Diametric Stereocontrol in Dynamic Catalytic Reduction of Racemic Acyl Phosphonates: Divergence from α-Keto Ester Congeners

Abstract

An unexpected dichotomy was observed in the Ru-catalyzed asymmetric transfer hydrogenation of acyl phosphonates: reduction proceeded from the opposite face relative to that observed in the analogous reduction of α-keto esters. The first highly selective catalytic hydrogenation of acyl phosphonates was utilized in the dynamic kinetic resolution of α-aryl acyl phosphonates providing β-stereogenic α-hydroxy phosphonic acid derivatives.

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

“…They have developed a robust methodology for the reduction of α-acyl phosphonates ( 133 ) that provides access to α-hydroxyalkylphosphonates ( 134 ) in excellent yield along with very high enantio- and diastereocontrol (Scheme 25a). 145 Another noteworthy accomplishment from Johnson and coworkers is the reduction of β-aryl α-ketoester via DKR followed by cyclization onto a pendent malonate to form lactone products (Scheme 25b). 146 This methodology provides access to highly functionalized γ -butyrolactones ( 136 ) that possess three contiguous stereocenters and, not surprisingly, has found applications in natural product synthesis and is discussed in Section 3.6.4 of this review.…”

Asymmetric Synthesis of anti-β-Amino-α-Hydroxy Esters via Dynamic Kinetic Resolution of β-Amino-α-Keto Esters

“…10 These examples provided the basis of a hypothesis that β-amino-α-hydroxy-esters could be accessed from racemic β-amino-α-keto esters via dynamic kinetic resolution (Scheme 1). Such reactions are well-established for the isomeric α-amino-β-keto esters and in fact comprise prototypical examples of DKR, 11 but extensions to the β-amino-α-keto esters remain limited to enzymatic catalysis.…”

“…Guided by our previous work, 10 we began by screening catalyst complexes 5–7 which arise from diarylethylene diamine monosulfonamide ligands and [RuCl 2 ( p- cymene)] 2 . 17 The use of complex 5 afforded complete anti diastereoselection 18 but moderate enantioselectivity, necessitating a switch to ligands 6 and 7 , both of which bear a terphenyl sulfonamide.…”

Imidazolium ion tethered TsDPENs as efficient ligands for Iridium catalyzed asymmetric transfer hydrogenation of α-keto phosphonates in water

“…Over the past two decades, the ATH of ketones with catalysts of transition metals Ru, Rh, and Ir complexes of chiral ligand TsDPEN (p-toluenesulfonyldiphenylethylenediamine) and their modifications has been studied extensively and achieved great success [8]. Surprisingly, little 3 progress has been achieved for ATH of α-keto phosphonates [9]. This is probably due to the lability of α-keto phosphonates in the presence of some transition metal complexes [10].…”

“…This is probably due to the lability of α-keto phosphonates in the presence of some transition metal complexes [10]. So far, only one example has been reported by Johnson and co-worker, in which the Ru-catalyzed ATH of α-keto phosphonates was described by the use of HCO 2 H/Et 3 N as a hydride source and DMSO as a solvent, giving the desired products α-hydroxy phosphonates with high enantioselectivity [9]. Recently, ATH performed in water has received growing interest due to its potential benefits in terms of being economic, environmentally benign and hazardless in handling compared to organic solvents.…”