Trichloromethyl ketones: asymmetric transfer hydrogenation and subsequent Jocic-type reactions with amines

Abstract

Amino-amides are important pharmaceutical building-blocks. The enantioselective reduction of trichloromethyl ketones using ruthenium transfer hydrogenation catalysts is reported. The products react in a range of Jocic-type reactions to give enantiomerically enriched amino-amides.

The Development of Phosphine‐Free "Tethered" Ruthenium(II) Catalysts for the Asymmetric Reduction of Ketones and Imines

“…The reduction of trichloromethyl ketones was reported by Fox et al54 In many cases, the untethered catalysts gave good results; however, the tethered catalysts were very effective in several cases (Figure ).…”

Metal‐Free Decarboxylative Trichlorination of Alkynyl Carboxylic Acids: Synthesis of Trichloromethyl Ketones

“…1,1,1‐Trichloroheptan‐2‐one (20a) : 2‐Octynoic acid ( 19a ) (435 mg, 2.0 mmol) afforded 1,1,1‐trichloroheptan‐2‐one ( 20a ) as a colorless liquid; yield: 105 mg (0.5 mmol, 25%); 1 H NMR (500 MHz, CDCl 3 ): δ =2.97 (t, J =7.3 Hz, 2 H), 1.74 (pent, J =7.4 Hz, 2 H), 1.37–1.20 (m, 4 H), 0.91 (t, J =7.2 Hz, 3 H); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ): δ =190.6, 96.5, 33.9, 31.0, 24.5, 22.3, 13.9; HR‐MS (EI): m / z= 215.9875, calcd. for C 7 H 11 Cl 3 O [M] + : 215.9875.…”

Metal‐Free N–H/C–H Coupling for Efficient Asymmetric Synthesis of Chiral Dihydroquinoxalinones from Readily Available α‐Amino Acids

“…Representative examples are the Ir‐ and Rh‐catalyzed hydrogenations reported by Vidal‐Ferran[4a] and Xu,[4b] respectively. Other approaches such as Rh‐catalyzed asymmetric arylation of aldimines[2c] and the use of Jocie‐type reactions have been reported . Although these methods are promising, the toxicity and cost of the transition metals, as well as the difficulty of obtaining the starting materials may limit their practical use on a large scale.…”