Stereoselective synthesis of perillaldehyde-based chiral ?-amino acid derivatives through conjugate addition of lithium amides.

ABSTRACT: The Michael addition of dibenzylamine to (+)-tert-butyl perillate (3) and to (+)-tert-butyl phellandrate (6), derived from (S)-(-)-perillaldehyde (1), resulted in diastereomeric ?-amino esters 7A-D in a moderately stereospecific reaction in a ratio of 76:17:6:1. After separation of the diastereoisomers, the major product, cis isomer 7A, was quantitatively isomerized to the minor component, trans-amino ester 7D. All four isomers were transformed to the corresponding ?-amino acids 10A-D, which are promising building blocks for the synthesis of ?-peptides and 1,3-heterocycles in three steps. The steric effects of the isopropyl group at position 4 and of the ?-methyl substituent of (R)-N-benzyl-N-?-methylbenzylamine on the reactivity were also studied and, upon application of a chiral amine, excellent stereoselectivity of the conjugate addition was observed. Amino ester 11 was obtained as a single product and transformed to the corresponding amino acids 10A and 10D in good yields on the gram scale.

SUBMITTER: Szakonyi Z 

PROVIDER: S-EPMC4273274 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature