Unified Asymmetric Hydrogenation Enables Stereocontrolled Total Synthesis of Tacaman Alkaloids
Guodan Lin1, Wen Zhang1,2, Jie Liu1
1Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Abstract:
The subgram-scale total synthesis of the tacaman alkaloids (-)-tacamine, (+)-tacamonine, (+)-17-β-hydroxytacamonine, and (-)-decarbomethoxytacamine is reported. Our approach prominently features a unified, highly enantioselective Ir-catalyzed hydrogenation of Wenkert's enamide analogues. This method enables the construction of a series of cis-fused indoloquinolizidine scaffolds with exceptional reaction efficiency and enantioselectivities, achieving yields of up to 98% and enantiomeric excesses (ee) of up to 99%.
Related Concept Videos
Reduction 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...
Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
Reduction 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...
Radical Substitution: Hydrogenolysis of Alkyl Halides with Tributyltin Hydride
The bonds formed in this reaction are stronger than the bonds broken, making it energetically favorable. The reaction follows a radical chain mechanism similar to radical halogenation reactions,...
Reduction 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.
Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.


