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

^‡ These authors contributed equally to this work.

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 Introduction

2 Initial Studies

3 Various Termination Steps

4 Termination with Heteronucleophiles

5 Natural Product Synthesis

6 anti-Carbopalladations Realized by the Lautens Lab

7 Conclusion and Outlook

Key words

palladium - anti-carbopalladation - cascade - domino reaction - mechanistic studies - reaction design - heterocycles - lysergol

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