Asymmetric Domino Aza-Michael Addition/[3 + 2] Cycloaddition Reactions as a Versatile Approach to α,β,γ-Triamino Acid Derivatives

Nonproteinogenic
amino acids are prepared by an unprecedented domino
aza-Michael addition-1,3-dipolar cycloaddition, leading to enantiopure
highly substituted pyr­roli­dinopyra­zolines. Nonaflyl
azide serves as highly effective diazo transfer reagent, forming the
link between the conjugate addition and cycloaddition steps. The resulting
pyr­roli­dinopyra­zolines can be rapidly transformed
to either α,β,γ-triamino acids or 3,4-methano-β-prolines.
Peptide coupling can be regioselectively conducted at each of the
amino groups.