A new chiral phosphine oxide ligand for enantioselective 1,3-dipolar cycloaddition reactions of azomethine ylides

A new set of phosphorus-containing chiral ligands has been synthesized and used with silver(I) for the catalytic asymmetric 1,3-dipolar cycloaddition reaction of azomethine ylides. One of these ligands (POFAM6) was found to produce an effective catalyst for the asymmetric 1,3-dipolar cycloaddition reaction of azomethine ylides with electron deficient dipolarophiles to form pyrrolidines in up to 97% yield and 89% ee.

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((R)-1-((R)-1-Hydroxybutan-2-yl)aziridin-2-yl)(ferrocenyl)methanoneC17H21FeNO2Ee = 100%[α]D22=-112.5 (c 0.5, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

((S)-1-((R)-1-Hydroxybutan-2-yl)aziridin-2-yl)(ferrocenyl)methanoneC17H21FeNO2Ee = 100%[α]D22=+93.6 (c 0.5, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R)

(R)-2-((R)-2-Ferrocenoylaziridin-1-yl)butyl 4-methylbenzenesulfonateC24H27FeNO4SEe = 100%[α]D22=-138.9 (c 1.0, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(R)-2-((S)-2-Ferrocenoylaziridin-1-yl)butyl 4-methylbenzenesulfonateC24H27FeNO4SEe = 100%[α]D22=+95.7 (c 0.98, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R)

Ferrocenyl((R)-1-((R)-1-(diphenylphosphino)butan-2-yl)aziridin-2-yl)methanoneC29H30FeNOP[α]D22=+13.0 (c 0.5, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

Ferrocenyl((R)-1-((R)-1-(diphenylphosphinoxy)butan-2-yl)aziridin-2-yl)methanoneC29H30FeNO2P[α]D22=+21.4 (c 0.4, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(R)-Ferrocenyl((R)-1-((R)-1-(diphenylphosphinoxy)butan-2-yl)aziridin-2-yl)methanolC29H32FeNO2P[α]D28=-20.9 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R,R)

(S)-Ferrocenyl((R)-1-((R)-1-(diphenylphosphinoxy)butan-2-yl)aziridin-2-yl)methanolC29H32FeNO2P[α]D22=+32.8 (c 1.5, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R,R)

Ferrocenyl((S)-1-((R)-1-(diphenylphosphino)butan-2-yl)aziridin-2-yl)methanoneC29H30FeNOP[α]D22=+45.9 (c 1.0, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R)

Ferrocenyl((S)-1-((R)-1-(diphenylphosphino)butan-2-yl)aziridin-2-yl)methanoneC29H30FeNO2P[α]D22=+75.8 (c 1.0, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R)

(S)-Ferrocenyl((S)-1-((R)-1-(diphenylphosphino)butan-2-yl)aziridin-2-yl)methanolC29H32FeNOP[α]D22=-13.3 (c 0.5, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S,R)

(R)-Ferrocenyl((S)-1-((R)-1-(diphenylphosphino)butan-2-yl)aziridin-2-yl)methanolC29H32FeNOP[α]D22=+12.2 (c 1.0, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S,R)

(2S,4S,5R)-Dimethyl 5-(naphthalen-1-yl)pyrrolidine-2,4-dicarboxylateC18H19NO4Ee = 76%[α]D20=+144.4 (c 1.3, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,4S,5R)

(1S,3R,3S,6R)-Methyl octahydro-5-methyl-3-(naphthalen-1-yl)-4,6-dioxopyrrolo[3,4-c]pyrrole-1-carboxylateC19H18N2O4Ee = 47%[α]D20=+72.2 (c 1.3, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R,3S,6R)