Intramolecular Cycloaddition Reactions of N-Acyl Imines. A Stereoselective Approach to the N-Terminal Amino Acid Component of Nikkomycin B

Diels-Alder cyclizations of N-acyl imines derived from glyoxylates 5 and 8 stereoselectively produced cis-fused bicyclo-1,3-dihydrooxazine γ-lactones 7 and 10, respectively. The cycloaddition failed to yield the corresponding δ-lactone 12 derived from precursor 11. Selective ring cleavages of cycloadduct 2 afforded hydroxy amide 13 and α-amino lactone 14. Efficient application of this methodology to the stereoselective synthesis of the N-terminal amino acid portion 15 of nikkomycin B (16) is described. Diels-Alder precursor 21, readily available in three steps from known allylic chloride 17, was cyclized to the bicyclodihydrooxazine 22. This compound was readily converted to lactone 26.