Allenes From Alkenes · Catalytic Cross-Coupling/Elimination for Alkene-to-Allene Conversion

Allenes are important to investigations in method development, drug discovery, and design of functional materials. While allenes are generated from alkynes, a method that makes it possible to convert alkenes, which are more abundant and less costly than alkyne, to allenes would be of considerable value. However, such methods are rare and those available require relatively forcing conditions and are not catalytic, limiting the applicability in complex molecule synthesis. Inspired by an unexpected recent discovery by the host group, we will develop a catalytic cross-coupling/elimination (CCE) method that will allow for efficient conversion of alkenes to 1,3-disubstituted allenes. The requisite substrates will be accessed either from olefins via cross-metathesis or from boronic acids/esters via cross-coupling. Cross-coupling will involve readily accessible alkenyl boronates are organohalides and cross-metathesis will be promoted by a Ru, or Mo catalysts, most originally developed by the host group. Our investigations will be guided by specific mechanistic attributes of CCE, as identified through preliminary DFT studies. The utility of catalytic CCE will be demonstrated in two ways: by efficient synthesis of bioactive allenes and through late-stage conversion of anti-cancer natural product epothilone C to its corresponding allenyl variants. These latter compounds highlight the fact that allenes represent a stable form of a twisted alkene (neither E or Z). We will show that through CCE uniquely shaped macrocyclic analogs can be obtained and utilized in lead discovery. The present investigations set the stage for eventual development of a catalytic enantioselective version of CCE.