Catalytic asymmetric carbon–carbon bond formation via allylic alkylations with organolithium compoun

Abstract

Carbon–carbon bond formation is the basis for the biogenesis of nature's essential molecules. Consequently, it lies at the heart of the chemical sciences. Chiral catalysts have been developed for asymmetric C–C bond formation to yield single enantiomers from several organometallic reagents. Remarkably, for extremely reactive organolithium compounds, which are among the most broadly used reagents in chemical synthesis, a general catalytic methodology for enantioselective C–C formation has proven elusive, until now. Here, we report a copper-based chiral catalytic system that allows carbon–carbon bond formation via allylic alkylation with alkyllithium reagents, with extremely high enantioselectivities and able to tolerate several functional groups. We have found that both the solvent used and the structure of the active chiral catalyst are the most critical factors in achieving successful asymmetric catalysis with alkyllithium reagents. The active form of the chiral catalyst has been identified through spectroscopic studies as a diphosphine copper monoalkyl species. Organolithiums are the prototypical nucleophilic reagent, but the direct use of them as nucleophiles in catalytic asymmetric synthesis has been problematic. Long sought after, conditions have now been identified that allow the highly enantioselective catalytic formation of C–C bonds by a direct SN2′ reaction of organolithiums with allylic halides.

Cite this article

Pérez, M., Fañanás-Mastral, M., Bos, P. et al. Catalytic asymmetric carbon–carbon bond formation via allylic alkylations with organolithium compounds. Nature Chem 3, 377–381 (2011). https://doi.org/10.1038/nchem.1009

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