Synthesis of new fluorous modular chiral ligand derivatives from amino alcohols and application in enantioselective carbon–carbon bond-forming alkylation reactions

N-Trifluoracyl β-chalcogeno amides and N-perfluoracyl β-thio amide ligands were prepared by a simple and efficient reaction sequence. These new ligands were evaluated in palladium-catalyzed alkylation of rac-(E)-1,3-diphenyl-2-propenyl acetate in the presence of dimethyl malonate and an enantioselectivity of up to 99% was obtained. After catalysis, the fluorous ligand can be easily recovered by liquid–liquid extraction and reused without loss in the activity.

Figure optionsDownload as PowerPoint slide

(S)-2,2,2-Trifluoro-N-(3-methyl-1-(phenylselanyl)butan-2-yl)acetamideC13H16F3NOSe[α]D20=+4 (c 3, CH2Cl2)Absolute configuration: (S)

(S)-2,2,2-Trifluoro-N-(3-methyl-1-(phenylthio)butan-2-yl)acetamideC13H16F3NOS[α]D20=-0.8 (c 3, CH2Cl2)Absolute configuration: (S)

(S)-2,2,2-Trifluoro-N-(3-methyl-1-(phenyltellanyl)butan-2-yl)acetamideC13H16F3NOTe[α]D20=+13 (c 3, CH2Cl2)Absolute configuration: (S)

(S)-N-(1-(Diphenylphosphino)-3-methylbutan-2-yl)-2,2,2-trifluoroacetamideC19H21F3NOP[α]D20=+25 (c 1, CH2Cl2)Absolute configuration: (S)

(S)-2,2,2-Trifluoro-N-(1-(4-methoxyphenylthio)-3-methylbutan-2-yl)acetamideC14H18F3NO2S[α]D20=+19 (c 3, CH2Cl2)Absolute configuration: (S)

(S)-N-(1-(4-Chlorophenylthio)-3-methylbutan-2-yl)-2,2,2-trifluoroacetamideC13H15ClF3NOS[α]D20=+10 (c 3, CH2Cl2)Absolute configuration: (S)

(S)-2,2,2-Trichloro-N-(3-methyl-1-(phenylthio)butan-2-yl)acetamideC13H16Cl3F3NOS[α]D20=+32 (c 3, CH2Cl2)Absolute configuration: (S)

(S)-2,2,2-Trichloro-N-(1-oxo-1-phenyl-3-(phenylthio)propan-2-yl)acetamideC17H16F3NOS[α]D20=+39 (c 3, CH2Cl2)Absolute configuration: (S)

(S)-2,2,3,3,4,4,5,5,6,6,7,7,7-Tridecafluoro-N-(3-methyl-1-(phenylthio)butan-2-yl)heptanamideC18H16F13NOS[α]D20=+39 (c 3, CH2Cl2)Absolute configuration: (S)