title: Rh(I)-bisphosphine-catalyzed asymmetric, intermolecular hydroheteroarylation of α-substituted acrylate derivatives.
abstract: Asymmetric hydroheteroarylation of alkenes represents a convenient entry to elaborated heterocyclic motifs. While chiral acids are known to mediate asymmetric addition of electron-rich heteroarenes to Michael acceptors, very few methods exploit transition metals to catalyze alkylation of heterocycles with olefins via a C-H activation, migratory insertion sequence. Herein, we describe the development of an asymmetric, intermolecular hydroheteroarylation reaction of α-substituted acrylates with benzoxazoles. The reaction provides 2-substitued benzoxazoles in moderate to excellent yields and good to excellent enantioselectivities. Notably, a series of mechanistic studies appears to contradict a pathway involving enantioselective protonation of a Rh(I)-enolate, despite the fact that such a mechanism is invoked almost unanimously in the related addition of aryl boronic acids to methacrylate derivatives. Evidence suggests instead that migratory insertion or beta-hydride elimination is enantiodetermining and that isomerization of a Rh(I)-enolate to a Rh(I)-heterobenzyl species insulates the resultant α-stereocenter from epimerization. A bulky ligand, CTH-(R)-Xylyl-P-Phos, is crucial for reactivity and enantioselectivity, as it likely discourages undesired ligation of benzoxazole substrates or intermediates to on- or off-cycle rhodium complexes and attenuates coordination-promoted product epimerization.
authors.affiliation: Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Filloux
authors.forename: Tomislav
authors.initials: T
authors.lastname: Rovis
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000179:Acrylates; D001583:Benzoxazoles; D009942:Organometallic Compounds; D010720:Phosphines; D012238:Rhodium