Biotinylated Rh(III) Complex in Engineered Streptavidin for Accelerated Asymmetric C-H Activation

By T. Hyster, Livia Knörr, T. Ward, T. Rovis. Science, 2012

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Forced Asymmetry in Cp The cyclopentadienyl (Cp) ligand—a pentagon of carbons—is a common feature in transition metal catalysts, but chiral variants of the structure have rarely been applied to asymmetric reactions. Two studies now demonstrate distinct approaches to rendering a Cp-derived rhodium catalyst enantioselective in a tandem carbon-hydrogen activation-ring closure reaction that couples olefins with benzamides (see the Perspective by Wang and Glorius). Hyster et al. (p. 500) tethered a biotin derivative to the Cp ligand to enable docking in a chiral streptavidin protein cavity, which in turn was engineered to further optimize catalytic performance. Ye and Cramer (p. 504) appended chiral substituents on the Cp framework to bias the rest of the coordination environment around the metal center. Modifying an achiral ligand to dock in a protein renders catalysis by its rhodium complex asymmetric. Enzymes provide an exquisitely tailored chiral environment to foster high catalytic activities and selectivities, but their native structures are optimized for very specific biochemical transformations. Designing a protein to accommodate a non-native transition metal complex can broaden the scope of enzymatic transformations while raising the activity and selectivity of small-molecule catalysis. Here, we report the creation of a bifunctional artificial metalloenzyme in which a glutamic acid or aspartic acid residue engineered into streptavidin acts in concert with a docked biotinylated rhodium(III) complex to enable catalytic asymmetric carbon-hydrogen (C–H) activation. The coupling of benzamides and alkenes to access dihydroisoquinolones proceeds with up to nearly a 100-fold rate acceleration compared with the activity of the isolated rhodium complex and enantiomeric ratios as high as 93:7.

Subfields: Inorganic Chemistry, Organic Chemistry

View Paper: https://www.semanticscholar.org/paper/bc09c58a226efe8d1f892ee59f74391bc381136b

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