Helical Chiral Pyridine N‐Oxides: A New Family of Asymmetric Catalysts

Abstract

Optically active chiral alkyl chlorides are valuable compounds because of their bioactivity and versatile synthetic utility. Accordingly, the ring opening of epoxides with a chloride nucleophile stands as an important goal in asymmetric catalysis. We describe herein recent advances in the design and development of chiral pyridine N-oxide catalysts for the enantioselective synthesis of chlorohydrins.

Helicene-Based Chiral Auxiliaries and Chirogenesis

“…Indeed, the first use of unsubstituted aza [6]helicene 81 and 82 as an organocatalyst for the kinetic resolution of alcohols rationalized the corresponding steric constraint imposed at the 1-position for a bulky acyl moiety and its subsequent group transfer reaction to rac-alcohols. However, the additionally functionalized 1-aza [6]helicene was found to be an effective asymmetric catalyst for various reactions [65,66], probably due to the facile access to reactants in the chiral cavity in the transition state, as demonstrated in the following examples.…”

Vibrational and electronic circular dichroism studies on the axially chiral pyridine-N-oxide: trans-2,6-di-ortho-tolyl-3,4,5-trimethylpyridine-N-oxide

“…Their stereochemical diversity is relatively rich involving axial chirality, 8,10,15,19,21,26 axial plus central chirality, 12,14,23,24,28 multicentered chirality originating in monoterpene units, 11,13,14,30 and planar 25 and helical chirality. 27 Since each type of chirality has its inherent structural feature, a variety of procedures has been used for establishing the absolute configuration of enantiopure pyridine-N-oxides. Reliable configurational assignments have been obtained by X-ray analysis of crystalline derivatives with optically active reagents (R)-and (S)-BINOL.…”

“…[1][2][3][4][5] Typical reactions tested so far for enantioselectivity include allylations of aldehydes with polyhalosilanes, [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] aldol additions of trichlorosilylenol ethers to aldehydes 6,7,22 or ketones, 23,24 and epoxide ring openings [25][26][27] as typical tested enantioselective reactions.…”

Asymmetric Henry Reaction of 2-Acylpyridine N-Oxides Catalyzed by a Ni-Aminophenol Sulfonamide Complex: An Unexpected Mononuclear Catalyst

“…Although Matsunaga and Shibasaki reported the kinetic resolution of racemic derivatives [30], the asymmetric catalytic version of simple ketones has experienced little progress. At the same time, interest in pyridine derivatives has increased dramatically with the discovery of many bioactive compounds [31,32,33] and ligands containing pyridine rings [34,35,36,37,38,39]. Pedro and Blay first extended the Henry reactions to 2-acylpyridine N -oxides, which provided a convenient way for synthesizing β-amino tert -alcohols substructure bearing a quaternary stereocenter bonded to a 2-pyridyl moiety [40].…”