C O M M U N I C A T I O N S
energies, DFT functional comparisons. This material is available free
References
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Figure 2. Relevant internal coordinates (Å) and thermodynamic energies
of intermediates and transition states in this study. Some atoms from the
enolate and PHOX ligand are omitted from the figures for clarity.
(6) See Supporting Information. For most substrates, the optimal solvent was
THF (yield ) 96%, ee ) 88% for product (S)-2); however, the reaction
also performed surprisingly well in a variety of nonpolar solvents,
including benzene (yield ) 99%, ee ) 88% for product (S)-2).
(7) We note that substituted allyl fragments typically used as stereochemical
probes for asymmetric allylation reactions are unsuitable for our catalyst
system. See Supporting Information for details.
(8) Mohr, J. T.; Behenna, D. C.; Harned, A. M.; Stoltz, B. M. Angew. Chem.,
Int. Ed. 2005, 44, 6924-6927.
(9) See Supporting Information. Crystallographic data have been deposited
at the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, and copies can
be obtained on request, free of charge, by quoting the publication citation
and the deposition number 245187.
(10) Pd0(PHOX) is believed to form allylated complex 3 with the concomitant
decarboxylation of 1. Thermodynamic values are calculated with respect
to the uncoordinated products (S)-2 + Pd(PHOX). Esolv is the energy
associated with placing a gas-phase molecule in a solvent continuum and
can be added to ∆E values to obtain solvent-phase results. Other
calculation results are in the Supporting Information.
Figure 3. Summary of energy pathway ∆E + Esolv (solvent ) THF) for
the enantioselective Tsuji allylation reaction.
Overall, these results contradict previous asymmetric allylic
alkylation results involving soft enolate nucleophiles, prochiral allyl
fragments, and Pd(PHOX) complexes that have been determined
to proceed through external attack.3c,i,j Indeed, this mechanism ex-
plains how high ee’s can be obtained without prochiral allyl frag-
ments. These computational results constitute strong evidence of
an inner-sphere mechanism in the Tsuji allylation reaction and may
shed greater light on the details of similar inner-sphere processes
already reported in the literature, especially those involving allyl-
allyl type couplings.
Thus far, we have not satisfactorily identified the enantiodeter-
mining step of this reaction. Our current results suggest that a
concerted process forms products directly from 4 to 10, but we
have not ruled out stepwise transition states 5 and 9. Figure 3
summarizes our calculated data.
(11) Calculations are on 82-atom systems with B3LYP hybrid DFT and mixed
basis set geometries (LACVP** on atoms shown in Figure 3 and the MIDI!
basis set on all other atoms). Single-point energies are calculated with
the LACV3P**++ basis set. In addition to electronic energy and
thermodynamic contributions, we considered single-point solvent effects
for THF (probe radius
) 2.527 Å, ꢀ ) 7.52) using the Jaguar
self-consistent Poisson-Boltzmann solver (ref 12) and the LACV3P**
basis set. Computational studies by our group show that this method leads
to sufficiently accurate reaction barrier heights for large organometallic
complexes, including those of palladium (ref 13). Single-point control
calculations were carried out at these geometries with the PBE (ref 14)
pure density functional DFT and the LACV3P**++ basis set, leading to
differences between critical barriers with rms ) 1.2 kcal/mol.
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(17) Calculations on a non-oxy analogue of this mechanism were first presented
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+46.9 in gas phase and +51.9 kcal/mol in solvent. The explanation for
high barriers of C-C reductive couplings from Pd(II) is discussed in ref
19.
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Acknowledgment. We thank K. Tani, A. Harned, J. Enquist,
and N. Sherden for experimental collaboration and discussion, and
M. Day and L. Henling for crystallography assistance. J.A.K. thanks
R. (Smith) Nielsen for discussions. This research was partly funded
by Chevron-Texaco, and the facilities used were funded by grants
from ARO-DURIP, ONR-DURIP, IBM-SUR, Fannie and John
Hertz Foundation (D.C.B.), and Eli Lilly (J.T.M.) with additional
support from NSF (CTS-0608889, WAG) and NIH-NIGMS
(R01GM080269-01, BMS).
Supporting Information Available: Additional discussion of ex-
periments, X-ray crystal and calculated molecular structures, calculated
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