Asymmetric Assisted Tandem Catalysis: Hydroamination followed by Asymmetric Friedel–Crafts Reaction from a Single Chiral N,N,N′,N′‐Tetradentate Pyridylmethylamine‐Based Ligand

Abstract

With the rising interest in asymmetric catalysis promoted by earth‐abundant elements, a chiral ligand will undoubtedly be the most valuable unit of the catalyst. The first proof of concept of the use of a multitask chiral ligand in an asymmetric assisted tandem catalysis protocol that successively combines metallo‐ and organocatalytic processes is reported herein. In this protocol, the chiral ligand of the newly designed rare‐earth catalyst of the first reaction is converted into a novel chiral organocatalyst for the second transformation by the simple addition of HCl. The observation of some enantioinduction in the tandem sequence—alkyne hydroamination followed by enantioselective Friedel–Crafts alkylation—confirms the relay of the chiral N,N,N′,N′‐tetradentate ligand and the importance of its pyridylmethylamine scaffold.

N-Containing Ligands as Universal Coordination Environments for Rare-Earth Alkyl and Bis(alkyl) Complexes

“…The interaction of Ln(CH 2 SiMe 3 ) 3 (THF) 2 (Ln = Y, Sc) with an equimolar amount of binaphthylamine with benzyl substituents at the nitrogen atoms in THF at 25 °C gave rise to the corresponding neutral alkyl derivatives (Binam(СH 2 Ph) 2 )LnCH 2 SiMe 3 (THF) 2 (Ln = Y (82), Sc (83)) ( Fig. 3) [57]. Complexes 82 and 83 can be stored in the solid state at -20 °C for several weeks with no evidence of decomposition.…”

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 addition, Hannedouche et al recently developed the asymmetric scandium-catalyzed tandem hydroamination/FriedelÀ Crafts reaction of aniline derivative 165 with ethyl 3,3,3-trifluoropyruvate 166 [93]. The process began with an intramolecular hydroamination to give intermediate 167 which further reacted with ethyl 3,3,3-trifluoropyruvate 166 through a FriedelCrafts alkylation, affording final indole 168.…”