A Highly Diastereoselective Approach to Conformationally Constrained Serine Analogues: Synthesis of an α-Amino-β-hydroxycyclohexenecarboxylic Acid and Derivatives

A diastereospecific synthesis of α-amino-β-hydroxycyclohexenecarboxylic acid ( 7 ) was found starting from 4-chloromethylene-5(4 H )-oxazolone ( 1 ) which reacted with 2,3-dimethylbutadiene in the presence of EtAlCl 2 . The Diels−Alder reaction gave two diastereoisomeric cycloadducts 2 and 3, depending on the configuration of the starting dienophile 1 . Compounds 2a and 3 were transformed into the ester 4 and the oxazoline 6, respectively, by reaction with MeOH and p -TSA. The reaction of 2a and 3 with dimethylamine in ethanol solution gave the corresponding amides 8 and 9, respectively, which were transformed into the bicyclic oxazoline 10 on reaction with Na 2 CO 3 in acetonitrile. On acidic hydrolysis both oxazolines 6 and 10 were transformed into α-amino-β-hydroxycyclohexenecarboxylic acid ( 7 ) that includes the serine skeleton.