Coinage Metal Catalyzed Alkylations of Alkynes and Allenes

Abstract

The formation of new C–C σ bonds is a fundamental aspect of organic synthesis. These bond forming reactions are valued, in part, for their ability to bring together fragments and rapidly develop molecular complexity in convergent syntheses. Herein is described three new coinage metal catalyzed C–C σ bond forming reactions. The first is a copper-catalyzed hydroalkylation of allenes. This reaction makes use of an allyl copper intermediate that undergoes an SE2’alkylation with an alkyl triflate. An investigation of the reaction mechanism revealed the viability of both mononuclear copper and dinuclear copper intermediates, including a unique dinuclear copper allyl species. Following this, the development of a photoinduced copper-catalyzed alkylation of terminal alkynes with primary, secondary, or tertiary bridgehead alkyl iodides as electrophiles is discussed. The reaction provides access to challenging dialkyl internal alkynes as well as an alternative to the traditional bimetallic Sonogashira reaction. Like the Sonogashira reaction, it proceeds though a copper acetylide intermediate, but this intermediate is now directly activated by blue light rather than transmetallated to a second transition metal catalyst. Key to the success of the reaction was the suppression of light promoted polymerization of the starting material by using a terpyridine ligand on copper. Finally, an in-depth investigation of a Z-selective hydroalkylation of terminal alkynes is reported. Highly diastereoselective synthesis of these, thermodynamically less stable, Z-alkene diastereomers has been difficult. To address this challenge, a silver catalyzed hydroalkylation of terminal alkynes with alkylboranes as the coupling partner was developed. The new approach employs the stereoelectronic requirements of a 1,2-metallate shift in the intermediary boronate complex to achieve >300:1 Z:E selectivity. The exceptional selectivity and novelty of the approach led to a full investigation of the mechanism. The proposed mechanism proceeds through an isolable silver coordinated boronate complex that then undergoes a diastereodeterming and rate limiting 1,2-metallate shift. The proposed mechanism relies on the results of stoichiometric analysis of many of the elementary steps, kinetic measurements, KIE and competition experiments, X-ray crystallography, and DFT calculations.