11492
J. Am. Chem. Soc. 2001, 123, 11492-11493
A Versatile New Method for the Synthesis of
Cyclopentenones via an Unusual Rhodium-Catalyzed
Intramolecular Trans Hydroacylation of an Alkyne
Ken Tanaka and Gregory C. Fu*
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, Massachusetts 02139
ReceiVed August 7, 2001
Because cyclopentenones serve both as key intermediates in
the synthesis of a wide array of significant bioactive compounds
(e.g., prostaglandins1) and as interesting natural products in their
own right (e.g., jasmone2 and pentenomycins3), the development
of efficient methods for their construction constitutes an important
ongoing challenge. Of the existing approaches to the synthesis
of cyclopentenones, the Pauson-Khand reaction is perhaps the
most well-known.4 This powerful method does, however, suffer
from certain deficiencies, including poor regioselectivity in the
incorporation of the olefin and modest yield in reactions of
unstrained or hindered olefins, as well as internal alkynes. As a
consequence of these considerations, the intramolecular Pauson-
Khand reaction, which furnishes bicyclic compounds, has been
more widely applied than the intermolecular process.
Figure 1. A possible pathway for metal-catalyzed intramolecular
hydroacylations of 4-alkynals.
of 4-alkynals is the need, if the process follows a pathway
analogous to the reactions of 4-alkenals, for a trans addition of a
metal hydride to an alkyne (Figure 1).10
The transition metal-catalyzed intramolecular hydroacylation
of 4-alkenals has become a well-established method for producing
cyclopentanones (eq 1).5-9 In contrast, the corresponding reaction
of 4-alkynals, which are readily available through 1,4-addition
of alkynylmetals to R,â-unsaturated aldehydes, to generate
cyclopentenones has not been described; in fact, Larock has noted
that, under conditions in which 4-alkenals undergo Rh(PAr3)3-
Cl-catalyzed cyclization, a 4-alkynal furnishes no product.6b One
potential difficulty in achieving intramolecular hydroacylations
During a recent investigation of rhodium-catalyzed isomeriza-
tions of allylic alcohols to aldehydes,11 while attempting to convert
allylic alcohol 1 to 4-alkynal 2, we obtained a small amount of
cyclopentenone 3, presumably via 2 (eq 3). In view of the lack
of precedent for such an intramolecular hydroacylation, we
decided to pursue the development of this unanticipated side
reaction into a versatile new route to cyclopentenones.
(1) For reviews, see: (a) Noyori, R.; Suzuki, M. Science 1993, 259, 44-
45. (b) Straus, D. S.; Glass, C. K. Med. Res. ReV. 2001, 21, 185-210. (c)
Corey, E. J. Angew. Chem., Int. Ed. Engl. 1991, 30, 455-465.
(2) For leading references to jasmone and its derivatives, see: (a) Dobbs,
D. A.; Vanhessche, K. P. M.; Brazi, E.; Rautenstrauch, V.; Lenoir, J.-Y.; Geneˆt,
J.-P.; Wiles, J.; Bergens, S. H. Angew. Chem., Int. Ed. 2000, 39, 1992-1995.
(b) Fra`ter, G.; Bajgrowicz, J. A.; Kraft, P. Tetrahedron 1998, 54, 7633-
7703.
(3) For leading references, see: Seepersaud, M.; Al-Abed, Y. Tetrahedron
Lett. 2000, 41, 4291-4293.
(4) For reviews, see: (a) Schore, N. E. Org. React. 1991, 40, 1-90. (b)
Brummond, K. M.; Kent, J. L. Tetrahedron 2000, 56, 3263-3283. (c) Chung,
Y. K. Coord. Chem. ReV. 1999, 188, 297-341.
(5) For examples of intramolecular hydroacylations of 4-alkenals in the
presence of stoichiometric Rh(PPh3)3Cl, see: Sakai, K.; Ide, J.; Oda, O.;
Nakamura, N. Tetrahedron Lett. 1972, 1287-1290.
(6) For examples of intramolecular hydroacylations of 4-alkenals in the
presence of catalytic amounts of rhodium complexes, see: (a) Lochow, C.
F.; Miller, R. G. J. Am. Chem. Soc. 1976, 98, 1281-1283. (b) Larock, R. C.;
Oertle, K.; Potter, G. F. J. Am. Chem. Soc. 1980, 102, 190-197. (c) Sakai,
K.; Ishiguro, Y.; Funakoshi, K.; Ueno, K.; Suemune, H. Tetrahedron Lett.
1984, 25, 961-964. (d) Fairlie, D. P.; Bosnich, B. Organometallics 1988, 7,
936-945.
(7) For examples of catalytic enantioselective intramolecular hydroacyla-
tions of 4-alkenals, see: (a) James, B. R.; Young, C. G. J. Chem. Soc., Chem.
Commun. 1983, 1215-1216. James, B. R.; Young, C. G. J. Organomet. Chem.
1985, 285, 321-332. (b) Taura, Y.; Tanaka, M.; Funakoshi, K.; Sakai, K.
Tetrahedron Lett. 1989, 30, 6349-6352. Tanaka, M.; Imai, M.; Fujio, M.;
Sakamoto, E.; Takahashi, M.; Eto-Kato, Y.; Wu, X. M.; Funakoshi, K.; Sakai,
K.; Suemune, H. J. Org. Chem. 2000, 65, 5806-5816. (c) Barnhart R. W.;
Wang, X.; Noheda, P.; Bergens, S. H.; Whelan, J.; Bosnich, B. J. Am. Chem.
Soc. 1994, 116, 1821-1830. Bosnich, B. Acc. Chem. Res. 1998, 31, 667-
674 and references therein.
(8) For examples of intramolecular hydroacylations of 4-alkenals in the
presence of catalytic amounts of ruthenium complexes, see: Eilbracht, P.;
Gersmeier, A.; Lennartz, D.; Huber, T. Synthesis 1995, 330-334.
(9) For examples of intramolecular hydroacylations of 4-alkenals in the
presence of catalytic amounts of cobalt complexes, see: (a) Vinogradov, M.
G.; Tuzikov, A. B.; Nikishin, G. I.; Shelimov, B. N.; Kazansky, V. B. J.
Organomet. Chem. 1988, 348, 123-134. (b) Lenges, C. P.; Brookhart, M. J.
Am. Chem. Soc. 1997, 119, 3165-3166.
Among the phosphines (e.g., binap, dppf, and dcpe) and
solvents (e.g., CH2Cl2, THF, benzene, and CH3NO2) that we have
examined, the combination of Rh/dppe and acetone has proved
to be the most effective. Under these conditions, we can achieve
the intramolecular hydroacylation of a broad range of 4-alkynals
to produce cyclopentenones in good yield (eq 4).
(10) While attempting to decarbonylate an aldehyde with RhCl(PPh3)3,
Nicolaou observed a novel intramolecular hydroacylation of a 5-alkynal to
generate a cyclohexenone (78% yield based on 50% conversion). To the best
of our knowledge, this single example (a stoichiometric process: 2.5 equiv
of RhCl(PPh3)3 were used, relative to isolated cyclohexenone) is the only report
to date of an intramolecular hydroacylation of an acetylenic aldehyde. See:
Nicolaou, K. C.; Gross, J. L.; Kerr, M. A. J. Heterocycl. Chem. 1996, 33,
735-746.
(11) Tanaka, K.; Qiao, S.; Tobisu, M.; Lo, M. M.-C.; Fu, G. C. J. Am.
Chem. Soc. 2000, 122, 9870-9871.
10.1021/ja011907f CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/25/2001