C O M M U N I C A T I O N S
are focused on exploiting this unique approach to alkene function-
alization by expanding the scope of these processes to other cross-
coupling partners and asymmetric catalysis.
Acknowledgment. This work was supported by the National
Institutes of Health (Grant NIGMS RO1 GM3540). M.S.S. thanks
the Dreyfus Foundation (Teacher-Scholar) and Pfizer for their
support. K.M.G. thanks Sanofi-Aventis for a graduate research
fellowship. We are grateful to Johnson Matthey for the gift of
various Pd salts. We would like to thank Dr. Jim Muller for
assistance with the ESI-MS experiments.
Supporting Information Available: Experimental procedures and
characterization data for substances. This material is available free of
References
Figure 1. Mechanistic experiments.
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To explore the validity of our initial mechanistic hypothesis, two
isotopic labeling experiments were performed to determine the
origin of the proton incorporated into the product (Figure 1A). When
using (CH3)2CHOD as solvent, no deuterium is incorporated into
the product, ruling out the involvement of acidic protons in the
process.14 However, when using (CH3)2CDOH as solvent, 92% of
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(Scheme 1A).5 The production of two isotopomers supports the
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π-benzyl species when using a styrenyl substrate.20 This hypothesis
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intermediate can be similarly stabilized via a possible π-allyl species
(Figure 1B). This reaction proceeds modestly to yield the reductive
coupling product as a single regioisomer and 1:1 mixture of
diastereomers. Unfortunately, simple alkenes such as decene do
not undergo reductive coupling under these conditions.
In conclusion, we have disclosed a fundamentally different
approach to Pd-catalyzed cross-coupling reactions. In this process,
Pd0 is not oxidized by the organic substrate, but the requisite PdII
organometallic species is accessed via a PdII-catalyzed alcohol
oxidation to produce a Pd-hydride followed by alkene insertion.
This contrasting approach allows for the facile and highly regi-
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reactions. It is also important to point out that this reductive coupling
reaction is performed under aerobic conditions wherein the reduction
of O2 is necessary to complete the catalytic cycle. Current efforts
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