An intramolecular Pd-catalyzed cascade reaction is presented that consists of a formal anti-carbopalladation of a C-C triple bond followed by C-H activation. As a result, oligocyclic ring systems with an embedded tetrasubstituted double bond are formed. The key to success in affording the trans geometry of the emerging double bond are alkyne units with residues that must not undergo β-hydride elimination (e.g., t-butyl or silyl groups). Silyl groups proved to be a perfect handle to further convert the tetrasubstituted alkenes. The evaluation of kinetic data with a deuterium-labeled compound and X-ray analyses of trapped intermediates provided additional insight into the catalytic cycle.

An intramolecular cascade reaction consisting of a formal anti-carbopalladation terminated by the ringopening of a cyclopropanol unit is presented. The products, which involve tetrasubstituted alkene units embedded in an oligocyclic ring system, are generated in moderate to excellent yield. The opening of the cyclopropanol unit leads to a keto group in the γ-position to the emerging double bond.

An intramolecular Pd-catalyzed trans-dicarbofunctionalization of internal alkynes using aryl bromides and aryl stannanes is presented. Tetrasubstituted double bonds embedded in an oligocyclic ring system are obtained in a regio- and diastereoselective fashion. The transformation features a broad substrate scope and functional-group tolerance.

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

An intramolecular palladium‐catalyzed trans‐carbocarbonation cascade is presented that consists of a formal anti‐carbopalladation of an internal carbon‐carbon triple bond terminated by a Suzuki cross‐coupling reaction. The key to success in obtaining the anti‐geometry of the emerging double bond is the use of alkyne units with substituents that avoid β‐hydride elimination (e. g. tert‐butyl or silyl). The products, involving tetrasubstituted double bonds embedded in a seven‐ or eight‐membered ring system, are formed in moderate to good yields.