Nucleophilic addition to strained rings is an efficient approach for the synthesis of polysubstituted cyclobutanes, which are privileged structural scaffolds in many pharmaceuticals. In this work, we have developed a simple, efficient, transition-metal-free, and scalable route for the synthesis of trisubstituted methylenecyclobutanes via ring opening of bicyclo1.1.0butanes with silyl ketene imines, using B(C 6 F 5 ) 3 as the catalyst under mild reaction conditions. In this fashion, 24 new potential bioisosteres containing trisubstituted methylene cyclobutanes were obtained in good to excellent yields (up to 99% yield). Furthermore, example reactions were performed on a gram scale, and a proposed mechanism is discussed.
Yi et al. (Mon,) studied this question.