Imino Transfer Hydrogenation Reductions

Abstract

This review contains a summary of recent developments in the transfer hydrogenation of C=N bonds, with a particularly focus on reports from within the last 10 years and asymmetric transformations. However, earlier work in the area is also discussed in order to provide context for the more recent results described. I focus strongly on the Ru/TsDPEN class of asymmetric transfer hydrogenation reactions originally reported by Noyori et al., together with examples of their applications, particularly to medically valuable target molecules. The recent developments in the area of highly active imine-reduction catalysts, notably those based on iridium, are also described in some detail. I discuss diastereoselective reduction methods as a route to the synthesis of chiral amines using transfer hydrogenation. The recent development of a methodology for positioning reduction complexes within chiral proteins, permitting the generation of asymmetric reduction products through a directed modification of the protein environment in a controlled manner, is also discussed.

Asymmetric Transfer Hydrogenation of 1‐Aryl‐3,4‐Dihydroisoquinolines Using a Cp*Ir(TsDPEN) Complex

“…Interestingly, APA obtained from a commercial source gave consistently lower reactivity (Table S2, entries 22 and 24). [6][7][8][9]. This shows that the reaction conditions were indeed tailored for the iridium-based 1e′.…”

“…Therefore, orthophosphoric acid was investigated further, including the anhydrous phosphoric acid (APA) [11] prepared by mixing the 85 % H 3 PO 4 with stoichiometric amounts of phosphorus pentoxide (Table S2, entries [16][17][18][19][20][21][22][23][24][25][26][27][28]. Interestingly, APA obtained from a commercial source gave consistently lower reactivity (Table S2, [6][7][8][9]. Interestingly, APA obtained from a commercial source gave consistently lower reactivity (Table S2, [6][7][8][9].…”

“…Among those methods, catalytic asymmetric transfer hydrogenation (ATH) of ketones and imines, pioneered by Noyori et al, [1] is now very well established. [2][3][4][5][6][7][8][9][10] Still, this catalytic system has certain limitations, such as the poor reactivity of 1-aryl-3,4-dihydroisoquinolines (1-Ar-DHIQs) as precursors of the chiral 1aryl-1,2,3,4-tetrahydroisoquinoline (1-Ar-THIQ) motif present in naturally-occurring alkaloids (Cryptostylines) and drugs (e.g., Solifenacin [11] or Gantacurium [12] ). Efficient asymmetric hydrogenation protocols for 1-Ar-DHIQs have been reported anhydrous phosphoric acid as an inexpensive additive.…”

Primary trifluoroborate-iminiums enable facile access to chiral α-aminoboronic acids via Ru-catalyzed asymmetric hydrogenation and simple hydrolysis of the trifluoroborate moiety

“…(89 : 11, Table 1 , entry 10). Gratifyingly, Wills's tethered catalyst [( R , R )-TethTsDpen-RuCl] 41 provided full conversion and an excellent 97 : 3 e.r. ( Table 1 , entry 11).…”

Enantioselective Access to Axial Biaryls via Ruthenium‐Catalyzed Hydrogen‐Transfer Reductive Amination

“…After that, the groups of MacMillan, List, Xiao and Zhang have paid their considerable attention to the asymmetric version of reduction amination . To circumvent hazardous hydrogen gas and high pressure apparatus, an alternative strategy to the reduction of the polarized unsaturated C=N bonds was developed, which is so‐called transfer hydrogenation . This strategy is becoming full‐fledged in the reduction of ketones during the past two decades after Noyori developed its efficient Ru/ligand catalytic system .…”