Metal‐Templated Asymmetric Catalysis: (Z)‐1‐Bromo‐1‐Nitrostyrenes as Versatile Substrates for Friedel–Crafts Alkylation of Indoles

Abstract

An asymmetricF riedel-Crafts alkylation of indoles with (Z)-1-bromo-1-nitrostyrenes, which is efficiently catalyzed by an umber of hydrogenb ond interactions with the ligand sphere of bis-cyclometalated iridium complexes, has been reported. The proposed transition state exploits ah ydrogen bond network, which is illustrated by the co-crystal structure of am odel catalyst with an analog of the nitro substrate. The bromof unctional group not only plays an important role for achieving ah igh asymmetric induction but also affords chiral indole-containing products, which can be readily converted to ar ange of useful intermediates for the creation of chiral indole building blocks.

A convergent synthesis of 1,3,4-oxadiazoles from acyl hydrazides under semiaqueous conditions

“…13–16 The reaction of β-amino-α-bromo nitroalkane ( 3g ), and α-amino acid-derived acyl hydrazide ( 2o ), provide the enantiopure oxadiazole products ( 14 and 15 ), demonstrating that no racemization of either chiral α-bromo nitroalkane or amino acid hyrazide occurred during the oxadiazole formation.…”

“…Chiral, nonracemic α-bromo nitroalkanes are increasingly available in as little as a single step using enantioselective catalysis and bromonitromethane reagent. 13 – 16 The reaction of β-amino-α-bromo nitroalkane ( 3g ), and α-amino acid-derived acyl hydrazide ( 2o ), provide the enantiopure oxadiazole products ( 14 and 15 ), demonstrating that no racemization of either chiral α-bromo nitroalkane or amino acid hyrazide occurred during the oxadiazole formation.…”

“…Not only is the oxadiazole prepared in fewer steps than existing methodology, but preparative details are endowed with the advantages of UmAS: a mild, non-dehydrative preparation that avoids highly electrophilic reagents and high temperatures that would otherwise limit chemoselectivity. Furthermore, the increasing availability of α-bromo nitroalkanes ( 3 ) in enantioenriched form 13 – 16 further broadens the diversity of oxadiazoles now accessible.…”

Enantioselective “organocatalysis in disguise” by the ligand sphere of chiral metal-templated complexes

“…96 Since then, these catalysts have been widely employed in the enantioselective conjugate reduction of b,b-disubstituted nitroalkenes with Hantzsch esters and Friedel-Crafts alkylation of indoles with b,b-disubstituted nitroalkenes (Schemes 8-11). 96,97,108,[111][112][113][114] They demonstrated that the iridium(III) complex K-4 efficiently catalysed the enantioselective reduction of b,b-disubstituted nitroalkenes with a Hantzsch ester as the reducing agent at remarkably low catalyst loadings (up to 0.1 mol%) (Scheme 8). 96 The corresponding reduced (R)-nitroalkane products were obtained in high yields with excellent enantioselectivities (93-99% ee) (Scheme 8).…”

Expanding the Family of Octahedral Chiral-at-Metal Cobalt(III) Catalysts by Introducing Tertiary Amine Moiety into the Ligand

“…Chiral stereochemically inert, coordinatively saturated metal complexes of Co, Cr, Rh, Ir or Ru presented a perspective class of "organic catalysts in disguise" which were applied in various asymmetric organic reactions [1][2][3][4]. In these complexes, the metal center can play several important roles: (1) to activate the coordinated ligands converting them into efficient hydrogen bond donors/acceptors ; (2) to serve as a chiral center (metal-centered chirality) providing a well-defined chiral environment [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] (in case of octahedral geometry of the complexes due to the mutual meridional arrangement of the chiral or achiral ligands around the metal ion with Λ-(left-handed propeller) or ∆configurations (right-handed propeller)) [1][2][3][4][5][6][7][8][9][10][11][13][14][15][16][17][18][19][20][21][22]…”