Access to Syn α-Amino-β-Hydroxyesters by N-H Insertion on O-Protected α-Diazo-β-Hydroxyesters

The N-H insertion reaction is a versatile method for creating C-N bonds under mild conditions, providing in particular an efficient access to both natural and non-natural alpha-amino acid derivatives. In this field, the direct N-H insertion on alpha-diazo-beta-hydroxyesters has not yet been investigated and constitutes a significant challenge, due to competitive migration processes. We report herein the first N-H insertions on O-protected alpha-diazo-beta-aryl-beta-hydroxyesters, enabling to synthesize a wide range of alpha-amino-beta-hydroxyesters by tuning the nature of the amine and the aryl substituent. Overall, 28 N-H insertion products have been isolated, with moderate to good yields in most cases, and diastereoisomeric ratios up to 8.0 : 1 in favor of the syn diastereoisomer.