A straightforward access to pyrrolidine-based ligands for asymmetric synthesis

A straightforward and flexible method for the preparation of ligands based on the pyrrolidine scaffold is presented. The synthetic strategy involves a diastereoselective allylation of phenylglycinol-derived imines, followed by a cyclization promoted by a hydrozirconation/halogenation sequence. Enantioselectivities of up to 84% ee in the asymmetric allylic allylation were obtained using these ligands.

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(R)-2-((R)-1-(2-Bromophenyl)but-3-enylamino)-2-phenylethanolC18H20BrNO[α]D20=-37.2 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

tert-Butyl (R)-1-(2-bromophenyl)-but-3-enylcarbamateC15H20BrNO2[α]D20=+38.9 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-1-(2-Bromophenyl)-N-methylbut-3-en-1-amineC11H14BrN[α]D20=+8.6 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-2-(2-Bromophenyl)-1-methylpyrrolidineC11H14BrN[α]D20=+89.8 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-1-Methyl-2-(2-(diphenylphosphino)phenyl)pyrrolidineC23H24NP[α]D20=+26.3 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-N-[(R)-2-(Pyridin-2-yl)but-3-enylamino]-2-phenylethanolC17H20N2O[α]D20=+10.0 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-1-(Pyridin-2-yl)but-3-en-1-amineC9H12N2[α]D20=+43.8 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

2-[(R)-Pyrrolidin-2-yl]pyridineC9H12N2[α]D20=+78.4 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

2-[(R)-1-(Diphenylphosphinoborane)pyrrolidin-2-yl]pyridineC21H24BN2P[α]D20=+81.0 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-2-[(R)-1-Ferrocenylbut-3-enylamino]-2phenylethanolC22H25FeNO[α]D20=-57.0 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-2-Phenyl-2-[(R)-ferrocenylpyrrolidin-1-yl]ethanolC22H25FeNO[α]D20=+14.0 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-2-FerrocenylpyrrolidineC14H17FeN[α]D20=+28.5 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-2-Ferrocenyl-1-methylpyrrolidineC15H19FeN[α]D20=+89.2 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-1-[2-(Diphenylphosphino)benzyl]-2-ferrocenylpyrrolidineC21H23FeNS C33H32FeNP[α]D20=+81.1 (c 1, CH2Cl2)Source of chirality (R)-phenylglycinol Absolute configuration: (R)

(R)-1-Methyl-2-[(p-R)-(2-phenylthio)ferrocenyl]pyrrolidineC21H23FeNS[α]D20=+211.9 (c 1, CH2Cl2)Source of chirality: diastereoselective metallation Absolute configuration: (2′R, 1pR)

(R)-1-Methyl-2-[(p-R)-(2-diphenylphosphino)ferrocenyl]pyrrolidineC27H28FeNP[α]D20=+255.5 (c 1, CHCl3)Source of chirality: diastereoselective metallation Absolute configuration: (2′R, 1pR)

(R)-1-Methyl-2-[(p-R)-(2-diethoxyphosphino)ferrocenyl]pyrrolidineC19H28FeNO2P[α]D20=+222.3 (c 1, CH2Cl2)Source of chirality: diastereoselective metallation Absolute configuration: (2′R, 1pR)

(R)-1-Methyl-2-[(p-R)-(trimethylslyl)ferrocenyl]pyrrolidineC18H27FeNSi[α]D20=+89.0 (c 0.4, CHCl3)Source of chirality: diastereoselective metallation Absolute configuration: (2′R, 1pR)

(R)-1-Methyl-2-[(p-S)-2-(diphenylphosphino)-5-(trimethylsilyl)ferrocenyl]pyrrolidineC30H36FeNPSi[α]D20=-98.2 (c 1, CH2Cl2)Source of chirality: regioselective metallation Absolute configuration: (2′R, 1pS)

(R)-1-Methyl-2-[(p-S)-2-(diphenylphosphino)ferrocenyl]pyrrolidineC27H28FeNP[α]D20=-339.0 (c 0.6, CH2Cl2)Source of chirality: regioselective metallation Absolute configuration: (2′R, 1pS)