Journal article
Combined experimental and theoretical study of the mechanism and enantioselectivity of palladium-catalyzed intermolecular Heck coupling
Organic Chemistry, Department of Chemistry, Technical University of Denmark1
Department of Chemistry, Technical University of Denmark2
Uppsala University3
Radioecology and Tracer Studies, Radiation Research Division, Risø National Laboratory for Sustainable Energy, Technical University of Denmark4
Radiation Research Division, Risø National Laboratory for Sustainable Energy, Technical University of Denmark5
Risø National Laboratory for Sustainable Energy, Technical University of Denmark6
The asymmetric Heck reaction using P,N-ligands has been studied by a combination of theoretical and experimental methods. The reaction follows Halpern-style selectivity; that is, the major isomer is produced from the least favored form of the pre-insertion intermediate. The initially formed Ph-Pd(P,N) species prefers a geometry with the phenyl trans to N.
However, the alternative form, with Ph trans to P, is much less stable but much more reactive. In the preferred transition state, the phenyl moiety is trans to P, but significant electron density has been transferred to the alkene carbon trans to N. The steric interactions in this transition state fully account for the enantioselectivity observed with the ligands studied.
The calculations also predict relative reactivity and nonlinear mixing effects for the investigated ligands; these predictions are fully validated by experimental testing. Finally, the low conversion observed with some catalysts was found to be caused by inactivation due to weak binding of the ligand to Pd(0).
Adding monodentate PPh3 alleviated the precipitation problem without deteriorating the enantioselectivity and led to one of the most effective catalytic systems to date.
Language: | English |
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Year: | 2008 |
Pages: | 10414-10421 |
ISSN: | 15205126 and 00027863 |
Types: | Journal article |
DOI: | 10.1021/ja802991y |