Domino Synthesis of α,β‐Unsaturated γ‐Lactams by Stereoselective Amination of α‐Tertiary Allylic Alcohols

Tertiary allylic alcohols equipped with a carboxyl group can be smoothly aminated under ambient conditions by a conceptually new and stereoselective protocol under palladium catalysis. The in situ formed Z‐configured γ‐amino acid cyclizes to afford an α,β‐unsaturated γ‐lactam, releasing water as the only byproduct. This practical catalytic transformation highlights the use of a carboxyl group acting as an activating and stereodirecting functional group to provide a wide series of pharma‐relevant building blocks. Various control reactions support the crucial role of the carboxyl group in the substrate to mediate these transformations. One, two, lactam! A domino synthesis of unsaturated γ‐lactams is reported to proceed by a palladium‐catalyzed amination of allylic alcohols. An intramolecular carboxyl group acts as a stereodirecting functional group, enabling the formation of Z‐configured γ‐amino acids and subsequent cyclization to the targeted lactam scaffolds. This procedure is atom‐efficient and mild, and highlights a new way of allylic alcohol activation under ambient conditions.