J . Org. Chem. 1996, 61, 6751-6752
6751
Sch em e 1. P r op osed Ca ta lytic Cycle for
Bu 3Sn H-Ca ta lyzed Con ju ga te Red u ction of En on es
Or ga n otin Hyd r id e-Ca ta lyzed Con ju ga te
Red u ction of r,â-Un sa tu r a ted Keton es
David S. Hays, Matthias Scholl, and Gregory C. Fu*
Department of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139
Received May 7, 1996
successful application of this approach to the radical-
mediated conjugate reduction of R,â-unsaturated ke-
tones.12
The 1,4-addition of Bu3SnH to an enone via a radical
chain process (eq 1) was first reported by Pereyre and
Valade in 1965.13-15 Two years later, the same group
noted that a tin enolate can react with a silicon hydride
to generate a tin hydride and a silyl enol ether.16 We
Organotin reagents have become standard tools in
organic synthesis,1 with applications of radical processes
mediated by Bu3SnH being particularly widespread.2,3
One drawback associated with the use of Bu3SnH is the
toxicity of certain triorganotin species,4 and the develop-
ment of non-tin-based alternatives has therefore been the
focus of considerable attention. The pioneering studies
of Chatgilialoglu and Barton have established that tris-
(trimethylsilyl)silane5 and dimethyl phosphite6 may serve
as useful substitutes for Bu3SnH in many synthetic
applications. However, silicon, phosphorus, and tin
radicals are distinct chemical entities, and they can
therefore display disparate behavior, both in terms of
reactivity toward a given functional group7 and in terms
of stereoselectivity.8
Rather than seeking substitutes for organotin reagents,
we are developing tin-catalyzed variants of processes that
are known to be accomplished by a stoichiometric quan-
tity of an organotin compound.9 In one version of this
approach the tin catalyst effects the key transformation
of the substrate, and then an otherwise inert organosili-
con species regenerates the tin catalyst from the initial
reaction product.10,11 This strategy allows us to exploit
the relatively well-understood, sometimes unique, chem-
istry of tin, while greatly reducing the amount of orga-
notin reagent that is required. We describe herein the
have established that these two observations form the
basis for a new catalytic process, the Bu3SnH-catalyzed,
PhSiH3-mediated conjugate reduction of an R,â-unsatur-
ated ketone (Scheme 117 ). Treatment of a wide array of
enones with 10 mol % of Bu3SnH and 1.2 equiv of
PhSiH3 in refluxing toluene (di-tert-butyl peroxide as
initiator), followed by basic hydrolysis, provides the
saturated ketones in good yields (eq 2; Table 1). Hin-
18
(1) Pereyre, M.; Quintard, J .-P.; Rahm, A. Tin in Organic Synthesis;
Butterworths: Boston, 1987.
(2) For reviews of the chemistry of Bu3SnH, see: (a) Neumann, W.
P. Synthesis 1987, 665-683. (b) RajanBabu, T. V. In Encyclopedia of
Reagents for Organic Synthesis; Paquette, L. A., Ed.; Wiley: New York,
1995.
(3) For leading references to radical chemistry, see: (a) Hart, D. J .
Science 1984, 223, 883-887. (b) Giese, B. Radicals in Organic
Synthesis: Formation of Carbon-Carbon Bonds; Pergamon: New
York, 1986. (c) Curran, D. P. Synthesis 1988, 417-439, 489-513. (d)
Regitz, M.; Giese, B. Houben-Weyl, Methoden der Organischen Chemie;
Georg Thieme Verlag: Stuttgart, 1989. (e) Motherwell, W. B.; Crich,
D. Free Radical Chain Reactions in Organic Synthesis; Academic: New
York, 1992. (f) Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry
of Radical Reactions; VCH: New York, 1996.
dered â,â-disubstituted enones are cleanly reduced (Table
1, entries 3 and 4), and dienones undergo selective
monoaddition (Table 1, entries 5 and 619). Control
experiments for each substrate establish that little (0-
(12) For other methods for effecting the conjugate reduction of
enones, see: (a) Larock, R. C. Comprehensive Organic Transformations;
VCH: New York, 1989; pp 9-12. (b) Parkes, K. E. B.; Richardson, S.
