The 1,3-dipolar cycloaddition reactions of (1) and (11) with the azomethine
ylides derived from N-benzylidene α-amino acid
esters (2) proceed with good to high
exo-diastereoselectivity giving the cycloadducts (4) and
(12), respectively. The cycloaddition adducts can be converted to highly
functionalised prolines (14), (15) and (17) in high enantiomeric purities. The
Michael addition adducts of (1) and (11) with the azomethine ylides derived
from the N-(disubstituted methylidene) α-amino
acid esters (18), (19) and (33) allow for a practical synthesis of all four
stereoisomers of 4-benzamidopyroglutamate. The stereochemistry of these
cycloaddition and Michael adducts has been extensively determined by
single-crystal X-ray structural analysis [compounds (4b), (5b,d),
(12b,d), (13e), (15), (20), (21) and (27)]. Lithium-chelated transition
state structures have been proposed to rationalize the stereochemical outcomes
of these reactions.