C O M M U N I C A T I O N S
9).11 Mindful of the known catalytic activity of vanadium-oxo
complexes for alkene epoxidations,12 we examined the performance
of the vanadium-catalyzed asymmetric oxidation with regard to
substrates bearing proximal olefins. Notably, both allylic and
homoallylic substrates showed good stereoselectivity in the resolu-
tion event, demonstrating excellent chemoselectivity for alcohol
oxidation over olefin epoxidation (entries 4, 8). Furthermore, alkynyl
substituents allow for the resolution of a propargyl alcohol (entry
5) albeit with decreased selectivity.
A kinetic resolution of R-hydroxy esters bearing multiple
stereocenters can also be conducted using the current asymmetric
oxidation methodology. For example, diastereomeric substrates
(()-2 and (()-4 resolve cleanly under the reaction conditions
providing both the alcohol and the ketone with high enantioselec-
tivity (eqs 2, 3).
liminary mechanistic investigations suggest molecular oxygen in
the reaction manifold functions solely to reoxidize vanadium(IV)
intermediates to the catalytically active vanadium(V) species, and
its presence is not necessary for initial alcohol oxidation. Efforts
are currently underway to provide detailed mechanistic insight into
the catalytic cycle and to expand the scope and synthetic utility of
the asymmetric oxidation.
Acknowledgment. We gratefully acknowledge the University
of California, Berkeley, Merck Research Laboratories, and Eli Lilly
Co. for financial support. The Center for New Directions in Organic
Synthesis is supported by Bristol-Myers Squibb as a Sponsoring
Member and by Novartis Pharma as a Supporting Member.
Supporting Information Available: Experimental procedures and
compound characterization data. This material is available free of charge
References
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(15) A mechanism that proceeds via initial two-electron reduction of V(V) to
V(III), followed by rapid redox reaction with a second equivalent of V(V)
to give two equivalents of V(IV) is most consistent with the observed
spectral and product-distribution data.
In summary, we have developed an efficient asymmetric oxida-
tion reaction catalyzed by vanadium(V) using molecular oxygen
as the stoichiometric oxidant. The ligand architecture allows access
to both enantiomers of a secondary alcohol by choice of ligand
stereoisomer. The mild reaction conditions and chemoselectivity
of the catalyst system provide access to a range of R-hydroxy esters
in high yield and excellent enantioselectivity. Additionally, pre-
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