C O M M U N I C A T I O N S
Table 3. Scope of the Allylic CsH Alkylation Reaction
unprotected indole are also well-tolerated (entries 19-20, 23-25). This
functional group tolerance is unexpected given that heteroaromatics
are often reactive with and/or attenuate the electrophilicity of Pd(II)
catalysts.
To demonstrate the synthetic utility of these alkylation products we
investigated further transformations. The nitro moiety can be selectively
reduced by the action of zinc dust to furnish the amine 13 in excellent
yield (eq 2). This product may be classically resolved to furnish
optically enriched unnatural R-amino acid precursors. Alternatively,
taking advantage of the nucleophilicity retained by the methine carbon
of 8, a second alkylation can be effected with trans-ꢀ-nitrostyrene (eq
3). This asymmetric conjugate addition, catalyzed by a modified
cinchona alkaloid 14,8 proceeded in high yield with excellent diastereo-
and enantioselectivities, to afford an optically enriched, structurally
complex R,R-disubstituted amino acid precursor (+)-15.
In summary, the first Pd(II)-catalyzed allylic CsH alkylation is
disclosed, providing a novel method for formation of sp3-sp3 C-C
bonds directly from C-H bonds. We anticipate that this reaction and
others like it that provide direct disconnections for rapidly building
carbon frameworks will play an important role in advancing synthesis.
Further investigations to expand the scope of both substrate and
nucleophile are ongoing.
Acknowledgment. M.C.W. thanks the NSF (CAREER CHE-
0548173) for financial support and Merck, Bristol-Myers Squibb, and
Pfizer for generous gifts. We thank Sigma-Aldrich for a gift of catalyst
1, and S. R. Wilson for X-ray crystallographic analysis. A.J.Y.
gratefully acknowledges an Abbott graduate fellowship. J. H. Delcamp
confirmed entry 24, Table 3.
Supporting Information Available: Experimental procedures, full
characterization, and additional experiments. This material is available
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a Olefin (1 equiv), 5 (3 equiv), DMBQ (1.5 equiv), AcOH (0.5
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yields (50-70%) Via standard column chromatography. We have noted
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carbon (e.g., electron-donating groups increase its stability favoring
branched isomers).7
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Functionalities that are unstable to traditional palladium(0)-catalyzed
allylic alkylations, such as aryl halides and triflates, are inert to these
oxidative conditions (entries 5, 17, 22-23). A variety of pharmacoph-
oric functionalities such as catecol, indanone, benzotriazole, and
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