Photochemical [2+2] Cycloaddition of Alkynyl Boronates

A photochemical [2+2] cycloaddition of alkynyl boronates and maleimides is reported. The developed protocol provided 35-70 % yield of maleimide-derived cyclobutenyl boronates and demonstrated wide compatibility with various functional groups. The synthetic utility of the prepared building blocks was demonstrated for a range of transformations, including Suzuki cross-coupling, catalytic or metal-hydride reduction, oxidation, and cycloaddition reactions. With aryl-substituted alkynyl boronates, the products of double [2+2] cycloaddition were obtained predominantly. Using the developed protocol, a cyclobutene-derived analogue of Thalidomide was prepared in one step. Mechanistic studies supported the participation of the triplet-excited state maleimides and ground state alkynyl boronates in the key step of the process. A photochemical [2+2] cycloaddition of alkynyl boronates and maleimides is described as a convenient method for the synthesis of polysubstituted borylated cyclobutenes tolerating a wide range of functional groups. Physicochemical and structural properties of the products obtained provide rationale for their application as phthalimide isosteric replacements, for example, in Thalidomide. Mechanistic studies confirm that the [2+2] cycloaddition proceeds through initial excitation of the maleimide component.image