Biocatalytic, asymmetric radical hydrogenation of unactivated alkenes
Jaicy Vallapurackal1, Rajib Mandal1, Justin Bossenbroek1
1Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.
Abstract:
Alkene hydrogenation is a cornerstone of chemical synthesis, yet enzymatic strategies remain limited to electron-deficient substrates by means of hydride transfer. Using heme enzymes, we unlock a hydrogenation pathway for the asymmetric reduction of unactivated olefins. A silane-promoted heme-cysteine redox cycle in the active site catalyzes sequential hydrogen atom transfer to challenging scaffolds, including 1,1-disubstituted as well as tri- and tetrasubstituted alkenes. The evolved enzymes are promiscuous and oxygen tolerant, use Earth-abundant iron, and can operate on the gram scale under ambient conditions. Orthogonal hydrogen atom sources enable site-divergent asymmetric isotope labeling. Mechanistic and computational studies support a stepwise radical process. Our work introduces a biochemical approach for stereoselective olefin reduction and provides a platform for next-generation biocatalytic hydrogenation.
More Related Videos
06:46Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate
Published on: June 21, 2017
05:34Efficient Synthesis of Polyfunctionalized Benzenes in Water via Persulfate-promoted Benzannulation of α,β-Unsaturated Compounds and Alkynes
Published on: December 16, 2019
Related Concept Videos
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
02:13Reduction of Alkenes: Catalytic Hydrogenation
Metals like palladium, platinum, and nickel are commonly used in their solid forms — fine powder on an inert surface. As these catalysts remain insoluble in the reaction mixture, they are referred to as heterogeneous catalysts.
The hydrogenation process takes place on the...
02:24Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
01:25Radical Anti-Markovnikov Addition to Alkenes: Overview
01:17Radical Anti-Markovnikov Addition to Alkenes: Mechanism
The mechanism starts with chain initiation, which involves two steps. In the first chain initiation step, a weak peroxide bond is homolytically cleaved upon mild heating to form two alkoxy radicals. In the second initiation step, a hydrogen atom is abstracted by the alkoxy...
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.