Selection of Chiral Zinc Catalysts for the Kinetic Resolution of Esters via Dynamic Templating

Abstract

Dynamic combinatorial libraries of chiral tetradentate bis-imine zinc(II) complexes have been prepared and screened for (1) their discrimination of enantiomeric picolinate esters and pyridyl phosphonate transition state analogs (TSAs) and (2) their catalytic activity and selectivity for enantioselective methanolysis of racemic picolinate esters. The zinc complexes are in equilibrium with their imine ligands as well as with the aldehyde and amine building blocks that form them, enabling the composition of the library to adapt in response to the introduction of coordinating substrates or TSAs. Binary (L)Zn(OTf)(solv)(+) complexes are generated either individually or in libraries from chiral tartrate-derived diamines (2,3) and a set of N-heterocyclic aldehydes (4-12) and the distribution of complexes established by ESI-MS analysis. Binding studies of the (diimine)Zn(OTf)(2) complex libraries with enantiomeric R- and S-2-pyridyl phosphonate TSA 13 show chiral discrimination via formation of diastereomeric LZn(R/S-13)(+) complexes with low to moderate enatioselectivity ratios, k(R)/k(S) (α), ranging from 0.5 to 5.0; corresponding templating of selected binary complexes with the enantiomeric substrates, PyrCO(2)CH(OH)Ph (1), show negligible chiral recognition. The rate constants for methanolysis of the R- and S-esters, PyrCO(2)CH(OH)Ph (1) catalyzed by several L*Zn(OTf)(2) complexes range in value several fold depending on L and with enantioselectivity ratios, k(R)/k(S) (α), ranging from 0.76 to 2.8.