A diastereoselective metal-catalyzed [2 + 2] cycloaddition of bis-enones [5]

Full text of DOI:10.1021/ja010800p

6716
J. Am. Chem. Soc. 2001, 123, 6716-6717
A Diastereoselective Metal-Catalyzed [2 + 2]
2
presence of 10 mol % Co(dpm) at 50 °C. Employing the
Cycloaddition of Bis-enones
aforementioned conditions, bis-enones 1a and 2a were converted
to the corresponding [2 + 2] cycloadducts 1b and 2b in 72%
and 69% yields, respectively, with substantial inhibition of the
Michael cycloreduction pathway. Significantly, cycloadducts 1b
and 2b were obtained as single stereoisomers. The structure of
1b was corroborated via X-ray diffraction analysis of a single
crystal (Table 1).
Tae-Gon Baik, Ana Liza Luis, Long-Cheng Wang, and
Michael J. Krische*
UniVersity of Texas at Austin
Department of Chemistry and Biochemistry
Austin, Texas 78712
ReceiVed March 28, 2001
Table 1. Partitioning [2 + 2] Cycloaddition vs Michael
Cycloreduction Manifoldsa
While photochemically promoted intramolecular alkene [2 +
] cycloadditions are routinely used in the synthesis of complex
2
1
molecular architectures, related metal-catalyzed [2 + 2] cycload-
ditions of tethered alkenes have not been described.2 To date,
metal-catalyzed alkene [2 + 2] cycloadditions have been restricted
to the intermolecular reaction of strained alkene (norbornadienes
or methylenecyclopropanes) and electron-deficient alkene partners,
,3
4
typically using zero-valent nickel catalysts. More recently, chiral
Lewis acids have been shown to catalyze the enantioselective
intermolecular [2 + 2] cycloaddition between electron deficient
alkenes and vinylsulfides or thioketene acetals.2 In this account,
we present the first intramolecular metal-catalyzed [2 + 2]
cycloaddition of alkenes. This methodology allows for the facile
construction of substituted bicyclo[3.2.0] ring systems in diaste-
reomerically pure form.
c
a
See Table 2 for experimental details.
Using these optimized conditions, the cycloaddition of a variety
of bis-enones was explored (Table 2). The capacity of the catalyst
to tolerate functionality in the tether connecting bis-enones was
first examined. Substrates that embody heteroatom-containing
linkages, as in oxygen- and nitrogen-bearing bis-enones 2a and
3a, smoothly underwent [2 + 2] cycloaddition (Table 2, entries
2 and 3). Tethered bis-enones bearing geminal substitution, as in
4a, gave increased amounts of Michael cycloreduction (Table 2,
entry 4). Substrate-directed diastereoselectivity was probed
through the reaction of siloxy-substituted bis-enone 5a (Table 2,
entry 5). The corresponding cycloadduct 5b was obtained as a
single stereoisomer. The siloxy substituent was found to reside
on the concave face of the bicyclo[2.3.0] ring system. The
stereochemical assignment of 5b was verified via X-ray diffraction
of a single crystal. A general model to account for the observed
stereochemistry of all cycloadducts, including 5b, is indicated
below.
Diastereoselective (diketonato)metal-catalyzed aldol and Michael
cycloreductions recently were reported from our labs. In the
course of optimizing the Michael cycloreduction of bis-enones
a and 2a, the following observations were made. Whereas
5
1
Michael cycloreduction represents the exclusive reaction pathway
when 2.4 equiv of phenylsilane are used, reactions conducted in
the presence of 1.2 equiv of phenylsilane gave comparable
amounts of cycloreduction and, remarkably, [2 + 2] cycloaddition
products. Attempts were made to optimize the [2 + 2] cycload-
dition manifold. Further decreasing the amount of phenylsilane
did not substantially alter the product ratio and resulted in
diminished yields of both products. In the absence of silane, no
reaction was observed. Alternative silane sources were screened
for their capacity to induce selection of the [2 + 2] cycloaddition
pathway. Optimal yields of the [2 + 2] cycloadducts 1b and 2b
were obtained with 4.0 equiv of phenylmethylsilane in the
(
1) For selected reviews, see: (a) Bach, T. Synthesis 1998, 683. (b) Winkler,
J. D.; Bowen, C. M.; Liotta, F. Chem. ReV. 1995, 95, 2003. (c) Crimmins, M.
T. Chem. ReV. 1988, 88, 1453. (d) Demuth, M. Pure Appl. Chem. 1986, 58,
1
233. (e) De Keukeleire, D.; He, S.-L. Chem. ReV. 1993, 93, 359.
(
2) For selected reviews on metal-catalyzed cycloadditions, see: (a)
Dzheimilev, U. M.; Khusnutdinov, R. I.; Tolstikov, G. A. J. Organomet. Chem.
Mixed bis-enones containing aliphatic and aromatic enone
partners participate in the cycloaddition. Mixed bis-enone 6a
contains a methyl ketone and provides the corresponding cy-
cloadduct 6b in moderate yield. Finally, heteroaromatic bis-enones
7a-9a, which contain 2-furyl and 3-indolyl residues, also
participate in the cycloaddition reaction.
1
4
991, 409, 15. (b) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96,
9. (c) Hayashi, Y.; Narasaka, K. In ComprehensiVe Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Heidelberg,
1
999; Vol. III, Chapter 33.3, p 1255.
(
3) [2 + 2] Cycloadducts are postulated as intermediates in the catalytic
metathesis of 1,6-enynes: Trost, B. M.; Yanai, M.; Hoogsteen, K. J. Am.
