The design, synthesis and application of imidazolium-tagged ferrocenyl oxazoline phosphine ligands for the asymmetric 1,3-dipolar cycloaddition of azomethine ylides with nitroalkenes: ion effect for enhancing the reactivity, stereoselectivity and recyclab

A series of imidazolium moiety tagged planar chiral ferrocenyl oxazoline phosphine (FimiOAXP) ligands were designed and synthesised. In connection with their usefulness as ligands for asymmetric 1,3-dipolar cycloadditions of azomethine ylides with nitroalkenes, the catalysts were prepared in situ by treatment of copper(I) perchlorate and FimiOAXP. In the presence of a weak base, the pyrrolidine analogues were obtained in satisfactory yields and with excellent enantioselectivities (up to 99% ee). Through the experimental and computational outcomes, ion effect between the imidazolium moiety and azomethine ylide proved to be an essential factor for the excellent enantioselectivity. Moreover, with the benefit of the imidazolium moiety, the asymmetric 1,3-dipolar cycloaddition underwent in DCM/ionic liquids combined solvent for the first time. Taking advantage of the occasion, the catalyst could be recycled and reused for at least five times.

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(R)-4-Hydroxymethyl-2-ferrocenyloxazolineC14H15FeNO2[α]D20 = +84.0 (c 0.05, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-4-(tert-Butyldimethylsilyloxy)methyl-2-ferrocenyloxazolineC20H29FeNO2Si[α]D20 = +24.1 (c 0.28, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,Rp)-4-(tert-Butyldimethylsilyloxy)methyl-2-[(2-diphenylphosphino)ferrocenyl]oxazolineC32H38FeNO2PSi[α]D20 = +82.4 (c 0.24, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S,Rp)

(R,Rp)-4-Hydroxymethyl-2-[(2-diphenylphosphino)ferrocenyl]oxazolineC26H24FeNO2P[α]D20 = +246.0 (c 0.12, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,Rp)

(R,Rp)-1-[2-[2-(Diphenylphosphino)ferrocenyl]oxazolinyl]methyl-2,3-dimethylimidazole, trifluoromethyl sulfonateC32H31F3FeN3O4PS[α]D20 = +261.6 (c 0.17, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,Rp)

(R,Rp)-1-[2-[2-(Diphenylphosphino)ferrocenyl]oxazolinyl]methyl-2,3-dimethylimidazole, hexafluorophosphateC31H31F6FeN3OP2[α]D20 = +296.1 (c 0.10, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,Rp)

(R,Rp)-1-[2-[2-(Diphenylphosphino)ferrocenyl]oxazolinyl]methyl-2,3-dimethylimidazole, tetrafluoroborateC31H31BF4FeN3OP[α]D20 = +326.0 (c 0.10, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,Rp)

(R,Rp)-1-[2-[2-(Diphenylphosphino)ferrocenyl]oxazolinyl]methyl-2,3-dimethylimidazole, iodideC31H31FeIN3OP[α]D20 = +239.3 (c 0.22, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,Rp)

(R,Rp)-1-[2-[2-(Diphenylphosphino)ferrocenyl]oxazolinyl]methyl-2,3-dimethylimidazole, perchlorateC31H31ClFeIN3O5P[α]D20 = +298.1 (c 0.11, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,Rp)