Communications
DOI: 10.1002/anie.200902575
Stereoselective Catalysis
Unusual Allylpalladium Carboxylate Complexes: Identification of the
Resting State of Catalytic Enantioselective Decarboxylative Allylic
Alkylation Reactions of Ketones**
Nathaniel H. Sherden, Douglas C. Behenna, Scott C. Virgil, and Brian M. Stoltz*
We recently developed a series
of catalytic enantioselective
allylic alkylation reactions of
cyclic ketone enolates that pro-
ceed by the decarboxylation of
allyl carbonates and b-ketoest-
ers (Scheme 1).[1] These robust
reactions proceed in a variety of
solvents in the presence of
steric hindrance and a wide
range of functional groups, and
have an unusually high toler-
Scheme 1. Palladium-catalyzed enantioselective decarboxylative allylic alkylation reactions of ketone
enolates. dba=trans,trans-dibenzylideneacetone, TMS=trimethylsilyl.
ance to water.[2] To gain further
experimental insight into this
chemistry, we embarked on a
mechanistic study,[3] which has now resulted in the isolation
and full characterization of complex 1 (Figure 1), the resting
state of a prototypical reaction. We describe herein the
identification of this unusual complex and discuss its potential
implications for palladium-catalyzed decarboxylative asym-
metric alkylation reactions and other related transformations.
Initially, we sought to follow the catalytic reaction of a
standard b-ketoester substrate, (Æ )-2, by 31P NMR spectros-
copy (Figure 2, top). The combination of (S)-tBu-phox (3)
with [Pd2(dba)3] in a 2.6:1 ratio at room temperature for
30 min as specified in our standard alkylation procedure[1] led
to a single new resonance at d = 18.8 ppm along with the
signal for the free ligand 3 at d = À5.95 ppm (Figure 2A). The
addition of b-ketoester (Æ )-2 resulted in the complete
disappearance of the resonance at 18.8 ppm and produced a
[*] N. H. Sherden, Dr. D. C. Behenna, Dr. S. C. Virgil, Prof. B. M. Stoltz
The Arnold and Mabel Beckman Laboratories of Chemical Synthesis
and the Caltech Center for Catalysis and Chemical Synthesis
Division of Chemistry and Chemical Engineering
California Institute of Technology
1200 E. California Boulevard MC 164-30, Pasadena, CA 91125 (USA)
Fax: (+1)626-564-9297
E-mail: stoltz@caltech.edu
Figure 1. X-ray crystal structure of complex 1 (one diastereomer
shown), the resting state of the catalytic cycle. The molecular structure
is shown with 50% probability ellipsoids.
[**] We thank NIH-NIGMS (R01 GM 080269-01), Abbott Laboratories,
Amgen, Merck, Bristol-Myers Squibb, Boehringer Ingelheim, the
Fannie and John Hertz Foundation (predoctoral fellowship to DCB),
the Gordon and Betty Moore Foundation, and Caltech for financial
support. Lawrence Henling and Dr. Michael Day are gratefully
acknowledged for X-ray crystallographic structural determination.
The Bruker KAPPA APEX II X-ray diffractometer was purchased
through an NSF CRIF:MU award to the California Institute of
Technology, CHE-0639094. Prof. J. E. Bercaw, Prof. R. H. Grubbs,
Prof. S. E. Reisman, Prof. W. A. Goddard III, and Dr. J. A. Keith are
acknowledged for helpful discussions. Dr. David Vander Velde and
Dr. Scott Ross are thanked for helpful assistance related to NMR.
long-lived resonance at 30.9 ppm (Figure 2B). As the reaction
to form ketone 4 neared completion, the long-lived inter-
mediate slowly reverted to the initial species with a resonance
at 18.8 ppm (Figure 2C).[4]
We proceeded to isolate and characterize the complex
corresponding to the long-lived resonance at 30.9 ppm and
identified it as 1 (Figure 1). Despite the apparent abundance
of this complex in solution under the catalytic reaction
conditions, 1 proved challenging to isolate owing to its air
sensitivity and thermal instability well below 248C both in
solution and as a solvent-free solid.[5] Interestingly, impure
Supporting information for this article is available on the WWW
6840
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 6840 –6843