Chiral amine–imine ligands based on trans-2,5-disubstituted pyrrolidines and their application in the palladium-catalyzed allylic alkylation

A series of amine–imine bidentate ligands based on a trans-2,5-disubstituted pyrrolidine and pyridine moieties have been prepared. The use of these ligands in the palladium-catalyzed allylic alkylation reaction of rac-(E)-1,3-diphenylprop-2-enyl acetate is reported. The results suggest that these ligands are good catalyst precursors for the reaction. Electronic modification on the pyridine ring of the ligands does not have a significant effect on the enantioselectivity of the reaction but does on the reaction rate, while structural modification on either the pyridine or the pyrrolidine moiety affords dramatic changes on the outcome of the stereochemistry. Evidence from various studies suggested that during the palladium-catalyzed allylic alkylation reaction, nucleophilic attack onto the 1,3-diphenylallyl moiety in the transition state occurs mainly trans to the pyridine ring of the less stable conformation of the palladium complexes.

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(1S,4S)-1,4-Di(4-methylphenyl)-1,4-butandiolC18H22O2Ee 99.5%[α]D25=-47.0 (c 0.65, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,4S)

(1S,4S)-1,4-Di(4-tert-butylphenyl)-1,4-butandiolC24H34O2Ee >95%[α]D25=-31.3 (c 1.14, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,4S)

(1S,4S)-1,4-Di(naphth-1-yl)-1,4-butandiolC24H22O2Ee 99.3%[α]D25=-68.0 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,4S)

(2R,5R)-1-Allyl-2,5-di-(4-tert-butylphenyl)pyrrolidineC27H37N[α]D25=+111.5 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)

(2R,5R)-2,5-Di-(4-tert-butylphenyl)pyrrolidineC24H33NEe >99%[α]D25=+106.5 (c 1.13, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)

2-[(2R,5R)-2,5-Diphenylpyrrolidin-1-yl]methylpyridineC23H25N2Ee >99%[α]D25=+131.6 (c 0.08, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)

2-[(2R,5R)-2,5-Diphenylpyrrolidin-1-yl]ethylpyridineC23H25N2[α]D25=+116.2 (c 0.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)

2-[(2R,5R)-2,5-Diphenylpyrrolidin-1-yl]methyl-4-nitropyridineC22H22N3O2Ee >98%[α]D23=+61.5 (c 1.3, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)

2-[(2R,5R)-2,5-Diphenylpyrrolidin-1-yl]methyl-4-methoxypyridineC23H25N2OEe >98%[α]D23=+81.7 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)

2-[(2R,5R)-2,5-Diphenylpyrrolidin-1-ylmethyl]-6-methylpyridineC18H22O2Ee >98%[α]D23=+132 (c 1.15, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)

2-[(2R,5R)-2,5-Diphenylpyrrolidin-1-ylmethyl]-4-methoxy-6-methylpyridineC24H26N2OEe >98%[α]D23=+94.7 (c 1.28, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)

2-[(2R,5R)-(2,5-Diphenylpyrrolidin-1-ylmethyl)]quinolineC26H25N2Ee >98%[α]D28=+141.2 (c 1.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)

2-[(2R,5R)-2,5-Bis(4-methylphenyl)pyrrolidin-1-ylmethyl]pyridineC24H26N2Ee >99%[α]D23=+159.7 (c 0.96, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)

2-[2,5-Bis-(4-tert-butylphenyl)pyrrolidin-1-ylmethyl]pyridineC18H22O2Ee >98%[α]D23=+125.4 (c 1.15, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,5R)