A Stereoconvergent Annulation in the Synthesis of Lysergic Acid

Several of the most efficient syntheses of the ergoline lysergic acid hinge on a Heck annulation strategy for the construction of the target's central ring. When bearing an ester functionality at C8, results from various research groups have indicated that the stereochemistry of the ester may be important to the overall mechanism of the cyclization. In this report, we aim to deconvolute the nature of this cyclization by presenting a series of experiments that suggest the importance of several factors including the catalyst utilized, base stoichiometry, and reaction time. A mechanistic understanding of this unique Heck reaction gives insight toward how stereochemical resolution can be achieved in the maximization of yield and synthetic practicality.