Diastereoselektive Alkylierung von 3‐Aminobutansäure in der 2‐Stellung

Abstract

Diastereoselective Alkylation 3‐Aminobutanoic Acid in the 2‐PositionThe enantiomerically pure 3‐aminobutanoic acids (R)‐ and (S)‐6 are readily available by preparative HPLC separation of the two diastereoisomers 5 obtained from addition of (S)‐phenethylamine to methyl crotonate and subsequent hydrogenolysis (Scheme 2). (S)‐Methyl 3‐(benzoylamino) butanoate ((S)‐3) is also available by enzymatic kinetic resolution with pig‐liver esterase. The N‐benzyl‐ and N‐ benzyloxycarbonyl derivatives rac3,8, and 9 of 3‐aminobutanoates are doubly deprotonated with LDA and alkylated or aminated in high selectivity (17 examples, relative topicity like; see Tables 1 and 2). The configuration of three of the products is assigned (Schemes 4–6), and in four cases, the free α‐substituted β‐amino acid is prepared by acidic hydrolysis (see Table 3). It is shown that the doubly lithiated β‐amino‐acid derivative is solubilized, and its reactivity may be strongly influenced by the presence of 3 equiv. of LiCl.