Cascades Involving anti-Carbopalladation Steps: From Our Initial Hypothesis to Natural Product Synthesis

Abstract

Our endeavors in the design, realization and application of a formal anti-carbopalladation of alkynes are summarized. Whereas numerous examples of syn-carbopalladation steps embedded in cascade reactions are known, there have been almost no examples of the corresponding anti-carbopalladation steps. From a personal perspective, this account provides insights on the original considerations and hypotheses, and their validation or invalidation by experimental and computational means. This account also aims at clarifying how different ideas have been developed and how novel reaction sequences paving the way to a plethora of different scaffolds have been designed. The reader will recognize the importance of the interplay between elucidating reaction mechanisms and developing novel methodologies. As a result, useful methods to create homo- and heterotetrasubstituted double bonds have been developed. The broad versatility of these methods has been demonstrated by a novel total synthesis of the indole alkaloid (+)-lysergol.1 Introduction2 Initial Studies3 Various Termination Steps4 Termination with Heteronucleophiles5 Natural Product Synthesis6 anti-Carbopalladations Realized by the Lautens Lab7 Conclusion and Outlook