Diastereoselective 1,3-Dipolar Cycloadditions and Michael Reactions of Azomethine Ylides to (2R)-3-Benzoyl-4-methylidene-2-phenyloxazolidin-5-one and (2S)-3-Benzoyl-2-t-butyl-4-methylideneoxazolidin-5-one

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.