Chem. Soc. 1993, 115, 5295.
The stereochemical outcome of the cycloaddition is independent
of alkene geometry. Both 1a and iso-1a provide equivalent
amounts of 1b as a single stereoisomer. While π-facial intercon-
version of an intermediate cobalt enolate might account for this
convergent stereochemical outcome, such isomerization should
be slow with respect to five-membered ring formation.
The stereochemistry of the [2 + 2] cycloadducts obtained via
metal-catalyzed cycloaddition does not reflect the thermodynami-
(
4) For selected examples of Ni-catalyzed alkene [2 + 2] cycloaddition,
see: (a) Kiji, J.; Yoshikawa, S.; Sasakawa, E.; Nishimurea, S.; Furukawa, J.
J. Organomet. Chem. 1974, 80, 267. (b) Heimbach, P.; Meyer, R. V.; Wilke,
G.; Liebigs Ann. Chem. 1975, 743. (c) Takaya, H.; Yamakawa, M.; Noyori,
R. Bull. Chem. Soc. Jpn. 1982, 55, 852. (d) Ishii, Y.; Kawahara, M.; Noda,
T.; Ishigaki, H.; Ogawa, M. Bull. Chem. Soc. Jpn. 1983, 56, 2181. (e) Saito,
S.; Hirayama, K.; Kabuto, C.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122,
6
1
0776.
5) Baik, T.-G.; Luis, A. L.; Wang, L.-C.; Krische, M. J. J. Am. Chem.
Soc. 2001, accepted for publication.
(
1
0.1021/ja010800p CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/16/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 27, 2001 6717
Table 2. Cobalt0Catalyzed [2 + 2] Cycloaddition of Tethered
a
Enones
species en route to the proposed metallobicylo[3.3.0] intermediate
may possess anion radical character. Accordingly, we note that
electrochemical reduction of 1a provides cycloadducts 1b and
iso-1b in 32 and 17% yields, respectively.7
,8
Cyclopropyl ketones are often used as diagnostic probes for
SET. Cobalt catalyzed cycloaddition of mixed enone 10a, which
contains a cyclopropyl ketone, provides cycloadduct 10b in 42%
yield. However, the persistence of the cyclopropyl moiety does
not conclusively preclude the anion radical character of reactive
intermediates.9
2
In principle, activation of the precatalyst Co(dpm) should
require a substoichiometric quantity of silane. However, excess
silane is required for complete consumption of starting materials,
suggesting the catalyst participates in the competitive dehydro-
genative coupling of silane.10 Indeed, elemental hydrogen is
evolved throughout the course of these reactions. Interestingly,
mass spectroscopic analysis of Co(dpm)
absence of PhMeSiH revealed, in the former case, an intense
signal at 608(0.72), corresponding to the mass of Co(dpm)
2
in the presence and
2
3
.
1
1
Phosphine complexes of Co(II) readily disproportionate. It is
noteworthy that Co(I), obtained via disproportionation, is iso-
electronic with Ni(0), a known alkene [2 + 2] cycloaddition
catalyst.4
In summary, we have developed a metal-catalyzed [2 + 2]
cycloaddition of tethered enones that affords diastereomerically
pure substituted bicyclo[3.2.0] ring systems. An important aspect
of this methodology resides in the potential to systematically
modify the properties of the catalyst to modulate selectivity and
broaden substrate scope; a prospect lacking for related photo-
chemical [2 + 2] cycloadditions. Further studies on the mecha-
nism of this process and the development of improved second-
generation catalyst systems will be reported in a full account.
a
2
Procedure: Co(dpm) (10 mol %) was added to a solution of
phenylmethylsilane (400 mol %) in dichloroethane (0.45 M with respect
to substrate) at room temperature. After 30 min, the bis-enone was
added as a 0.45 M solution in dichloroethane and the reaction was
allowed to stir at 50 °C until complete.
Acknowledgment is made to the Robert A. Welch Foundation, the
NSF-CAREER program and donors of the Petroleum Research Fund
administered by the ACS for partial support of this research. KOSEF is
acknowledged for generous postdoctoral support of Tae-Gon Baik.
Supporting Information Available: Spectral data for all new
1
13
compounds ( H NMR, C NMR, IR, HRMS); X-ray crystallographic
data for 1b, iso-1b and 5b (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
JA010800P
cally preferred configuration. Exposure of 1b to either Brønstead
or Lewis acid catalysts at 30 °C results in clean conversion to
the corresponding trans-derivative iso-1b, which was characterized
via single-crystal X-ray diffraction.
The observed stereochemistry, along with the requirement of
at least one aromatic enone partner, suggests organometallic
(
7) Electrochemical experiments were carried out in a divided cell in CH
CN solution with LiClO as the electrolyte, using reticulated carbon working
and counter electrodes and a Ag/AgCl reference electrode.
3
-
4
(
8) Anion radical [2 + 2] cycloadditions are uncommon: Jannsen, R. G.;
Motevalli, M.; Utley, J. H. P. Chem. Commun. 1998, 539.
(9) Tanko, J. M.; Drumright, R. E. J. Am. Chem. Soc. 1992, 114, 1844.
(
5120.
(11) Socol, S. M.; Verkade, J. G. Inorg. Chem. 1986, 25, 2658.
10) Rosenberg, L.; Davis, C. W.; Yao, J. J. Am. Chem. Soc. 2001, 123,
(
6) Trost, B. M.; Krische, M. J.; Radinov, R.; Zanoni, G. J. Am. Chem.
Soc. 1996, 118, 6297.