American Chemical Society
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C2-Symmetric Copper(II) Complexes as Chiral Lewis Acids. Scope and Mechanism of the Catalytic Enantioselective Aldol Additions of Enolsilanes to Pyruvate Esters

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journal contribution
posted on 1999-01-16, 00:00 authored by David A. Evans, Christopher S. Burgey, Marisa C. Kozlowski, Steven W. Tregay
The C2-symmetric (S,S)-tert-butyl-bis(oxazolinyl)Cu(OTf)2 complex (1a) has been shown to catalyze the enantioselective aldol reaction between α-keto esters and silylketene acetals or enolsilanes with enantioselectivities ranging from 93 to 99%. With substituted silylketene acetals, syn reaction diastereoselection ranging from 90:10 to 98:2 and enantioselectivities ranging from 93 to 98% are observed. High levels of carbonyl regioselectivity (98:2), diastereoselectivity (93:7), and enantioselectivity (97% ee) are also observed in the aldol addition to 2,3-pentanedione. In all instances, the aldol adducts are generated in high yield and in excellent enantiomeric excess using as little as 1 mol % of the chiral complex 1a. Mechanistic insight into the pyruvate aldol reaction has also been gained. Silyl crossover experiments demonstrate that the silyl-transfer step is intermolecular. Based upon these results, TMSOTf has been identified as an addend to accelerate these reactions. Furthermore, solvent was shown to have a dramatic impact on the rates of addition and catalyst turnover in the pyruvate aldol reaction. Crystallographic structures and semiempirical calculations provide insight into the mode of asymmetric induction, allowing the construction of a model in which chelation of the pyruvate ester through a square planar Cu(II) complex accounts for the observed sense of asymmetric induction. Two other Cu(II) complexes, [Cu((S,S-i-Pr-pybox)](SbF6)2 and bis(imine) complex 26, have also been evaluated as enantioselective catalysts for the pyruvate aldol reaction; however, the scope of the process with these systems is more limited.