Rational tuning of the rigidity of a ligand scaffold: synthesis of diphenylsulfide-linked bis(oxazoline) ligands and their application in asymmetric allylic alkylation

The scaffold rigidity of bis(oxazoline) ligands was rationally tuned on the basis of literature information. Diphenylsulfide-linked bis(oxazoline) ligands with a flexible scaffold were efficiently synthesized to test our hypothesis. The improved enantioselectivity in palladium-catalyzed asymmetric allylic alkylation reaction was achieved as we expected.

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2,2′-Bis[N-[(S)-2-hydroxy-1-phenylethyl]carbamoyl]-1,1′-diphenylsulfideC30H28N2O4S[α]D20=-12.9 (c 0.7, CH2Cl2)Source of chirality: (S)-2-phenylglycinolAbsolute configuration: (S,S)

2,2′-Bis[N-[(S)-1-hydroxymethyl-2-phenylethyl]carbamoyl]-1,1′-diphenylsulfideC32H32N2O4S[α]D20=-69.3 (c 0.6, CH2Cl2)Source of chirality: (S)-phenylalaninolAbsolute configuration: (S,S)

2,2′-Bis[N-[(S)-1-hydroxymethyl-2-methylpropyl]carbamoyl]-1,1′-diphenylsulfideC24H32N2O4S[α]D20=-55.4 (c 0.7, CH2Cl2)Source of chirality: (S)-valinolAbsolute configuration: (S,S)

2,2′-Bis[N-[(S)-2,2-dimethyl-1-hydroxymethylpropyl]carbamoyl]-1,1′-diphenylsulfideC26H36N2O4S[α]D20=-16.7 (c 0.3, DMSO)Source of chirality: (S)-tert-leucinolAbsolute configuration: (S,S)

2,2′-Bis[(S)-4-phenyloxazolin-2-yl]-1,1′-diphenylsulfideC30H24N2O2S[α]D20=-2.5 (c 0.7, CH2Cl2)Source of chirality: (S)-2-phenylglycinolAbsolute configuration: (S,S)

2,2′-Bis[(S)-4-benzyloxazolin-2-yl]-1,1′-diphenylsulfideC32H28N2O2S[α]D20=-36.9 (c 0.6, CH2Cl2)Source of chirality: (S)-phenylalaninolAbsolute configuration: (S,S)

2,2′-Bis[(S)-4-isopropyloxazolin-2-yl]-1,1′-diphenylsulfideC24H28N2O2S[α]D20=-22.2 (c 0.6, CH2Cl2)Source of chirality: (S)-valinolAbsolute configuration: (S,S)

2,2′-Bis[(S)-4-tert-butyloxazolin-2-yl]-1,1′-diphenylsulfideC26H32N2O2S[α]D20=-108.6 (c 0.3, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (S,S)

(S)-Diethyl 2-[(E)-1,3-diphenylprop-2-en-1-yl]malonateC22H24O4Ee = 91%[α]D20=-7.9 (c 2.3, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Dimethyl 2-[(E)-1,3-diphenylprop-2-en-1-yl]malonateC20H20O4Ee = 89%[α]D20=-10.7 (c 0.7, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1,3-Dimethyl-5-[(E)-1,3-diphenylprop-2-en-1-yl]barbituric acidC21H20N2O2Ee = 85%[α]D20=+67.8 (c 0.7, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Diethyl 2-[(E)-1,3-bis(naphth-1-yl)prop-2-en-1-yl]malonateC30H28O4Ee = 94%[α]D20=+33.6 (c 0.8, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Dimethyl 2-[(E)-1,3-bis(naphth-1-yl)prop-2-en-1-yl]malonateC28H24O4Ee = 94%[α]D20=+46.9 (c 0.6, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1,3-Dimethyl-5-[(E)-1,3-bis(naphth-1-yl)prop-2-en-1-yl]barbituric acidC29H24N2O3Ee = 42%[α]D20=+37.8 (c 0.67, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)