Diastereoselektive Alkylierung von 3‐Aminobutansäure in der 2‐Stellung

Diastereoselective Alkylation 3‐Aminobutanoic Acid in the 2‐Position The 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 rac 3 , 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.