Asymmetric Hydrogenation of β‐Keto Sulfonamides and β‐Keto Sulfones with a Chiral Cationic Ruthenium Diamine Catalyst

Abstract

Optically active β‐hydroxy sulfonamides and β‐hydroxy sulfones are very important building blocks for the preparation of bioactive compounds and pharmaceuticals. In this work, a highly efficient asymmetric hydrogenation of β‐keto sulfonamides and β‐keto sulfones has been developed using the phosphine‐free chiral ruthenium complex Ru(OTf)(TsDPEN)(η6‐p‐cymene) as the catalyst, to afford the corresponding β‐hydroxy sulfonamides and β‐hydroxy sulfones in high yields with excellent optical purities. In addition, a cascade asymmetric hydrogenation/dynamic kinetic resolution (DKR) of racemic cyclic β‐keto sulfonamides and β‐keto sulfones was also realized using the same catalyst, to give the corresponding chiral cyclic β‐hydroxy sulfonamides and β‐hydroxy sulfones in good yields with excellent enantio‐ and diastereoselectivities.magnified image

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).…”

“…[7] In 2009, Wang et al reported the use of (R,R)-3 for asymmetric hydrogenation (AH) of a-sulfonyl and a-sulfonamidyl ketones (8; Figure 2 D) to the alcohols 9 and the DKR/AH of related cyclic substrates. [8] The majority of examples contained an aryl substituent and gave greater than 90 % ee, although the reduction of EtCOCH 2 SO 2 Ph in 84 % ee [8] /80 % ee [9] and MeCOCH 2 SO 2 Ph in 82 % ee [8] /91 % ee [9] were also reported. [8] Later reports featured a one-pot formation, and then ATH, of sulfone-substituted ketones under aqueous conditions, [9,10] and the application of a silica-supported variant.…”

“…[8] The majority of examples contained an aryl substituent and gave greater than 90 % ee, although the reduction of EtCOCH 2 SO 2 Ph in 84 % ee [8] /80 % ee [9] and MeCOCH 2 SO 2 Ph in 82 % ee [8] /91 % ee [9] were also reported. [8] Later reports featured a one-pot formation, and then ATH, of sulfone-substituted ketones under aqueous conditions, [9,10] and the application of a silica-supported variant. [11] Bhanage and Vyas reported DKR/ATH of cyclic a-sulfone ketones using a proline-derived catalyst.…”

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).…”