Ag-catalyzed diastereo- and enantioselective vinylogous Mannich reactions of alpha-ketoimine esters. Development of a method and investigation of its mechanism.

An efficient diastereo- and enantioselective Ag-catalyzed method for additions of a commercially available siloxyfuran to alpha-ketoimine esters is disclosed. Catalytic transformations require an inexpensive metal salt (AgOAc) and an air stable chiral ligand that is prepared in three steps from commercially available materials in 42% overall yield. Aryl- as well as heterocyclic substituted ketoimines can be used effectively in the Ag-catalyzed process. Additionally, two examples regarding reactions of alkyl-substituted ketoimines are presented. An electronically modified N-aryl group is introduced that is responsible for high reaction efficiency (>98% conversion, 72-95% yields after purification) as well as diastereo- (up to >98:2 dr) and enantioselectivity (up to 97:3 er or 94% ee). The new N-aryl unit is crucial for conversion of the asymmetric vinylogous Mannich (AVM) products to the unprotected amines in high yields. Spectroscopic and X-ray data are among the physical evidence provided that shed light on the identity of the Ag-based chiral catalysts and some of the mechanistic subtleties of this class of enantioselective C-C bond forming processes.

Al-catalyzed enantioselective alkylation of alpha-ketoesters by dialkylzinc reagents. enhancement of enantioselectivity and reactivity by an achiral Lewis base additive.

An Al-catalyzed enantioselective method for additions of Me(2)Zn and Et(2)Zn to alpha-ketoesters bearing aromatic, alkenyl, and alkyl substituents is disclosed. Transformations are promoted in the presence of a readily available amino acid-based ligand and afford the desired products in excellent yields and in up to 95% ee. Investigations described illustrate that the presence of a Lewis basic additive can lead to significant enhancements in efficiency and enantioselectivity. A mechanistic model that provides a rationale for such effects is provided.

A simple and efficient chemoselective method for the catalytic deprotection of acetals and ketals using bismuth triflate.

Bismuth triflate is a highly efficient catalyst (0.1-1 mol %) for the deprotection of acetals and ketals. The procedure is very facile and selective for acetals derived from ketones and conjugated aldehydes. tert-Butyldimethylsilyl ethers are stable to the reaction conditions. The highly catalytic nature of bismuth triflate and the use of a relatively nontoxic solvent system (THF/H(2)O) make this procedure particularly attractive for large-scale synthesis.