Preparation of N-phenyl-(S)-prolinol-derived P,N-ligands and their application in Pd-catalyzed asymmetric allylic alkylation

Several NPN-type ligands bearing two chiral pyrrolidinyl groups derived from N-phenyl-(S)-prolinol were prepared by two synthetic methods. Their palladium-complex-catalyzed asymmetric allylic alkylation of malonates with 1,3-diphenyl 2-propenyl acetate delivered the products with good to high enantioselectivities (84–97% ee), including an optically active fluorine-containing compound.

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Bis[2-(S)-(2-methoxylmethylpyrrolidinyl)phenyl]phenyl phosphine oxideC30H37N2O3P[α]D20=+43 (c 1.00, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:2S,2′S

tert-Butyl bis[2-(S)-(2-methoxylmethylpyrrolidinyl)phenyl]phosphine oxideC28H41N2O3P[α]D20=+143 (c 1.02, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:2S,2′S

Bis[2-(S)-(2-methoxylmethylpyrrolidinyl)phenyl]phenyl phosphineC30H37N2O2P[α]D20=-165 (c 1.05, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:2S,2′S

(Sp)-[2-(S)-(2-Methoxylmethylpyrrolidinyl)phenyl] (2-methoxyl-phenyl)phenyl phosphine oxideC25H28NO3P[α]D20=+146 (c 1.05, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:S,Sp

(Rp)-[2-(S)-(2-Methoxylmethylpyrrolidinyl)phenyl] (2-methoxyl-phenyl)phenyl phosphine oxideC25H28NO3P[α]D20=-5 (c 1.00, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:S,Rp

(Rp)-[2-(S)-(2-Methoxylmethylpyrrolidinyl)phenyl] (2-methoxyl-phenyl)phenyl phosphine oxideC25H28NO2P[α]D20=-43 (c 0.84, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:S,Rp

(Sp)-[2-(S)-(2-Methoxylmethylpyrrolidinyl)phenyl] (2-methoxyl-phenyl)phenyl phosphine oxideC25H28NO2P[α]D20=-105 (c 0.94, CHCl3)Source of chirality: (S)-2-methoxylmethylpyrrolidineAbsolute configuration: S,Sp

(S)-(1-Phenylpyrrolidin-2-yl)methanolC11H15NO>99.8% ee[α]D20=-119 (c 1.15, CHCl3)Source of chirality: (S)-prolineAbsolute configuration: S

(S)-2-(Methoxymethyl)-1-phenylpyrrolidineC12H17NO[α]D20=-155 (c 1.04, CHCl3)Source of chirality: (S)-prolineAbsolute configuration: S

(S)-[1-(2-Diphenylphosphanylphenyl)pyrrolidin-2-yl]methanolC23H24NOP[α]D20=+3.4 (c 1.05, CHCl3)Source of chirality: (S)-prolineAbsolute configuration: S

(S)-(1-(2-Bromophenyl)pyrrolidin-2-yl)methanolC11H14BrNO[α]D20=+51 (c 1.16, CHCl3)Source of chirality: (S)-proline or (S)-prolinolAbsolute configuration: S

(S)-(1-(4-Bromophenyl)pyrrolidin-2-yl)methanolC11H14BrNO[α]D20=-79 (c 0.98, CHCl3)Source of chirality: (S)-prolineAbsolute configuration: S

(3aS)-2,3,3a,4-Tetrahydro-1H-5-oxa-9b-aza-cyclopenta[a]naphthaleneC11H13NO[α]D20=+46 (c 1.19, CHCl3)Source of chirality: (S)-proline or (S)-prolinolAbsolute configuration: S

(S)-1-(2-Bromophenyl)-2-(methoxymethyl)pyrrolidineC12H16BrNO[α]D20=+23 (c 1.30, CHCl3)Source of chirality: (S)-proline or (S)-prolinolAbsolute configuration: S

(S)-2-(Benzyloxymethyl)-1-(2-bromophenyl)pyrrolidineC18H20BrNO[α]D20=+3.8 (c 1.01, CHCl3)Source of chirality: (S)-prolineAbsolute configuration: S

tert-Butyl bis[2-(S)-(2-methoxylmethylpyrrolidinyl)phenyl]phosphineC28H41N2O2P[α]D20=-125 (c 1.10, CHCl3)Source of chirality: (S)-proline or (S)-prolinolAbsolute configuration: 2S,2′S

Bis-[2-(S)-(2-benzoxymethylpyrrolidinyl)phenyl]phenyl phosphineC42H45N2O2P[α]D20=-78 (c 0.90, CHCl3)Source of chirality: (S)-prolinolAbsolute configuration: 2S,2′S

(R,E)-Dimethyl 2-(1,3-diphenylallyl)-2-fluoromalonateC20H19FO484% ee[α]D20=+35 (c 0.22, CHCl3)Absolute configuration: R