Aziridin-2-yl methanols as organocatalysts in Diels–Alder reactions and Friedel–Crafts alkylations of N-methyl-pyrrole and N-methyl-indole

A series of enantiomerically pure aziridin-2-yl methanols have been synthesized from aziridine-2-carboxylic esters and have been tested as organocatalysts in Diels–Alder reactions and Friedel–Crafts alkylations of N-methyl-pyrrole and N-methyl-indole using α,β-unsaturated aldehydes. Moderate to good ee’s have been obtained. The coupling of N-methyl-pyrrole with crotonaldehyde and cinnamaldehyde using (2S,3S)-3-methylazirin-2-yl(diphenyl)methanol-TFA salt as the catalyst gave the best results (ee 75%).

Figure optionsDownload as PowerPoint slide

(2S)-1-Tritylaziridin-2-ylbis[4-(trifluoromethyl)phenyl]methanolC36H27F6NOEe >99%[α]D20=-76.1 (c 0.72, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

((S)-Aziridin-2-yl)bis[4-(trifluoromethyl)phenyl]methanolC17H13F6NOEe >99%[α]D20=-14.7 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

((S)-Aziridin-2-yl)diphenylmethanol-HCl saltC15H16ClNOEe >99%[α]D20=+44.9 (c 1.00, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(2S,3S)-3-Methylaziridin-2-yl(diphenyl)methanol-HCl saltC16H18ClNOEe >99%[α]D20=+44.9 (c 1.00, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

((S)-Aziridin-2-yl)bis[4-(trifluoromethyl)phenyl]methanol-HCl saltC17H14ClF6NOEe >99%[α]D20=+44.5 (c 0.6, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

((S)-Aziridin-2-yl)diphenylmethanol-TFA saltC17H16F3NO3Ee >99%[α]D20=+31.3 (c 0.67, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(2S,3S)-3-Methylaziridin-2-yl(diphenyl)methanol-TFA saltC18H18F3NO3Ee >99%[α]D20=+35.2 (c 0.885, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)