Highly Efficient and Practical Pyrrolidine–Camphor‐Derived Organocatalysts for the Direct α‐Amination of Aldehydes

A series of pyrrolidine–camphor‐derived organocatalysts (1–4) were designed and synthesised. These organocatalysts were used for direct α‐amination of aldehydes with dialkyl azodicarboxylates to give the desired α‐aminated products in high chemical yields (up to 92 %) and with high to excellent levels of stereoselectivity (up to >99 % ee). The reactions proceeded rapidly (within 5 min) with low catalyst loading (5 mol‐%) at ambient temperature. Enantioselective aminations of asymmetric α,α‐disubstituted aldehydes in the catalytic system were studied, with reasonable to high stereoselectivities (up to 75 % ee) being obtained. The utility of this methodology was demonstrated with the synthesis of derivatives of β‐amino‐γ‐butyrolactone and a tetrasubstitutedcyclohexane‐derived amino alcohol with high stereoselectivities. Transition models were proposed for the asymmetric α‐amination reactions; they involve hydrogen‐bond interactions between the nucleophilic enamine formed in situ and the nitrogen source.