Asymmetric Transfer Hydrogenation

Asymmetric transfer hydrogenation (ATH) is a highly versatile tool for stereoselective reduction of C=O and C=N prochiral groups. Particularly useful appear the mono-tosylated 1,2-diamines as chirality inductors in the presence of a mixture of formic acid and triethylamine as a hydrogen source. Alternatively, isopropanol with metal hydroxides may be used. The structure of substrates plays very important role. The cyclic endogenous imines usually give highest optical yield of the products.Below, some examples of ATH applications are given:Res 1 Fig 1 ENUsing this protocol we were able to complete the synthesis of several natural products (cryspine A, trypargine) and some heterocycles of pharmacological importance (praziquantel, aptazepine).

Res 1 Fig 2 EN

 

We also found that simple monoterpenes like 1S-(+)-carene and R-(+)-limonene may be used as inexpensive chiral starting materials for the construction of N-tosylated-1,2-diamines that effectively serve as ligands in ATH reactions.

Res 1 Fig 3 EN

Roszkowski P., Wojtasiewicz K., Leniewski A., Maurin J.K., Lis T., Czarnocki Z., “Enantioselective synthesis of 1-substituted tetrahydro-β-carboline derivatives via the asymmetric transfer hydrogenation”, J. Mol. Cat. – A Chemical, 232, 143-149 (2005)

Szawkało J., Zawadzka A., Wojtasiewicz K., Leniewski A., Drabowicz J., Czarnocki Z., “First enantioselective synthesis of antitumor alkaloid (+)-crispine A and determination ot its enantiomeric purity by 1H NMR”, Tetrahedron: Asymmetry, 16, 3619-3621 (2005)

Czarnocki S. J., Wojtasiewicz K., Jóźwiak A. P., Maurin J. K., Czarnocki Z., Drabowicz J. „Enantioselective synthesis of (+)-trypargine and (+)-crispine E” Tetrahedron 64, 3176-3182 (2008)

Roszkowski P., Maurin J.K., Czarnocki Z. „First enantioselective synthesis of Aptazepine” Synthesis 44, 241–246 (2012)

Roszkowski P., Maurin J.K., Czarnocki Z., „Synthesis of new mono-N-tosylated diamine ligands based on (R)-(+)-limonene and their application in asymmetric transfer hydrogenation of ketones and imines” Tetrahedron Asymmetry 24, 11, 643-650 (2013)

Roszkowski P., Malecki P, Maurin J.K., Czarnocki Z., “Novel (+)-3-carene derivatives and their application in asymmetric synthesis” Synthesis 47, 4, 569-574 (2015)

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