Silylene transfer to alpha-keto esters and application to the synthesis of gamma-lactones.

Disubstituted alpha-hydroxy acids have been synthesized by metal-catalyzed silylene transfer to alpha-keto esters. A range of substituents are tolerated in the transformation with the exception of branched groups at the vinylic position. The alpha-hydroxy acid products can be converted into gamma-lactones using a variety of lactonization conditions.

Synthesis of tertiary alpha-hydroxy acids by silylene transfer to alpha-keto esters.

Alpha-keto esters can be converted into alpha-hydroxy acids in a single flask involving metal-catalyzed silylene transfer, 6pi-electrocyclization, Ireland-Claisen rearrangement, and hydrolysis. This reaction sequence is stereoselective and tolerates alkyl- and aryl-substituted alpha-keto ester substrates as well as an alpha-imino ester.

Exploring biochemistry and cellular biology with protein libraries.

Polypeptide libraries cast a broad net for defining enzyme and binding protein specificities. In addition to uncovering rules for molecular recognition, the binding preferences and functional group tolerances from such libraries can reveal mechanisms underlying biochemical and cellular processes. Ligands obtained from protein libraries can also provide pharmaceutical lead compounds and even reagents to further explore cell biology.