Highly enantioselective transfer hydrogenation of racemic α-substituted β-keto sulfonamidesviadynamic kinetic resolution

Abstract

Highly enantioselective transfer hydrogenation of β-keto sulfonamides was developed via dynamic kinetic resolution using a chiral Ru(ii) catalyst with an azeotropic solution of HCO2H/Et3N as a hydrogen donor, affording α-substituted β-hydroxyl sulfonamides in good yields with excellent diastereo- and enantioselectivities. This method is featured with mild conditions, easy operation, and a broad substrate scope, which make it possible to find wide applications in the synthesis of natural products and biologically active compounds containing the α-substituted β-hydroxyl sulfonamide core.

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

“…A derivative of the major enantiomer of the cyclohexylcontaining reduction product 11 a was prepared through reaction with (S)-1-phenylethylisocyate and the X-ray crystallographic structure of this product (Figure 5 A) led to the product configuration assignment of S, in agreement with the comparison of the optical rotation to that reported (see the Supporting Information) and also with the reported precedents. [7][8][9][10][11][12][13] The configurations of 11 f, the OPh derivative of 11 f, and of 11 i were also confirmed by optical rotation comparisons with those reported and the other products were assigned by analogy.…”

“…Zuschriften 14372 www.angewandte.de group favours the position in the transition state in which it is distal from the h 6 -arene of the complex (Figure 5 B). [7][8][9][10][11][12][13] The cyclopropyl group is a particularly compatible substituent in substrates for ATH reactions, with reports having been published of applications to natural product synthesis in which ketones adjacent to cyclopropanes are reduced with high ee values. [16] The sense of induction suggests that it is compatible with an interaction with the h 6 -arene, which accords with our results (Figure 6 A).…”

“…[12] Zhang et al reported the reduction of a-sulfonamide ketones with very high ee values and conversion using the three-carbon (3C) tethered catalyst 2. [13] Asymmetric hydrogenation of sulfone-containing acetophenone derivatives has also been reported using other catalysts including Ru/ diphosphine catalysts, and CBS reagents. [14a-d] In reductions with the [(arene)Ru(TsDPEN)Cl] complexes 1-3, where acetophenone derivatives are most commonly studied, the sense of reduction indicates that the sulfone adopts a position in the transition state for ATH [15] in which it is positioned distal from the h 6 -arene ring on the ruthenium hydride, which is the active catalyst form in the reaction (Figures 2 C and E).…”

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

“…Communications group favours the position in the transition state in which it is distal from the h 6 -arene of the complex (Figure 5 B). [7][8][9][10][11][12][13] The cyclopropyl group is a particularly compatible substituent in substrates for ATH reactions, with reports having been published of applications to natural product synthesis in which ketones adjacent to cyclopropanes are reduced with high ee values. [16] The sense of induction suggests that it is compatible with an interaction with the h 6 -arene, which accords with our results (Figure 6 A).…”

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

“…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. Relevant to our present work are 2-Z-1-indanones and -tetralones wherein Z = alkyl, (het)aryl, F, Cl, CO 2 R′, SO 2 Ph, C(O)Ph, SO 2 NHPh, and CH(OH)CF 3 , which furnish predominantly the corresponding enantiomeric cis -configured products under these reaction conditions.…”