Bicyclic phosphine-thiazole ligands for the asymmetric hydrogenation of olefins

New bicyclic thiazole-based chiral N,P-chelating ligands were developed. High activities and enantioselectivities were achieved in the iridium-catalyzed asymmetric hydrogenation of olefins with the new ligands.

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2-((1S,3R,4R)-2-Azabicyclo[2.2.1]heptan-3-yl)-4-methylthiazoleC10H14N2SEe = 100%[α]D23=+48.5 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)

2-((1S,3R,4R)-2-Azabicyclo[2.2.1]heptan-3-yl)-4-tert-butylthiazoleC13H20N2SEe = 100%[α]D23=+42.2 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)

2-((1S,3R,4R)-2-Azabicyclo[2.2.1]heptan-3-yl)-4-phenylthiazoleC15H16N2SEe = 100%[α]D23=+58.6 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)

2-((1S,3R,4R)-2-(Diphenylphosphino)-2-azabicyclo[2.2.1]heptan-3-yl)-4-methylthiazoleC22H23N2PSEe = 100%[α]D23=-2.9 (c 1, C6D6)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)

2-((1S,3R,4R)-2-(Diphenylphosphino)-2-azabicyclo[2.2.1]heptan-3-yl)-4-tert-butyl-thiazoleC25H29N2PSEe = 100%[α]D23=-5.0 (c 1, C6D6)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)

2-((1S,3R,4R)-2-(Diphenylphosphino)-2-azabicyclo[2.2.1]heptan-3-yl)-4-phenylthiazoleC27H25N2PSEe = 100%[α]D23=+3.1 (c 1, C6D6)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)

2-((1S,3R,4R)-2-(di-o-tolylphosphino)-2-azabicyclo[2.2.1]heptan-3-yl)-4-phenylthiazoleC29H29N2PSEe = 100%[α]D23=-81.1 (c 1, C6D6)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)

(η4-1,5-Cyclooctadiene) 2-((1S,3R,4R)-2-(diphenylphosphino)-2-azabicyclo[2.2.1]heptan-3-yl)-4-methylthiazole iridium(I) tetrakis[3,5-bis(trifluoromethyl)phenyl]borateC62H47BN2PSF24IrEe = 100%[α]D23=-35.5 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)

(η4-1,5-Cyclooctadiene) 2-((1S,3R,4R)-2-(diphenylphosphino)-2-azabicyclo[2.2.1]heptan-3-yl)-4-tert-butyl-thiazole iridium(I) tetrakis[3,5-bis(trifluoromethyl)phenyl]borateC65H53BN2PSF24IrEe = 100%[α]D23=+54.3 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)

(η4-1,5-Cyclooctadiene) 2-((1S,3R,4R)-2-(diphenylphosphino)-2-azabicyclo[2.2.1]heptan-3-yl)-4-methylthiazole iridium(I) tetrakis[3,5-bis(trifluoromethyl)phenyl]borateC67H49BN2PSF24IrEe = 100%[α]D23=+8.5 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)

(η4-1,5-Cyclooctadiene) 2-((1S,3R,4R)-2-(dio-tolylphosphino)-2-azabicyclo[2.2.1]heptan-3-yl)-4-phenylthiazole iridium(I) tetrakis[3,5-bis(trifluoromethyl)phenyl]borateC69H53BN2PSF24IrEe = 100%[α]D23=+14.5 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,4R)