Modular Synthesis of Novel Macrocycles Bearing α,β‐Unsaturated Chemotypes through a Series of One‐Pot, Sequential Protocols

A series of one-pot, sequential protocols was developed for the synthesis of novel macrocycles bearing α,β-unsaturated chemotypes. The method highlights a phosphate tether-mediated approach to establish asymmetry, and consecutive one-pot, sequential processes to access the macrocycles with minimal purification procedures. This library amenable strategy provided diverse macrocycles containing α,β-unsaturated carbon-, sulfur-, or phosphorus-based warheads.