Diastereoselective Î±-Alkylation of Chiral Î²-Borylated Esters
Perfetti, Michael Thomas
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The use of boron in the synthesis and development of asymmetric methodologies and various biological and medicinal compounds has increased significantly over the last decade. This thesis reports the development of a novel diastereoselective reaction for the Î±-alkylation of chiral Î²-borylated esters. We propose that standard deprotonation of chiral Î²-borylated esters with lithium diisopropylamide (LDA) leads to the formation of a boron-â ateâ intermediate that upon treatment with an alkylation reagent collapses to provide chiral Î±, Î²-substituted boronic esters with a high degree of diastereoselectivity. This reaction is powerful in that a wide range of chiral Î²-borylated ester substrates can be employed that possess varying degrees of substitution and steric bulk. Results show that the reaction is syn-selective and provides yields of up to 60%, with diastereomeric ratios as high as (9.7:1). Additionally, alkylation products from bulkier tert-butyl esters provide higher DR values compared to those of methyl esters that possess the same Î²-functional groups. Several techniques were utilized to elucidate the mechanism of this reaction including variations of reaction temperature and equivalents of base, and also real-time analysis of the reaction by 11B NMR experiments.
- Masters Theses