Stille Couplings Catalytic in Tin: Beyond Proof-of-Principle

Abstract

Stille cross-couplings1 often involve the palladium-catalyzed union of vinyl or aryl halides with vinylstannanes to form 1,3dienes. Stille reactions are quite tolerant to a large array of functionality, typically proceed with a conservation of olefin geometry, and are most often regiospecific with regards to the newly formed C-C σ-bond. As such, Stille reactions have proven useful in natural product synthesis,2 the construction of new materials,3 heterocycle preparation,4 carbohydrate chemistry,5 and support of bioorganic research.6 Furthermore, Stille couplings are quite compatible with various new technologies. They behave well in a combinatorial setting,2a,7 are rapidly accelerated under microwave irradiation,8 have proven amenable to reaction in the fluorous phase,8b,9 and offer great potential in the very nonpolar environment of supercritical carbon dioxide.10 Despite such synthetic utility, a historic drawback of the Stille reaction has been its reliance on stoichiometric quantities of toxic, costly, and occasionally unstable organostannanes.11,12 Therefore, we believe a Stille reaction, which is catalytic in tin, would be of considerable benefit.13 The invention of such a catalytic method poses several challenges. Perhaps most fundamental among these is that while many important advances in the development of catalytic versions of tin-mediated reactions have been realized,11,14 most prior efforts have focused on tin reagents such as Bu3SnH, Bu2SnO, (BuCH(Et)CO2)3SnBu, etc. Little attention has been given to the invention of catalytic variants for chemical transformations, where the organotin species is a reactant covalently bonded to the organic molecular material of interest. In short, rendering the Stille reaction catalytic in tin would require an initial molecule of organotin hydride to participate in a chemoselective sequence of in situ vinyltin generation, cross-coupling, and then a final transformation of the organotin halide byproduct back to tin hydride.