Semi-Pinacol rearrangements (SPRs) are a class of reactions that have become cornerstone transformations in complex molecule synthesis. Described simply as a process in which a C–C or C–H bond connected to an oxygen-containing carbon atom undergoes a 1,2-migration to a vicinal electrophilic carbon center, SPRs are most easily defined by the nature of the electrophilic activation pathway. While the classical SPR involves activation of a leaving group to expose the required electrophilic carbon, the use of allylic alcohols as substrates has dramatically increased the accessibility of this generic transformation. Notable seminal examples include alkene activation via organocatalytic halogenation and epoxidation, Brønsted acid catalysis, palladium catalysis and asymmetric counterion catalysis. Interestingly, there are no examples that involve a C–C bond formation step as part of the electrophilic alkene activation. Furthermore, the asymmetric introduction of a carbon-based electrophile in SPR would generate synthetically useful ketone scaffolds containing vicinal quaternary and aryl-containing tertiary stereogenic centers, which would be challenging to form by other means.<br/>Our laboratory, and also that of MacMillan, has introduced the use of asymmetric copper-bisoxazoline complexes in combination with diaryliodonium salts to provide convenient access to catalytically generated chiral Cu(III)-aryl intermediates (which are aromatic electrophile equivalents). These would undergo union with nucleophiles such as alkenes, and provides a means for enantioselective arylative cross coupling to a variety of versatile products with high enantioselectivities. Herein, we report a copper-catalyzed enantioselective arylative SPR of allylic alcohols using diaryliodonium salts. Chiral Cu(II)-bisoxazoline catalysts activate an electrophilic alkene arylation, initiating a 1,2-alkyl migration to afford a range of chiral spirocyclic ketones with high yields, diastero- and enantioselectivities.

Enantioselective copper-catalyzed arylation-driven semi-pinacol rearrangement of allylic alcohols with diaryliodonium salts

254th National Meeting (2017)

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