title: Asymmetric catalysis with N-heterocyclic carbenes as non-covalent chiral templates.
abstract: N-heterocyclic carbenes are a class of persistent carbenes stabilized by adjacent heteroatoms that are part of a heterocycle. They play a central role in multiple enzymatic biosynthetic reactions that involve thiamine diphosphate. Inspired by this biocatalysis machinery, N-heterocyclic carbenes have emerged as one of the most versatile classes of organocatalysts for organic reactions. However, the asymmetric synthesis of carbon-carbon bonds through a non-covalent interaction mechanism has not been previously established for chiral carbenes. Here, we report an N-heterocylic carbene-catalysed, highly enantioselective process that uses weak hydrogen bonds to relay asymmetric bias. We find that catalytic amounts of hexafluoroisopropanol are the critical proton shuttle that facilitates hydrogen transfer to provide high-reaction rates and high enantioselectivity. We demonstrate that a successful asymmetric reaction of this type can be accomplished through a rational design that balances the pKa values of the substrate, the carbene precursor and the product.
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China.
authors.forename: Jiean
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
mesh_terms: D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D009930:Organic Chemicals / Q000737:chemistry*; D020005:Propanols / Q000737:chemistry; D011522:Protons; D013237:Stereoisomerism; D006845:Hydrocarbons, Fluorinated
chemical_list: D006571:Heterocyclic Compounds; D008697:Methane; D009930:Organic Chemicals; D020005:Propanols; D011522:Protons; C030011:carbene; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated