An enantioselective Mannich reaction of 2-(2-nitrophenylsulfenylimino)acetamide is described. Under the optimized conditions using proline, triethylamine, and diarylthiourea additives, the initially formed Mannich adduct undergoes irreversible cyclization to afford cyclic hemiaminal products in 21-58% yield, with diastereomeric ratios ranging from 53:47 to 83:17. Enantioselectivity reaches up to 97% ee. The presence of N-H functionality of the substrate is crucial for this cyclization; in its absence, the Mannich adduct undergoes facile decomposition. Subsequent reduction in this intermediate efficiently furnished the corresponding homoserine derivative.
Inokuma et al. (Tue,) studied this question.