K. In Comprehensive Organic Functional Group Transformations;
Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.; Pergamon: New
York, 1995; Vol. 3, pp 127-128. (c) Keinan, E.; Greenspoon, N. In
Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon: New
York, 1991; Vol. 8, Chapter 3.5.
(13) (a) Pereyre, M.; Valade, J . Compt. Rend. 1965, 260, 581-584.
(b) Pereyre, M.; Valade, J . Bull. Soc. Chim. Fr. 1967, 1928-1936. For
an overview, see ref 1.
(14) For an application of this process in natural products chemistry,
see: Laurent, H.; Esperling, P.; Baude, G. Liebigs Ann. Chem. 1983,
1996-1999.
(4) Boyer, I. J . Toxicology 1989, 55, 253-298.
(5) (a) Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188-194. (b)
Giese, B.; Dickhaut, J . In Encyclopedia of Reagents for Organic
Synthesis; Paquette, L. A., Ed.; Wiley: New York, 1995.
(6) Barton, D. H. R.; J ang, D. O.; J aszberenyi, J . C. J . Org. Chem.
1993, 58, 6838-6842.
(7) For example, see: Ballestri, M.; Chatgilialoglu, C.; Lucarini, M.;
Pedulli, G. F. J . Org. Chem. 1992, 57, 948-952. See also ref 5a.
(8) For example, see: (a) Apeloig, Y.; Nakash, M. J . Am. Chem. Soc.
1994, 116, 10781-10782. (b) Lee, E.; Park, C. M.; Yun, J . S. J . Am.
Chem. Soc. 1995, 117, 8017-8018.
(9) For seminal work on Bu3SnH-catalyzed radical processes, see:
(a) Corey, E. J .; Suggs, J . W. J . Org. Chem. 1975, 40, 2554-2555. (b)
Stork, G.; Sher, P. M. J . Am. Chem. Soc. 1986, 108, 303-304.
(10) For applications of this approach to polar chemistry, see: (a)
Tin hydride: Lipowitz, J .; Bowman, S. A. J . Org. Chem. 1973, 38, 162-
165. Vedejs, E.; Duncan, S. M.; Haight, A. R. J . Org. Chem. 1993, 58,
3046-3050. (b) Tin cyanide: Scholl, M.; Fu, G. C. J . Org. Chem. 1994,
59, 7178-7179. Scholl, M.; Lim, C.-K.; Fu, G. C. J . Org. Chem. 1995,
60, 6229-6231.
(11) (a) For a suggestion that radical-mediated reactions might be
susceptible to this strategy, see: Lipowitz, J .; Bowman, S. A. Aldrichim.
Acta 1973, 6, 1-6. (b) For an application of this approach to radical
chemistry, see: Hays, D. S.; Fu, G. C. J . Org. Chem. 1996, 61, 4-5.
(15) Tin enolates exist as a mixture of interconverting tautomers
in which the tin is bound either to oxygen or to carbon. For simplicity,
we have illustrated the oxygen-bound tautomer in eq 1 and Scheme 1.
See: (a) Pereyre, M.; Bellegarde, B.; Mendelsohn, J .; Valade, J . J .
Organomet. Chem. 1968, 11, 97-110. (b) Lutsenko, I. F.; Baukov, Y.
I.; Belavin, I. Y. J . Organomet. Chem. 1970, 24, 359-369.
(16) (a) Bellegarde, B.; Pereyre, M.; Valade, J . Bull. Soc. Chim. Fr.
1967, 746-747. (b) Bellegarde, B.; Pereyre, M.; Valade, J . Bull. Soc.
Chim. Fr. 1967, 3082-3083.
(17) A mixture of silyl enol ethers (bearing zero to two hydrogens
on silicon) is probably formed.
(18) Lower yields are observed when polymethylhydrosiloxane is
employed as the stoichiometric reductant.
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