J . Org. Chem. 2000, 65, 4131-4137
4131
Ch em o- a n d Regioselective Cycloh yd r oca r bon yla tion of r-Keto
Alk yn es Ca ta lyzed by a Zw itter ion ic Rh od iu m Com p lex a n d
Tr ip h en yl P h osp h ite
Bernard G. Van den Hoven, Bassam El Ali,† and Howard Alper*
Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, Canada, K1N 6N5
Received February 18, 2000
R-Keto alkynes react with CO and H2 in the presence of catalytic quantities of the zwitterionic
rhodium complex (η6-C6H5BPh3)-Rh+(1,5-COD) and triphenyl phosphite affording either the 2-,
2(3H)-, or 2(5H)-furanones in 61-93% yields. The cyclohydrocarbonylation is readily accomplished
using substrates containing alkyl, aryl, vinyl, and alkoxy groups at the acetylenic terminal, as
well as a variety of primary, secondary, and tertiary alkyl, aryl, and heteroaryl groups connected
to the ketone functionality. Structural and electronic properties present in the starting materials
mediate the chemo- and regioselectivity of the reaction.
In tr od u ction
Furanones have been of interest for many years due
to their biological activity.1 A variety of transition metal
catalyzed methods have been utilized for the preparation
of γ-lactones including the transition metal catalyzed
cyclocarbonylation of alkenols,2 alkynols,3 alkynes,4 and
alkynoic acids.5 Several of these reactions are of value
for the synthesis of multifunctionalized lactones.
F igu r e 1. Proposed intermediate in Rh4(CO)12-catalyzed
carbocyclization.
tion of chiral furanones from achiral substrates, as found
for the asymmetric hydroformylation of alkenes.6
The cyclocarbonylation of acetylene containing sub-
strates requires high temperatures and pressures for
both palladium3h- (eq 1) and rhodium5a-catalyzed reac-
tions (eq 2). Obstacles have been encountered in attaining
high yields of these highly substituted furanones under
milder temperatures and pressures.3d,k The ability to use
milder conditions may be of importance for the prepara-
† Present address: Department of Chemistry, King Fahd University
of Petroleum and Minerals, Dhahran, Saudi Arabia.
(1) (a) Rao, Y. S. Chem. Rev. 1976, 76, 5. (b) Barton, D.; Nakanishi,
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V.; Cain, R. B. J . Chem. Soc., Perkin Trans. 1 1996, 2111. (d) Handa,
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(2) (a) Alper, H.; Leonard, D. Tetrahedron Lett. 1985, 26, 5639. (b)
Alper, H.; Leonard, D. Chem. Commun. 1985, 511. (c) Alper, H.; Hamel,
N. Chem. Commun. 1990, 135. (d) El Ali, B.; Okuro, K.; Vasapollo, G.;
Alper, H. J . Am. Chem. Soc. 1996, 118, 4264. (e) Brunner, M.; Alper,
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Previous work with Rh4(CO)12 utilizinginternalalkynes5a,c
postulated a dicarbonyl-metal complex as a reaction
intermediate (Figure 1). Here, R1 and R2 were alkyl or
aromatic groups. A conceivably similar intermediate may
result from the hydroformylation of an R-keto alkyne if
the carbonylation step occurred at the triple bond carbon
closest to R2.
The use of an achiral substrate, an alkynone, would
create a new chiral center in the preparation of fura-
nones. A phase transfer nickel catalyst was used for the
cyclohydrocarbonylation of R-keto alkynes in 1995.7
Although the yields were low, ring cleavage occurred to
form alkenoic acids. In addition, in 1996, tetrasubstituted
3(2H)-furanones were readily prepared in moderate
yields from 4-hydroxyalk-2-ynones and alkyl halides
using tandem CO2 addition-elimination conditions.8
In recent years, a better understanding of the hydro-
formylation of internal alkynes to form R,â-unsaturated
(3) (a) Cowell, A.; Stille, J . K. Tetrahedron Lett. 1979, 133. (b) Inoue,
Y.; Ohuchi, K.; Yen, I.-F.; Imaizumi, S. Bull. Chem. Soc. J pn. 1989,
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Matsushita, K.; Komori, T.; Oi, S.; Inoue, Y. Tetrahedron Lett. 1994,
35, 5889. (e) Gabriele, B.; Costa, M.; Salerno, G.; Chiusoli, G. P. Chem.
Commun. 1994, 1429. (f) Mandai, T.; Tsujiguchi, Y.; Matsuoka, S.;
Saito, S.; Tsuji, J . J . Organomet. Chem. 1995, 488, 127. (g) Xiao, W.-
J .; Alper, H. J . Org. Chem. 1997, 62, 3422. (h) Yu, W.-Y.; Alper, H. J .
Org. Chem. 1997, 62, 5684. (i) Gabriele, B.; Salerno, G.; De Pascali,
F.; Costa, M.; Chiusoli, G. P. J . Chem. Soc., Perkin Trans. 1 1997, 147.
(j) Allevi, P.; Ciuffreda, P.; Anastasia, M. Tetrahedron Asymmetry 1997,
8, 93. (k) Dupont, J .; Donato, A. J . Tetrahedron Asymmetry 1998, 9,
949. (l) Ogawa, A.; Kawabe, K.-I.; Kawakami, J .-I.; Mihara, M.; Hirao,
T. Organometallics 1998, 17, 3111.
(4) Rossi, R.; Bellina, F.; Biagetti, M.; Mannina, L. Tetrahedron Lett.
1998, 39, 7599.
(5) (a) J oh, T.; Doyama, K.; Onitsuka, K.; Shiohara, T.; Takahashi,
S. Organometallics 1991, 10, 2493. (b) Cope´ret, C.; Sugihara, T.; Wu,
G.; Shimoyama, I.; Negishi, E, -I. J . Am. Chem. Soc. 1995, 117, 3422.
(c) Trost, B. M.; Fleming, I. In Comprehensive Organic Synthesis;
Pergamon: Oxford, 1991; Vol. 5, pp 1136-1138.
(6) Agbossou, F.; Carpentier, J .-F.; Mortreux, A. Chem. Rev. 1995,
95, 2485.
(7) Arzoumanian, H.; J ean, M.; Nuel, D.; Cabrera, A.; Gutierrez, J .
L. G.; Rosas, N. Organometallics 1995, 14, 5438.
(8) Kawaguchi, T.; Yasuta, S.; Inoue, Y. Synthesis 1996, 1431.
10.1021/jo000230w CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/01/2000