Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 37, 1998 9691
Scheme 1
R′-diazo-R,â-unsaturated ketones,9 which are themselves readily
available by silylation of the corresponding diazoketones.10
Among the several classes of carbenoid reagents we have
examined, sulfur ylides11 and diazo compounds have thus far
proved most effective for the desired [4+1] annulation.12 Table
1 delineates the scope of this new route to substituted cyclopen-
tenones. In a typical reaction, addition of 1.05 equiv of
dimethylsulfonium methylide to 1a in 1:1 THF-DMSO at 0-25
°C for 1.5 h gave the desired cyclopentenone 2a in 75% yield
after chromatographic purification. Dimethyloxosulfonium me-
thylide also combines with 1a to produce this cyclopentenone,
though in lower yield (entry 2). Protodesilylation of annulation
product 2a was readily achieved by exposure to methanesulfonic
acid in methanol at 25 °C for 3 h to afford 3,4-dimethylcyclo-
pentenone in 95% yield.
As indicated in Table 1, diazomethane reacts with TAS-
vinylketenes in a similar fashion, as does commercially available
(trimethylsilyl)diazomethane.13 However, all attempts to employ
higher diazoalkanes and substituted TMS-diazomethanes in the
[4+1] annulation have been unsuccessful; in each case no
significant reaction occurred and the TAS-vinylketene was
recovered unchanged. Fortunately, substituted sulfur ylides11,14
are more nucleophilic and do react with TAS-vinylketenes in the
desired fashion, providing access to highly substituted cyclopen-
tenones in good yield (entries 5 and 6). A notable feature of
annulations involving substituted carbenoid reagents is the
exclusive formation of trans-4,5-substituted cyclopentenones
(entries 4, 5, 8, 10, and 11).
lective due to the shielding effect of the bulky trialkylsilyl group
and should result in the formation of the (Z)-enolate 9.8b
Cyclization of this intermediate could produce the five-membered
ring product directly, although the planar structure of the dienolate
system in 9 may not allow it to achieve an arrangement in which
the π electrons are suitably situated for direct backside displace-
ment of the leaving group. An alternative pathway involves
ionization to produce the 2-oxidopentadienylic cation 11, which
can then undergo conrotatory 4π electrocyclic closure15,16 to
generate the cyclopentenone product. A third pathway, proceed-
ing via the cyclopropanone intermediate 10, cannot be excluded,
particularly in view of the finding that diazomethane adds to
(trimethylsilyl)ketene to generate (trimethylsilyl)cyclopropanone
in good yield.17
The stereochemical outcome of the reactions of substituted
sulfur ylides and diazo compounds (entries 4, 5, 10, and 11) is
consistent with a mechanism involving stereospecific conrotatory
electrocyclic ring closure if one assumes that ionization of the
initial dienolate intermediate occurs to generate a 2-oxidopenta-
dienylic cation 11 with the C-1 substituent cis to the oxygen atom
to minimize nonbonded interactions. If a mechanism involving
concerted electrocyclization is indeed operative, then [4+1]
annulations beginning with TAS-vinylketenes with Z-substituted
alkenyl groups should afford cis-4,5-substituted cyclopentenones.
Studies are underway in our laboratory to test this hypothesis
and to demonstrate the utility of the [4+1] annulation strategy in
the total synthesis of cyclopentanoid natural products.
Acknowledgment. Dedicated to Professor Satoru Masamune on the
occasion of his 70th birthday. We thank the National Institutes of Health
(Grant GM 28273) for generous financial support. J.L.L. and D.M.B.
were supported in part as National Science Foundation Predoctoral
Fellows.
Scheme 1 outlines several alternative pathways to account for
the mechanistic course of the [4+1] annulation. Addition of a
carbenoid reagent to the vinylketene should be highly stereose-
(9) Details will be provided in a forthcoming paper. We have previously
described the generation of vinylketenes by photochemical Wolff rearrange-
ment,5b and Maas has reported the preparation of alkyl- and aryl-(TAS)ketenes
using this reaction.10a,b
(10) (a) Maas, G.; Bru¨ckmann, R. J. Org. Chem. 1985, 50, 2802. (b)
Bru¨ckmann, R.; Schneider, K.; Maas, G. Tetrahedron 1989, 45, 5517. (c)
Bru¨ckmann, R.; Maas, G.; Chem. Ber. 1987, 120, 635.
(11) Reviewed in: Trost, B. M.; Melvin, L. S. Sulfur Ylides; Academic
Press: New York, 1975.
(12) Concurrently with our studies, Tidwell has found that diazo compounds
add to silylated bisketenes in a related process to produce cyclopentene-1,3-
diones and 5-methylene-2(5H)-furanones.6b
(13) (a) Seyferth, D.; Dow, A. W.; Menzel, H.; Flood, T. C. J. Am. Chem.
Soc. 1968, 90, 1080. (b) Shioiri, T.; Aoyama, T.; Mori, S. Organic Syntheses;
Wiley: New York, 1993; Collect. Vol. 8, pp 612-615.
(14) Diphenylsulfonium ethylide: Corey, E. J.; Jautelat, M.; Oppolzer, W.
Tetrahedron Lett. 1967, 2325. Diphenylsulfonium isopropylide: Nadeau, R.
G.; Hanzlik, R. P. Methods Enzymol. 1969, 15, 347.
Supporting Information Available: Experimental procedures and
characterization data for all annulation products (10 pages, print/PDF).
See any current masthead page for ordering information and Web access
instructions.
JA982101R
(15) Pentadienyl cation electrocyclic ring closures are involved in the
mechanism of the Nazarov cyclization. For a review, see: Habermas, K. L.;
Denmark, S. E. In Organic Reactions; Paquette, L. A., Ed.; Wiley: New York,
1994; Vol. 45, pp 1-158.
(16) Epoxidation of vinylallenes produces cyclopentenones via electrocy-
clization of 2-oxidopentadienylic cations analogous to 11. See: Kim, S. J.;
Cha, J. K. Tetrahedron Lett. 1988, 29, 5613 and references therein.
(17) Zaitseva, G. S.; Bogdanova, G. S.; Baukov, Y. I.; Lutsenko, I. F. J.
Organomet. Chem. 1976, 121, C1-C22. Zaitseva, G. S.; Bogdanova, G. S.;
Baukov, Y. I.; Lutsenko, I. F. Zh. Obshch. Khim. 1978, 48, 131.