Asymmetric Ring Opening/Cyclization/Retro‐Mannich Reaction of Cyclopropyl Ketones with Aryl 1,2‐Diamines for the Synthesis of Benzimidazole Derivatives

Abstract

A highly efficient asymmetric ring-opening/cyclization/retro-Mannich reaction of cyclopropyl ketones with aryl 1,2-diamines has been realized using a chiral N,N'-dioxide/Sc(III) catalyst. Benzimidazoles containing chiral side chains were generated under mild reaction conditions in excellent outcomes (up to 99 % yield and 97 % ee). This method also provides efficient access to chiral benzimidazole-substituted amide and cycloheptene derivatives.

Ring Opening of Donor–Acceptor Cyclopropanes with N-Nucleo­philes

“…In this case, the formation of the pyrrolidine ring was an intermediate stage, whereas, the ultimate products were benzimidazole derivatives 120 (Scheme 59). 115 Therefore, the interactions between ketocyclopropanes and primary amines can involve a more complex pattern than a two-step process, such as the 'nucleophilic small ring opening-1,5-cyclization' sequence. This depends upon the functional groups in the initial molecules and the conditions chosen for the reaction.…”

Recent developments in enantioselective lanthanide-catalyzed transformations

“…To establish that precatalyst 23 was amenable to different RE/M combinations, the asymmetric aza-Michael addition of methylhydroxylamine 31 to chalcones 12 was investigated [20]. Indeed, the use of yttrium complex 32 as precatalyst of the corresponding heterobimetallic Y/Li/BINOL active catalyst at only 3 mol% of catalyst loading in these reactions allowed the corresponding aza-Michael products 33 to be obtained in both excellent yields and enantioselectivities of [88][89][90][91][92][93][94][95][96][97]respectively (Scheme 9).…”

“…In this context, the same reactions were performed in the presence of secondary amine ligand 67 prepared by reduction of ligand 64 by treatment with NaBH 4 . Under these related reaction conditions, the cycloaddition of aryl enones 65 with alkyl enones 29a-c afforded the corresponding cyclobutanes 68 in moderate yields (49-80%), low to moderate diastereoselectivities (20-64% de) albeit with high to excellent enantioselectivities of [84][85][86][87][88][89][90][91][92][93][94][95][96][97]. Notably, using ligand 67 instead of ligand 64 allowed a complementary diastereoselectivity.…”

“…Catalyst 85, generated through self-assembly performed in the presence of MWNT, gave the optimal result in comparison with that was self-assembled before adding MWNT. When 1 mol% of catalyst 85 was used to promote the Henry reaction of aldehydes 77h-l with nitroalkanes 9a-c, it led to the corresponding products 86a-g as major antidiastereomers in moderate to quantitative yields (52-99%), good to excellent anti/syn ratios of 83:17 to >98:2, and uniformly high enantioselectivities of [87][88][89][90][91][92][93][94][95][96][97][98][99]. This reusable confined catalyst exhibited higher catalytic efficiency that the corresponding unconfined catalyst.…”

“…In 2016, Liu and Feng described the first asymmetric route to these products based on an enantioselective scandium-catalyzed domino ring-opening/cyclization/retroMannich reaction of cyclopropyl ketones 159 with aryl 1,2-diamines 160 [92]. As shown in Scheme 51, the process began with the ring-opening of the cycloprane substrate 159 by the diamine 160 to give the corresponding ring-opened intermediate 161 which subsequently underwent cyclization to form tricyclic intermediate 162.…”