Nucleophilic substitution reactions are among the most fundamental transformations in organic chemistry, widely utilized across synthetic applications. Typically, these reactions occur at primary, secondary, or tertiary carbon stereocenters possessing a leaving group. What about nucleophilic substitution at a quaternary carbon stereocenter with C-C bond cleavage? The idea of nucleophilic displacement at a quaternary stereocenter has remained largely unexplored, primarily due to the high energy required to cleave a C-C single bond. Yet, could nucleophilic substitution at a quaternary center be feasible? Might we achieve a selective C-C bond cleavage with pure inversion or retention of configuration, at will, in cyclic and acyclic systems? This transformation could potentially become a new tool in stereoselective synthesis, allowing for the preparation of regio-, diastereo-, and even enantiomerically enriched products with multiple adjacent stereocenters-despite the inherent stability of the C-C bond as one of the least reactive functional groups in chemistry. The question then arises: how could such a C-C bond cleavage be achieved under conditions mild enough to tolerate more sensitive functional groups, such as C-O or C-X bonds? Ultimately, my research seeks to transform our understanding of nucleophilic substitution at quaternary stereocenters, offering potential new avenues in stereoselective synthesis by enabling controlled C–C bond cleavage under mild conditions to access complex, stereochemically rich products.
References:
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Patel, K.; Lanke, V.; Marek, I. J. Am. Chem. Soc. 2022, 144, 7066-7071.
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