StereoCPC · Harnessing Non-Classical Carbocations for Stereoselective Synthesis

Stereoselective synthesis is a central aspect of modern organic chemistry, enabling the precise formation of specific stereoisomers in complex molecular architectures. Key to this process are reactive intermediates such as carbenes, radicals, and carbocations. However, achieving complete stereocontrol over non-classical carbocations in the stereoselective synthesis of acyclic molecules remains a formidable challenge.These fascinating carbocations, despite decades of research, exhibit unpredictable reactivity, making the controlled creation of stereocenters particularly difficult. In this proposal, our primary goal is to achieve comprehensive stereocontrol over non-classical carbocations. We plan to accomplish this by first identifying the specific substitution pattern necessary to generate these carbocations as a single isomer. Then, we will focus on precisely controlling their reactivity to form stereodefined adjacent C–X and C–C bonds at distant positions from the initial carbocation, through molecular rearrangement. This approach not only aims to tame the unpredictable nature of non-classical carbocations but also to harness their reactivities to create highly complex and defined acyclic molecular structures. Additionally, we aim to pioneer new strategies for synthesizing polysubstituted cyclobutanes, and strained fused ring system utilizing bismetalated species, an accomplishment that has never been achieved, despite the growing use of these structures as potential bioisosteres. These methods represent a significant advancement in the stereocontrolled synthesis of complex molecules, addressing longstanding challenges in regioselectivity, substitution patterns, and stereochemistry. By harnessing the unique reactivity of strained rings and non-classical carbocations, this research is set to unlock novel pathways to molecular architectures previously deemed unattainable, significantly enriching the synthetic toolbox of organic chemistry.