Palladium/GF-Phos-catalyzed asymmetric carbenylative amination to access chiral pyrrolidines and piperidines

Abstract

The cross-coupling of N-tosylhydrazones has emerged as a powerful method for the construction of structurally diverse molecules, but the development of catalytic enantioselective version still poses considerable challenge and only...

Recent advances in Pd-catalyzed asymmetric cyclization reactions

“…Recently, in the presence of chiral palladium catalysts ligated by their developed GF-Phos , the asymmetric carbenylative amination between N -tosylhydrazones 791 and ( E )-vinyl iodides 790 which contain an amine moiety through a carbene migratory insertion/Tsuji–Trost sequence that opened a new avenue for the synthesis of a variety of chiral 2-substituted pyrrolidines and piperidines with high chemo-, regio-, enantioselectivities was accomplished by the group of Zhang and Li (Scheme 185). 357 This reaction involved the key intermediate palladium carbene Int-I , which underwent migratory insertion to form the π-allylpalladium intermediate Int-II , followed by the nucleophilic attack by the nitrogen atom, yielding the desired product. The significance of this method was further demonstrated by the rapid asymmetric synthesis of natural product (−)-norruspoline.…”

Sadphos as Adaptive Ligands in Asymmetric Palladium Catalysis

“…In addition to the above-mentioned transformation, this coupling strategy was used for the carbenylative amination of vinyl iodides with N -sulfonylhydrazones (Scheme ). The treatment of ( E )-vinyl iodide-tethered nucleophiles with N -tosylhydrazones can produce an array of optically active 2-substituted pyrrolidines and piperidines in up to 93% yield and 93% ee , using Pd 2 (dba) 3 ·CHCl 3 as the catalyst, GF-Phos ( S , Rs )- GF1 as the ligand, t BuOLi as the base, triethylbenzylammonium chloride (TEBAC) as the solubilizer, and Ag 2 CO 3 as the additive. This process represents a rare example of N -sulfonylhydrazone-based carbenylative insertion, forming an π-allylpalldium intermediate and initiating the subsequent intramolecular amination.…”

Chiral oxalamide phosphine (COAP)-Pd-catalyzed enantioselective cascade formal [4 + 1] annulation for enantioenriched 2,3-disubstituted indolines and further DFT study on regio- and stereocontrol

“…The catalytic results indicate that the steric and electronic properties of the phosphine moiety exert a measure of influence on both reactivity and enantioselectivity of the reaction. After further examining several common organic solvents (entries [16][17][18][19], the optimized reaction conditions were established as follows: the reaction was performed in the presence of 5.0 mol% of Pd 2 (dba) 3 , 12.0 mol% of ligand L11 with the molar ratio of 1a : 2a being 1 : 1.2, Cs 2 CO 3 as the base and BnNEt 3 Cl as the phase transfer reagent in a mixed solvent (DCM : i-PrOH was 10 : 1 (v/v)) at 15 °C (entry 13; see the ESI † for more details).…”

“…13 In terms of the catalytic mechanism, the aryl phosphine unit and the oxalyl amide motif, respectively, serve as strongly and weakly coordinating groups to the catalytic metal for tuning the regio-and stereoselectivity of an asymmetric reaction. 14 With COAP ligands in hand, we speculated whether these types of ligands could be applied to Pd-catalyzed asymmetric cascade biphilic formal [4 + 1] annulation of racemic vinyl benzoxazinones 15 with N-tosylhydrazone sodium salts, 16 which might provide 2,3-disubstituted indolines in good yields with high regio-, diastereo-and enantioselectivity (Scheme 1e).…”