Synthesis of Isomerically Pure (Z)-Alkenes from Terminal Alkynes and Terminal Alkenes: Silver-Catalyzed Hydroalkylation of Alkynes.

Alkenes are an important class of compounds common among biologically active molecules and often are used as intermediates in organic synthesis. Many alkenes exist in two stereoisomeric forms (E and Z), which have different structures and different properties. The selective formation of the two isomers is an important synthetic goal that has long inspired the development of new synthetic methods. However, the efficient synthesis of diastereopure, thermodynamically less stable, Z-alkenes is still challenging. Here, we demonstrate an efficient synthesis of diastereopure Z-alkenes (Z:E > 300:1) through a silver-catalyzed hydroalkylation of terminal alkynes, using alkylboranes as coupling partners. We also describe the exploration of the substrate scope, which reveals the broad functional group compatibility of the new method. Preliminary mechanistic studies suggest that a 1,2-metalate rearrangement of the silver borate intermediate is the key step responsible for the stereochemical outcome of the reaction.

Diastereodivergent Reductive Cross Coupling of Alkynes through Tandem Catalysis: Z- and E-Selective Hydroarylation of Terminal Alkynes.

A diastereodivergent hydroarylation of terminal alkynes is accomplished using tandem catalysis. The hydroarylation allows highly selective synthesis of both E and Z diastereoisomers of aryl alkenes, from the same set of starting materials, using the same combination of palladium and copper catalysts. The selectivity is controlled by simple changes in the stoichiometry of the alcohol additive. The hydroarylation has excellent substrate scope and can be accomplished in the presence of various classes of compounds, including esters, nitriles, alkyl halides, epoxides, carbamates, acetals, ethers, silyl ethers, and thioethers. The Z-selective hydroarylation is accomplished using a new approach based on tandem Sonogashira coupling and catalytic semireduction. The E-selective hydroarylation involves an additional catalytic isomerization of the Z-alkene. Our explorations of the reaction mechanism explain the role of individual reaction components and how the subtle changes in the reaction conditions influence the rates of specific steps of the hydroarylation. Our studies also show that, although the Z- and E-selective hydroarylation reactions are mechanistically closely related, the roles of the palladium and copper catalysts in the two reactions are different.