Palladium-catalyzed allylic substitution between C-based nucleophiles and 6-azabicyclo[3.1.0]-hex-3-en-2-oxy derivatives: A new selectivity paradigm

The reaction between α-hydroxy-(or α-acetoxy) cyclopenten-aziridines (6-azabicyclo[3.1.0]hex-3-en-2-ols or acetates) and C-based nucleophiles in the presence of Pd(0)-catalysis was investigated. In all the cases studied, the reaction was totally regio- and diastereo-selective, affording a single adduct in moderate to good yields. Specifically, attack of the nucleophile at position 3 of the cyclopentene moiety, anti to the vicinal oxy group, with vinylogous ring opening of the aziridine ring, was observed. When the carbon acid is a very acidic methylene (pKa(DMSO) ≤ 7.3), the resulting adduct is a zwitterion, resulting from an intramolecular proton transfer between the amino group and the carbon acid moiety taking place after the C–C bond formation. A plausible mechanism for this transformation is put forward. [Display omitted]