Iridium-catalyzed asymmetric hydrogenation of olefins using TIQ phosphine–oxazoline ligands

A novel family of tetrahydroisoquinoline (TIQ) phosphine–oxazoline ligands and four corresponding iridium complexes have been developed and applied to the asymmetric hydrogenation of unfunctionalized olefins. The results showed that the best conversion rates were observed in up to 99% with an enantiomeric excess of 91%.

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(S)-Benzyl 3-((R)-2-hydroxy-1-phenylethylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateC26H26N2O4[α]D20=-26.2 (c 0.42, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,3R)

(S)-Benzyl 3-((S)-2-hydroxy-1-phenylethylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateC26H26N2O4[α]D20=+10.7 (c 0.70, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,3S)

(S)-Benzyl 3-((R)-1-hydroxy-3-methylbutan-2-ylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateC23H28N2O4[α]D20=+4.4 (c 0.80, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,3R)

(S)-Benzyl 3-((S)-1-hydroxy-3-methylbutan-2-ylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateC23H28N2O4[α]D20=23.1 (c 1.17, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,3S)

(S)-Benzyl 3-((R)-4-phenyl-4,5-dihydrooxazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylateC26H24N2O3[α]D20=+2.7 (c 0.37, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,3R)

(S)-Benzyl 3-((S)-4-phenyl-4,5-dihydrooxazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylateC26H24N2O3[α]D20=+12.2 (c 0.41, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,3S)

(S)-Benzyl 3-((R)-4-isopropyl-4,5-dihydrooxazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylateC23H26N2O3[α]D20=+3.4 (c 0.89, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,3R)

(S)-Benzyl 3-((S)-4-isopropyl-4,5-dihydrooxazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylateC23H26N2O3[α]D20=9.7 (c 0.72, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,3S)

(R)-4-Phenyl-2-((S)-1,2,3,4-tetrahydroisoquinolin-3-yl)-4,5-dihydrooxazoleC18H18N2O[α]D20=+46.15 (c 0.26, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1R,2S)

(S)-4-Phenyl-2-((S)-1,2,3,4-tetrahydroisoquinolin-3-yl)-4,5-dihydrooxazoleC18H18N2O[α]D20=7.4 (c 1.85, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,2S)

(R)-4-Isopropyl-2-((S)-1,2,3,4-tetrahydroisoquinolin-3-yl)-4,5-dihydrooxazoleC15H20N2O[α]D20=12.7 (c 0.55, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1R,2S)

(S)-4-Isopropyl-2-((S)-1,2,3,4-tetrahydroisoquinolin-3-yl)-4,5-dihydrooxazoleC15H20N2O[α]D20=10.9 (c 0.69, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,2S)

(η4-1,5-Cyclooctadiene) (R)-2-((S)-2-(diphenylphosphino)-1,2,3,4-tetrahydroisoquinolin-3-yl)-4-phenyl-4,5-dihydrooxazole iridium(I) tetrakis[3,5-bis(trifluoromethyl)phenyl]borateC70H51BN2PF24OIr[α]D20=3.1 (c 0.32, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1R,2S)

(η4-1,5-Cyclooctadiene) (S)-2-((S)-2-(diphenylphosphino)-1,2,3,4-tetrahydroisoquinolin-3-yl)-4-phenyl-4,5-dihydrooxazole iridium(I) tetrakis[3,5-bis(trifluoromethyl)phenyl]borateC70H51BN2PF24OIr[α]D20=+40.9 (c 1.15, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,2S)

(η4-1,5-Cyclooctadiene) (R)-2-((S)-2-(diphenylphosphino)-1,2,3,4-tetrahydroisoquinolin-3-yl)-4-isopropyl-4,5-dihydrooxazole iridium(I) tetrakis[3,5-bis(trifluoromethyl)phenyl]borateC67H53BN2PF24OIr[α]D20=+1.6 (c 0.64, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1R,2S)

(η4-1,5-Cyclooctadiene) (S)-2-((S)-2-(diphenylphosphino)-1,2,3,4-tetrahydroisoquinolin-3-yl)-4-isopropyl-4,5-dihydrooxazole iridium(I) tetrakis[3,5-bis(trifluoromethyl)phenyl]borateC67H53BN2PF24OIr[α]D20=+30.2 (c 0.86, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1S,2S)