montchamp, J.-L.; Anastasia,
L.; Elizarov, A.; Choueiry, D. Tetrahedron Lett. 1998, 39, 2503. (e) Shiu,
Y.-T.; Madhushaw, R. J.; Li, W.-T.; Lin, Y.-C.; Lee, G.-H.; Peng, S.-M.;
Liao, F.-L.; Wang, S.-L.; Liu, R.-S. J. Am. Chem. Soc. 1999, 121, 4066.
(6) Concurrently with our work, three other groups reported preferential
metal-mediated bond “b” opening of alkenyl cyclopropanes: (a) Murakami,
M.; Itami, K.; Ubukata, M.; Tsuji, I.; Ito, Y. J. Org. Chem. 1998, 63, 4. (b)
Wender, P. A.; Dyckman, A. J.; Husfield, C. O.; Kadereit, D.; Love, J. A.;
Rieck, H. J. Am. Chem. Soc. 1999, 121, 10442. (c) Trost, B. M.; Toste, F. D.;
Shen, H. J. Am. Chem. Soc. 2000, 122, 2379.
10.1021/ja994155m CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/30/2000

6808 J. Am. Chem. Soc., Vol. 122, No. 28, 2000
Table 1. Carbonylation of Alkenyl Cyclopropanes
Communications to the Editor
Scheme 2
conditions. To explore this, we prepared 1 (Scheme 2) from the
epoxide 27, which is commercially available in high enantiomeric
purity. We were pleased to observe that the product 2 had
maintained8 its enantiomeric purity. Cyclopropane 15 was also
prepared from epoxide 27. The product enone 16 was shown to
be >99% ee by chiral HPLC.9
The Fe(CO)5-mediated cyclocarbonylation of alkenyl cyclo-
propanes described here should be a general method for the
preparation of enantiomerically pure 5-alkylcyclohexenones,
which are key building blocks for natural product synthesis.10 We
are also exploring the application of this method to polycyclic
ring construction.
Acknowledgment. We thank the donors of the Petroleum Research
Fund, administered by the American Chemical Society, for support of
this work. We thank William A. Nugent and Titus A. Jenny for helpful
discussions, and DAISO for a gift of the epoxide 27.
We have made a preliminary exploration of the scope of this
cyclocarbonylation (Table 1). It was apparent that disubstituted
alkenes participated efficiently. The yield with a trisubstituted
alkene was a little lower.7 The examples in Table 1 were carried
out in 2-propanol (0.05 M), using 2 mol equiv of the inexpensive
Fe(CO)5, under one atmosphere of CO pressure, irradiated in
Pyrex tubes in a Rayonet apparatus. With 10 mol % of Fe(CO)5
(CO atmosphere) the yield of 22 was 77%, and with 5 mol % of
Fe(CO)5 the yield of 22 was 73%. With 2 mol equiv of Fe(CO)5
and an N2 atmosphere the yield of 22 was 57%.
Supporting Information Available: Spectroscopic data for all new
compounds (PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
JA994155M
(8) Carda, M.; Van der Eycken, J.; Vandewalle, M. Tetrahedron: Asym-
metry 1990, 1, 17.
(9) To make this determination, ent-16 was prepared from enantiomerically
pure 2 by addition of CH3MgBr followed by PCC oxidation. On an analytical
Chiralcel OD column, eluting with 95:5 hexanes/2-propanol at 1.0 mL/min,
16 (13.5 min) and ent-16 (12.3 min) showed baseline resolution.
(10) For leading references to alternative methods for the preparation of
5-alkylcyclohexenones of high enantiomeric purity, see: (a) Asaoka, M.;
Shima, K.; Takei, H. Tetrahedron Lett. 1987, 28, 5669. (b) Schwarz, J. B.;
Devine, P. N.; Meyers, A. I. Tetrahedron 1997, 53, 8795. (c) Hareau, G. P.-
J.; Koiwa, M.; Hikichi, S.; Sato, F. J. Am. Chem. Soc. 1999, 121, 3640. (d)
Sarakinos, G.; Corey, E. J. Org. Lett. 1999, 1, 811.
The appearance of the alkene-migrated product 14 suggested
that 2 might have undergone racemization under the reaction
(7) The starting cyclopropanes were mixtures of stereoisomers. Each of
the stereoisomers appeared to participate efficiently in the carbonylation
reaction.