Asymmetric Synthesis of Silylated α-Amino Acid Esters through Dynamic Kinetic Resolution

Abstract

Esters of three types of silylated alpha-amino acids have been prepared from appropriate zirconaaziridines. Slow addition (syringe pump) of the (R,R) carbonate of trans-stilbene gave metallacycles with the maximum possible diastereomeric excess (as determined by the diastereomeric excess produced by the Hoffmann test-the same reaction but with racemic carbonate). Methanolysis gave esters (RO(2)C)CH(R')(NHPh) (R' = Me(3)Si, Me(3)SiCH(2), and p-Me(3)SiC(6)H(4)) with the same optical purity at the alpha carbon.

Isolation and Characterization of Well‐Defined Silica‐Supported Azametallacyclopentane: A Key Intermediate in Catalytic Hydroaminoalkylation Reactions

“…Precedent examples for such a reactivity can be found in the works of Buchwald,15 Norton,16 Whitby,17 and Blagg two decades ago 17b,18. Zirconaaaziridines can generate, after work‐up, functionalized amines by reaction with unsaturated CC bonds1b (olefins and acetylenes) and CX bonds1b (aldehydes, carbonates16a,b,e,19 and imines1b). This passes by the formation of a 5‐membered zirconacycle through intermolecular1b or intramolecular20 insertion into the ZrC bond of the metallaaziridine.…”

Chemistry of Silicon‐Containing Amino Acids

“…A second and stereoselective method for a-silyl-a-amino acid synthesis, pathway (3), utilizes the zirconium imine complex 15 and its reaction with an optically active carbonate [14]. The stereochemistry of the carbonate controls formation of the new chiral center of the a-silyl-a-amino acid.…”

Straightforward Synthesis of Chiral Silylated Amino Acids through Hydrosilylation

“…It was surprisingly proposed as a phenylalanine isostere 7. Asymmetric syntheses were reported7–9 and more recently, enzymatic deracemisation10,11 and dynamic kinetic resolution12 were employed to prepare optically active TMS‐Ala. Syntheses of derivatives with various triaryl or alkylarylsilyl groups showed difficulties primarily owing to steric hindrance 13,14…”