A transition metal-free regioselective aza-Michael strategy for spiro-heterocycles through a formal [3 + 2]/[4 + 2] spiro-annulation of haloamines

Abstract

Given the prevalence of nitrogen-containing spiro-heterocycles in medicinal chemistry, efficient strategies for forming C–N bonds are still crucial. We describe a transition-metal-free, regioselective aza-Michael formal [3 + 2]/[4 + 2] spiro-annulation of Michael acceptors with haloamines under mild conditions, which provides a broad substrate scope and functional group compatibility, good to excellent yields, straightforward operational procedures, step economy, and excellent regioselectivity while avoiding metal-related toxicity. Its practicality is demonstrated by successful gram-scale synthesis and post-functionalization.