Synthesis of planar chiral [2.2]paracyclophane monophosphine ligands and their application in the umpolung allylation of aldehydes

Chiral [2.2]paracyclophane monophosphines 8 were synthesized via resolution using chiral palladacycle 10. Chiral phosphinite 5 was also prepared from 4-hydroxy[2.2]paracyclophane. Phosphines 8 and phosphinite 5 were used as the ligand in the umpolung allylation of aldehydes 14 with cyclohexenyl acetate 15, giving homoallyl alcohols 16 in high diastereoselectivity and in moderate to good enantioselectivity. Palladacycle 10 was recovered by treating the palladacycle–phosphine complexes with sodium prolinate, followed by treatment with HCl in high yield.

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(S,Sp)-[2,2]Paracyclophan-4′yl 2-(6-methoxynaphthalen-2-yl)propanoateC30H28O3[α]D20=+48.5 (c 0.58, CH2Cl2)Source of chirality: (S)-naproxen acidAbsolute configuration: (Sp,S)

(S,Rp)-[2,2]Paracyclophan-4′-yl 2-(6-methoxynaphthalen-2-yl)propanoateC30H28O3[α]D20=+31.9 (c 1.05, CH2Cl2)Source of chirality: (S)-naproxen acidAbsolute configuration: (Rp,S)

(Rp)-Diphenyl([2.2]paracyclophan-4-yl)phosphiniteC28H25OP[α]D20=-24.1 (c 1.05, CHCl3)Source of chirality: (S)-naproxen acidAbsolute configuration: (Rp)

(Sp)-Diphenyl([2.2]paracyclophan-4-yl)phosphineC28H25P[α]D20=-15.1 (c 1.0, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Sp)

Chloro[(S)-dimethyl(1-(1-naphthyl)ethyl)aminato-C,N][(Rp)-diphenyl([2.2]paracyclophan-4-yl)phosphine]palladium(II)C42H41ClNPPd[α]D20=-34.0 (c 1.10, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Rp,S)

Chloro[(S)-dimethyl(1-(1-naphthyl)ethyl)aminato-C,N][(Sp)-diphenyl([2.2]paracyclophan-4-yl)phosphine]palladium(II)C42H41ClNPPd[α]D20=-163.9 (c 0.6, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Sp,S)

Chloro[(S)-dimethyl(1-(1-naphthyl)ethyl)aminato-C,N][(Rp)-di(4′-methoxy)([2.2]paracyclophan-4-yl)phosphine]palladium(II)C44H45ClNO2PPd[α]D20=-30.2 (c 0.78, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Rp,S)

Chloro[(S)-dimethyl(1-(1-naphthyl)ethyl)aminato-C,N][(Sp)-di(4′-methoxy)([2.2]paracyclophan-4-yl)phosphine]palladium(II)C44H45ClNO2PPd[α]D20=-238 (c 0.97, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Sp,S)

Chloro[(S)-dimethyl(1-(1-naphthyl)ethyl)aminato-C,N][(Rp)-di(4′-trifluoromethyl)phenyl-([2.2]paracyclophan-4-yl)phosphine]palladium(II)C44H39ClF6NPPd[α]D20=-5.1 (c 1.0, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Rp,S)

Chloro[(S)-dimethyl(1-(1-naphthyl)ethyl)aminato-C,N][(Sp)-di(4′-trifluoromethyl)phenyl-([2.2]paracyclophan-4-yl)phosphine]palladium(II)C44H39ClF6NPPd[α]D20=-141.5 (c 1.14, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Sp,S)

Chloro[(S)-dimethyl(1-(1-naphthyl)ethyl)aminato-C,N][(Rp)-di(3′,5′-dimethylphenyl)([2.2]paracyclophan-4-yl)phosphine]palladium(II)C46H49ClNPPd[α]D20=-30.1 (c 0.56, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Rp,S)

Chloro[(S)-dimethyl(1-(1-naphthyl)ethyl)aminato-C,N][(Sp)-di(3′,5′-dimethylphenyl)([2.2]paracyclophan-4-yl)phosphine]palladium(II)C46H49ClNPPd[α]D20=-231.2 (c 0.82, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Sp,S)

Chloro[(S)-dimethyl(1-(1-naphthyl)ethyl)aminato-C,N][(Rp)-dicyclohexyl([2.2]paracyclophan-4-yl)phosphine]palladium(II)C42H53ClNPPd[α]D20=+18.9 (c 0.80, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Rp,S)

Chloro[(S)-dimethyl(1-(1-naphthyl)ethyl)aminato-C,N][(Sp)-dicyclohexyl([2.2]paracyclophan-4-yl)phosphine]palladium(II)C42H53ClNPPd[α]D20=-22.5 (c 0.82, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Sp,S)

(Sp)-Di(4′-methoxyphenyl)([2.2]paracyclophan-4-yl)phosphineC30H29O2P[α]D20=-37.6 (c 0.18, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Sp)

(Sp)-Di(4′-trifluoromethylphenyl)([2.2]paracyclophan-4-yl)phosphineC30H23F6P[α]D20=-11.2 (c 0.27, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Sp)

(Sp)-Di(3′,5′-dimethylphenyl)([2.2]paracyclophan-4-yl)phosphineC32H33P[α]D20=-12.6 (c 0.40, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Sp)

(Sp)-Dicyclohexyl([2.2]paracyclophan-4-yl)phosphineC28H37P[α]D20=-44.6 (c 0.20, CHCl3)Source of chirality: (S)-1-(naphthalen-1-yl)ethanamineAbsolute configuration: (Sp)