New Approaches for the Synthesis of Alkenes

Abstract

Alkenes are an important class of compounds common among biologically active molecules and often used as intermediates in organic synthesis. Many alkenes can exist in two stereoisomeric forms (E and Z), which have different structures and properties. The selective formation of the two isomers is an important synthetic goal that has driven the development of new transformations. Here, we describe the development of three new methods of alkene synthesis. The first is a diastereodivergent approach to styrene synthesis through hydroarylation of terminal alkynes. The reaction conditions for this method can be tuned to give either the Z- or E-styrene in high yields and excellent selectivities. This method relies on the tandem catalysis of a Sonogashira cross coupling followed by alkyne semireduction. The second transformation has enabled the synthesis of isomerically pure Z-alkenes from simple starting materials. Using a new mechanistic approach to hydroalkylation, we developed the silver-catalyzed Z-selective alkene synthesis via reductive cross coupling of alkynes with alkyl boranes. Preliminary mechanistic studies have shown that a 1,2-metallate rearrangement of the silver boronate intermediate is the key to the stereochemical outcome of this reaction. The third method has not yet been fully developed, and builds upon the previous Z-selective hydrolkylation. In this new transformation, the focus is to efficiently couple secondary alkyl boranes with alkynes to generate highly complex, enantioenriched Z-alkenes. Preliminary work for this project is discussed herein, and demonstrates the viability of this reaction.