Beckman Center for Chemical Sciences

10550 N. Torrey Pines Road

La Jolla, CA   92037

email | phone: 858.784.8415

Hydrogen Atom Transfer (HAT). Classical hydrofunctionalization of alkenes requires strong Bronsted acids to form fleeting, high-energy carbocations. In contrast, non-canonical reactions of metal hydrides can hydrofunctionalize alkenes through lower-energy carbon-centered radicals. We proposed that Co, Fe and Mn-catalyzed reactions pioneered by Mukaiyama proceed through Halpern’s HAT mechanistic paradigm. We have used our HAT hydrogenation and HAT isomerization to synthesize inaccessible secondary metabolites (drimane, epoxyhumulene-II, α-funebrene, 7,20-diisocyanoadociane). These reactions also have been applied in total syntheses by other groups due to their high chemoselectivity and chemofidelity (see Ref. 10 below). Our group was the first to combine MH HAT catalysis with nickel-catalyzed cross coupling, which circumvents substrate prefunctionalization and expands the possibilities of each catalytic cycle. Recently, we have shown that this dual catalytic strategy for branched-selective alkene functionalization can be expanded beyond nickel to other metals. 

See publications

  1. Iwasaki, K.; Wan, K. K.; Oppedisano, A.; Crossley, S. W. M.; Shenvi R. A. "Simple, Chemoselective Hydrogenation with Thermodynamic Stereocontrol", JACS, 2014, 136, 1300-1303.

  2. Crossley, S. W. M.; Barabé, F.; Shenvi, R. A. "Simple, Chemoselective, Catalytic Olefin Isomerization” JACS, 2014, 136, 16788.

  3. Green, S. A.; Matos, J. L. M.; Yagi, A.; Shenvi, R. A. “Branch-Selective Hydroarylation: Iodoarene-Olefin Cross Coupling” JACS, 2016, 138, 12779. 

  4. Crossley, S.W.M.; Obradors, C.; Martinez, R.M.; Shenvi, R.A. "Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins." Chem. Rev., 2016, 116, 8912-2000.

  5. Crossley, S.W.M.; Martinez, R.M.; Guevera-Zuluaga, S.; Shenvi, R.A. "Synthesis of the Privileged 8-Arylmenthol Class by Radical Arylation of Isopulegol." Org. Lett., 2016, 18, 2620-2623. 

  6. Obradors, C.; Marinez, R.M.; Shenvi, R.A. "Ph(i-PrO)SiH2: An Exceptional Reductant for Metal-Catalyzed Hydrogen Atom Transfers." JACS, 2016, 138, 4962-4971.

  7. Green, S. A.; Vásquez-Céspedes, S.; Shenvi, R. A. "Iron-Nickel Dual-Catalysis: A New Engine for Olefin Functionalization." JACS, 2018, 140, 11317–11324.

  8. Shevick, S. L.; Obradors, C.; Shenvi, R. A. "Mechanistic Interrogation of Co/Ni-Dual Catalyzed Hydroarylation." JACS, 2018,140, 12056–12068.

  9. Matos, J. M.; Vásquez-Céspedes, S.; Gu, J.; Oguma, T.; Shenvi, R. A. “Branch-Selective Addition of Unactivated Olefins into Imines and Aldehydes.” JACS, 2018, 140, 16976–16981.

  10. Green, S. A.; Crossley, S. W. M.; Matos, J. L. M.; Vásquez-Céspedes, S.; Shevick, S.; Shenvi, R. A. "The High Chemofidelity of Metal-Catalyzed Hydrogen Atom Transfer." Acc. Chem. Res. 2018, 51, 2628–2640.