J. Am. Chem. Soc. 1997, 119, 10225-10226
10225
Scheme 1
Totally Stereocontrolled Intermolecular
Pauson-Khand Reactions of N-(2-Alkynoyl)
Sultams
S´ılvia Fonquerna, Albert Moyano,* Miquel A. Perica`s,* and
Antoni Riera
Unitat de Recerca en S´ıntesi Asime`trica
Departament de Qu´ımica Orga`nica
UniVersitat de Barcelona, Mart´ı i Franque`s, 1-11
08028-Barcelona, Spain
ReceiVed March 21, 1997
The convergent assembly of cyclopentenones from an alkene
and an acetylene-dicobalt hexacarbonyl complex, usually
known as the Pauson-Khand reaction, has become a well-
established synthetic method.1 To the ever-increasing use of
this process have contributed both recent discoveries of effective
promoters of the reaction2 and the development of catalytic3
and of asymmetric versions. Two main strategies have been
used in enantioselective approaches to the reaction, involving
the transfer of chirality either from dicobalt hexacarbonyl
complexes possessing a disymmetric C2Co2 core4 or from
removable chiral auxiliaries attached to the cyclization com-
ponents.5 Only very recently the first examples of an enanti-
oselective catalytic intramolecular Pauson-Khand type process
based on chiral titanocene complexes have been disclosed.6 In
the past few years, we have shown that good levels of
diastereoselectivity can be attained in the intramolecular Pau-
son-Khand reactions of enol ethers5a or alkoxyacetylenes5b
derived from chiral alcohols and that the resulting cycloadducts
can be applied to the enantioselective synthesis of natural
products.5a,e,f In the extension of this approach to intermolecular
Pauson-Khand reactions, the best results to date involve the
use of the alkoxyethyne-dicobalt hexacarbonyl complex derived
from 10-(methylthio)isoborneol, which can be converted to an
unstable, sulfur-chelated dicobalt pentacarbonyl complex whose
low-temperature reaction with norbornadiene takes place with
92% diastereomeric excess (de).5c In the absence of chelation
effects, however, intermolecular cyclizations of chiral alkoxy-
acetylenes are much less stereoselective.5d Herein, we report
that exceptionally high leVels of regio- and stereoselectiVity can
be easily achieVed by pure steric control and under standard
reaction conditions in the intermolecular Pauson-Khand reac-
tion of N-(2-alkynoyl) deriVatiVes of chiral oxazolidinones and
sultams, especially for Oppolzer’s 10,2-camphorsultam.
obtained in the Pauson-Khand reaction of the derived
2-alkynoates are greater than those observed for the correspond-
ing O-alkyl ynol ethers, even though in the former derivatives
the stereogenic centers of the auxiliary are farther from the
acetylene moiety.7 We reasoned that this could be due to a
restricted conformational mobility of the carboxyl group in the
dicobalt hexacarbonyl complexes and that one could expect
higher degrees of stereoselectivity by replacing the ester linkage
by a less-mobile amide bond. To test these ideas, we prepared
a series of 2-alkynoyl derivatives of the homochiral 2-oxazo-
lidinones a-c and of (+)-10,2-camphorsultam (d) (Scheme 1).
The requisite alkynes (compounds 1-3) could be obtained in
good yields by nucleophilic attack of the lithium salt (or lithium
chloride complex for 3d) of the chiral auxiliary on a pivalic-
2-alkynoic mixed anhydride.8 The intermolecular Pauson-
Khand cocyclization of these electron-deficient alkynes with
norbornadiene9 was next investigated (Scheme 1). The acety-
lene-dicobalt hexacarbonyl complexes were readily obtained
by treatment of a solution of the alkyne with a slight excess of
dicobalt octacarbonyl and, without isolation, were reacted with
norbornadiene, using either the classical thermal conditions1 or
chemical activation,2a,b to give in all cases the exo-adducts (4-
7) in high yield. The reactions of both the phenylpropiolic (1a-
d) and the (trimethylsilyl)propiolic acid derivatives (2b,d) turned
out to be completely regioselective, leading exclusively to the
3-carbamoyl cyclopentenones 4 and 5, respectively. The
reactions of the 2-butynoic acid derivatives 3a-d were much
less regioselective, the 1,3-dicarbonylic regioisomers 7a-d also
being obtained in substantial amounts and with low stereose-
lectivity.
The original impetus for this research came from the
observation that for certain chiral alcohols the stereoselectivities
(1) For a recent review on the Pauson-Khand reaction, see: Schore, N.
E. In ComprehensiVe Organometallic Chemistry II; Hegedus, L. S., Ed.;
Elsevier: Oxford, 1995; Vol. 12, pp 703-739.
(2) (a) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetrahedron Lett.
1990, 31, 5289-5292. (b) Jeong, N.; Chung, Y. K.; Lee, B. Y.; Lee, S. H.;
Yoo, S.-E. Synlett 1991, 204-206.
(3) (a) Pagenkopf, B. L.; Livinghouse, T. J. Am. Chem. Soc. 1996, 118,
2285-2286. (b) Chung, Y. K.; Lee, N. Y. Tetrahedron Lett. 1996, 37,
3145-3148 and references therein.
(4) (a) Park, H.-J.; Lee, B. Y.; Kang, Y. K.; Chung, Y. K. Organome-
tallics 1995, 14, 3104-3107. (b) Hay, A. M.; Kerr, W. J.; Kirk, G. G.;
Middlemiss, D. Organometallics 1995, 14, 4986-4988 and references
therein.
The results on the formation of the 3-carbamoyl derivatives
4-6 are summarized in Table 1. We first discuss the cyclization
of the phenylpropiolyl derivatives 1a-d. In addition to the
unusually mild reaction conditions, the high yields, and the
complete regioselectivity, the stereoselectivity of the process
is remarkable and appears to be extremely sensitive to the
(5) (a) Castro, J.; So¨rensen, H.; Riera, A.; Morin, C.; Moyano, A.; Perica`s,
M. A.; Greene, A. E. J. Am. Chem. Soc. 1990, 112, 9388-9389. (b)
Verdaguer, X.; Moyano, A.; Perica`s, M. A.; Riera, A.; Greene, A. E.;
Piniella, J.; Alvarez-Larena, A. J. Organomet. Chem. 1992, 433, 305-
310. (c) Verdaguer, X.; Moyano, A.; Perica`s, M. A.; Riera, A.; Bernardes,
V.; Greene, A. E.; Alvarez-Larena, A.; Piniella, J. F. J. Am. Chem. Soc.
1994, 116, 2153-2154. (d) Bernardes, V.; Verdaguer, X.; Kardos, N.; Riera,
A.; Moyano, A.; Perica`s, M. A.; Greene, A. E. Tetrahedron Lett. 1994, 35,
575-578. (e) Castro, J.; Moyano, A.; Perica`s, M. A.; Riera, A.; Greene,
A. E.; Alvarez-Larena, A.; Piniella, J. F. J. Org. Chem. 1996, 61, 9016-
9020. See also: (f) Stolle, A.; Becker, H.; Salau¨n, J.; de Meijere, A.
Tetrahedron Lett. 1994, 35, 3521-3524.
(7) Fonquerna, S.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron
1995, 51, 4239-4254.
(8) Ho, G.-J.; Mathre, D. J. J. Org. Chem. 1995, 60, 2271-2273 and
references therein.
(9) For derivatives 1a-d and 3a-d, all of the reactions reported in Table
1 gave essentially the same yields and isomer ratios upon replacement of
norbornadiene with norbornene.
(6) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 11688-
11689.
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