Diversity-oriented synthesis of enantiopure N-protected β,β-dialkylserines

Abstract

A series of enantiomerically pure N-Boc-protected β,β-dialkylserines was synthesized by addition of the appropriate Grignard reagent to N-(Boc)serine methyl ester, followed by TEMPO-catalysed oxidation of the primary alcohol with sodium chlorite and sodium hypochlorite.Key words: amino acid, serine, β,β-dialkylserines, ring-closing metathesis.

Applications of γ,δ-Unsaturated Ketones Synthesized by Copper-Catalyzed Cascade Addition of Vinyl Grignard Reagents to Esters

“…The copper-catalyzed cascade addition of vinyl Grignard reagent to a carboxylate has proven to be an effective alternative for synthesizing homoallylic ketones 2 from a variety of esters. Inspired by the isolation of homoallylic ketone 2j as major side-product from addition of excess vinyl magnesium bromide to methyl N -(Boc)­serinate during studies to synthesize β-hydroxyvaline, , an examination of the literature found that vinyl Grignard reagents react with carboxylic acid derivatives to give α,β-unsaturated ketones contaminated with tertiary alcohol, with the former preferred in sterically hindered cases . Considering that homoallylic ketone 2 was formed by ester attack, collapse of the tetrahedral intermediate with expulsion of methoxide ion, and conjugate addition to the resulting enone (Scheme ), catalysis with copper salts (e.g., Cu­(OAc) 2 , Cu­(OAc) 2 ·H 2 O and CuCN) was examined to enhance 1,4-selectivity, and was found to improve yield significantly on a broad substrate scope (Schemes –) …”