Enantioselective iminium-catalyzed epoxidation of hindered trisubstituted allylic alcohols

The reactivity of diastereomeric biaryl iminium cations made of a (Ra)-5,5′,6,6′,7,7′,8,8′-octahydrobinaphthyl core and exocyclic appendages derived from (S)- or (R)-3,3-dimethylbutyl-2-amine was investigated with hindered trisubstituted allylic alcohols—a class of alkenes which had not been previously studied in detail in epoxidation reactions with cyclic iminium catalysts (ee up to 98%). Surprisingly, generally strong matched/mismatched effects are observed not only in terms of reactivity but also on the enantioselectivity of the reaction (Δee up to 16%). Also, for the most hindered substrates, two sets of reaction conditions were tested in a preliminary study and little advantage was found in running reactions in MeCN/water instead of CH2Cl2/water/18-C-6. In any case, the presence of the hydroxyl group did not reveal any anchimeric effect.

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(−)-(S)-3,3-DiphenyloxiranemethanolC15H14O2Ee 88%[α]D25=-16.6 (c 0.5, CHCl3)Source of chirality: enantioselective catalysisAbsolute configuration: (S)

(−)-1,1-Diphenyl-3-methoxyprop-2-ene oxideC16H16O2Ee 87%[α]D25=-28.6 (c 1.0, CHCl3)Source of chirality: enantioselective catalysisAbsolute configuration: levorotatory

(+)-trans-3-Ethyl-3-phenyloxiranemethanolC11H14O2Ee 87%[α]D25=5.3 (c 1.0, CHCl3)Source of chirality: enantioselective catalysisAbsolute configuration: dextrorotatory

(+)-trans-3-Isobutyl-3-phenyloxiranemethanolC13H18O2Ee 91%[α]D25=20.4 (c 1.0, CHCl3)Source of chirality: enantioselective catalysisAbsolute configuration: dextrorotatory

(+)-trans-3-Isopropyl-3-phenyloxiranemethanolC12H16O2Ee 95%[α]D25=33.0 (c 1.0, CHCl3)Source of chirality: enantioselective catalysisAbsolute configuration: dextrorotatory

(+)-trans-3-Isopropyl-3-(4-methylphenyl)oxiranemethanolC13H18O2Ee 95%[α]D25=25.9 (c 1.0, CHCl3)Source of chirality: enantioselective catalysisAbsolute configuration: dextrorotatory

(+)-(2S,3S)-trans-3-Cyclohexyl-3-phenyloxiranemethanolC15H20O2Ee 98%[α]D25=42 (c 1.0, CHCl3)Source of chirality: enantioselective catalysisAbsolute configuration: (2S,3S)

(+)-trans- 3-(4-Bromophenyl)-3-cyclohexyloxiranemethanolC15H19BrO2Ee 79%[α]D25=26.1 (c 1.0, CHCl3)Source of chirality: enantioselective catalysisAbsolute configuration: dextrorotatory