Sulfone Group as a Versatile and Removable Directing Group for Asymmetric Transfer Hydrogenation of Ketones

Abstract

The sulfone functional group has a strong capacity to direct the asymmetric transfer hydrogenation (ATH) of ketones in the presence of [(arene)Ru(TsDPEN)H] complexes by adopting a position distal to the η6‐arene ring. This preference provides a means for the prediction of the sense of asymmetric reduction. The sulfone group also facilitates the formation of a range of reduction substrates, and its ready removal provides a route to enantiomerically enriched alcohols that would otherwise be extremely difficult to prepare by direct ATH of the corresponding ketones.

Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution

“…Asymmetric transformations comprising DKR processes are very attractive since racemic substrates converge ideally to a diastereo- and enantiomerically pure product in this transformation. − In particular, the DKR encountered in asymmetric transfer hydrogenation (ATH) of ketones is a powerful protocol for “deracemization” of substrates, which possess a stereolabile α-carbon by converting them into alcohols with two contiguous stereogenic centers. − In 1989, Noyori and co-workers reported trailblazing work on the asymmetric hydrogenation of β-keto esters using Ru–BINAP catalysts . Since then, the utility of reductive DKR processes has been further accentuated by taking advantage of asymmetric transfer hydrogenation (ATH) with bifunctional Ru, Rh, and Ir catalysts containing chiral N -sulfonyl-1,2-diamine scaffolds. − …”

Ru‐TsDPEN catalysts and derivatives in asymmetric transfer hydrogenation reactions

“…In the year 2020, Vyas et al reported about the functional group capability to control enantioselectivity of alcohols which was synthesized via asymmetric reduction of ketone using Ru-tethered catalyst. 75 Scheme 32, explains involvement of temporary directing group which can control enantioselectivity of synthesized product after the removal of "masked" group. In this text although role of catalyst in controlling enantioselectivity is not as important as the position of sulfone in transition state which is distal to η 6 -arene ring of tethered catalyst.…”

“…47-49 in (61-82) %yield whereas from D (i-iii) and F (iiii), Cat. 50-52 has been produced in (62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79) %yield. Thus, cat.…”

η6‐Arene CH−O Interaction Directed Dynamic Kinetic Resolution – Asymmetric Transfer Hydrogenation (DKR‐ATH) of α‐Keto/enol‐Lactams

“…Wills et al. also disclosed a sulfone‐directed asymmetric transfer hydrogenation to convert simple ketone substrates that could be applied with dynamic kinetic resolution while the substrate scope of this method was relatively narrow and all of them comprised aryl groups [13] …”