Recent Developments in Asymmetric Hydrogenation and Transfer Hydrogenation of Ketones and Imines through Dynamic Kinetic Resolution

Abstract

The transition-metal-catalyzed asymmetric transfer hydrogenation (ATH) and asymmetric hydrogenation (AH) of α-and β-substituted ketone or imine derivatives are efficient methods for accessing chiral alcohols or amines bearing up to three stereogenic centers through a dynamic kinetic resolution (DKR) process. This review provides a summary of recent work in this field, focusing on the development of new catalytic systems and on the extension of these asymmetric reductions to new classes of substrates. Conclusion

Progress toward the total synthesis of mirabalin isomers

“…Synthesis of fragment A Our retrosynthetic analysis was based on known methods for the introduction of the phenyltetrazolyl sulfone moiety by a hydroboration/Mitsunobu/oxidation sequence applied to alkene 2. We therefore envisaged that the aldehyde 3 represented a useful intermediate in the synthesis of the unsaturated compound 2, and aldehyde 3 could be obtained from α-amino β-ketoester 4 after asymmetric hydrogenation [21][22][23] via a dynamic kinetic resolution, [24][25][26] Claisen condensation and asymmetric hydrogenation (Scheme 3). [27][28][29] Our synthesis began with the preparation of the hydrochloride ammonium salt 4 in two steps from methyl acetoacetate 5 after nitrosation followed by hydrogenolysis of the oxime 6 under acidic conditions.…”

“…Purification by flash chromatography (SiO2, CH2Cl2/MeOH: 9/1) afforded anti-B' as a pale yellow oil (59 mg, 66%). Rf (CH2Cl2/MeOH:9/1, ninhydrin, UV) 0.26; 1 H NMR (300 MHz, MeOD)  7.30 (26). To a solution of (R)-Roche ester 25 (200 mg, 1.69 mmol, 1 equiv) in CH2Cl2 (3 mL) was added at 0 o C benzyl trichloroacetimidate (640 mg, 2.54 mmol, 1.5 equiv).…”

Metal-Catalyzed Asymmetric Hydrogenation of C═N Bonds

“…However, despite the earlier developments of asymmetric hydrogenation of alkenes and ketones, including their large scale industrial applications, the imine reduction is significantly less explored. [3][4][5][6][7][8][9][10][11][12][13] Many efficient complexes designed for the reduction of alkenes and ketones performed poorly while compared to the related imines. It might be due to the C=N double bond properties and the impoverishment of the catalytic activity of the metal via possible coordination by the newly generated amine product.…”

trans-Diastereoselective Ru(II)-Catalyzed Asymmetric Transfer Hydrogenation of α-Acetamido Benzocyclic Ketones via Dynamic Kinetic Resolution

“…Asymmetric transformations comprising a dynamic kinetic resolution (DKR) step are practically very attractive since both involved enantiomers of the stereolabile racemic substrate would ideally converge to a diastereo- and enantiomerically pure product. 1,2 In particular, the DKR encountered in transition-metal-catalyzed reduction of ketones, such as in asymmetric transfer hydrogenation (ATH), is a powerful one-pot protocol for “deracemization” of substrates which possess a stereolabile α-carbon by converting them into alcohols having two contiguous stereogenic centers. 2 A large number of these reductions are catalyzed by enantiomerically pure ansa -Ru(II)–[ ent - trans -RSO 2 DPEN-(η 6 -arene)] complexes 3 (Figure 1) in the HCO 2 H/Et 3 N binary mixture, which acts as both the H-source and an adequate “racemization medium” for the intermediate en route to the final product.…”

“…1,2 In particular, the DKR encountered in transition-metal-catalyzed reduction of ketones, such as in asymmetric transfer hydrogenation (ATH), is a powerful one-pot protocol for “deracemization” of substrates which possess a stereolabile α-carbon by converting them into alcohols having two contiguous stereogenic centers. 2 A large number of these reductions are catalyzed by enantiomerically pure ansa -Ru(II)–[ ent - trans -RSO 2 DPEN-(η 6 -arene)] complexes 3 (Figure 1) in the HCO 2 H/Et 3 N binary mixture, which acts as both the H-source and an adequate “racemization medium” for the intermediate en route to the final product. The substrates scope for such DKR–ATH encompasses aryl, 4 perfluoroalkyl, 5 or acetylenic 6 ketones as well as α-substituted benzocyclic ketones.…”