Asymmetric Transfer Hydrogenation of (Hetero)arylketones with Tethered Rh(III)–N-(p-Tolylsulfonyl)-1,2-diphenylethylene-1,2-diamine Complexes: Scope and Limitations

Abstract

A series of new tethered Rh(III)/Cp* complexes containing the N-(p-tolylsulfonyl)-1,2-diphenylethylene-1,2-diamine ligand have been prepared, characterized, and evaluated in the asymmetric transfer hydrogenation (ATH) of a wide range of (hetero)aryl ketones. The reaction was performed under mild conditions with the formic acid/triethylamine (5:2) system as the hydrogen source and provided enantiomerically enriched alcohols with good yields and high to excellent enantioselectivities. Although the nature of the substituents on the phenyl tethering ring did not alter the stereochemical outcome of the reaction, complexes bearing electron-donating groups exhibited a higher catalytic activity than those having electron-withdrawing groups. A scale-up of the ATH of 4-chromanone to the gram scale quantitatively delivered the reduced product with excellent enantioselectivity, demonstrating the potential usefulness of these new complexes.

Carbonyl Reduction and Biomass: A Case Study of Sustainable Catalysis

“…193 In conjunction with a base (such as Et3N) or as sodium formate, formic acid has been widely used as a reducing agent, decomposing into CO2 and H2 under catalytic conditions. 194 It has been particularly useful in prochiral ketone reduction into secondary alcohol, using Ir, 195 Ru, [196][197][198] Rh complexes, 199 or enzymes 200 (Scheme 18A). Furthermore, LA is co-generated with LA 5-HMF acidolysis, 17 giving a strong incentive to use FA to reduce LA.…”

Progress toward the total synthesis of mirabalin isomers

“…To obtain the anti-isomer of fragment B, we turned our attention to the use of asymmetric transfer hydrogenation of 17 in combination with dynamic kinetic resolution. Preliminary screening employing different catalysts Cat I, 41 Cat II, 42 and Cat III 43,44 with HCOOH/Et3N (5:2) as the hydrogen donor demonstrated that faster reaction times as well as better diastereoselectivities in favor of compound anti-23 (dr = 78:22) were obtained with catalyst Cat III. Moreover, the catalytic charge could be decreased from 2 mol% to 0.1 mol% without any loss of stereoselectivity and compound 23 was isolated with a comparable 70% yield.…”

Efficient kinetic resolution in the asymmetric transfer hydrogenation of 3-aryl-indanones: applications to a short synthesis of (+)-indatraline and a formal synthesis of (R)-tolterodine

“…[30][31][32][33][34][35] Indeed, stereoselective ATH of 1-indanones or 2-substituted-1indanones to produce corresponding 1-indanols or 2substituted-1-indanols, which utilize chiral transition metal (Ru, Rh) catalysts and a HCO 2 H/Et 3 N mixture as a hydrogen source, have already been described. [36][37][38] However, no examples have been reported thus far of ATH promoted transformations of 3-aryl-1-indanones to 3-aryl-indanols having stereogenic centers at C-3. This deciency encouraged us to explore the stereochemical outcome of ATH reactions of 3-aryl-indanones using enantioenriched chiral transition metal catalysts and a HCO 2 H/Et 3 N mixture as the hydrogen source.…”