Improved conditions for the asymmetric synthesis of α-amino acids using Cinchona-derived anthracenylmethyl ammonium salts as chiral phase-transfer organocatalysts

Cinchonidine and cinchonine-derived monomeric anthracenylmethyl ammonium salts bearing different counter-anions are used as chiral organocatalysts in the enantioselective alkylation of a benzophenone-imine tert-butyl glycinate under phase-transfer conditions. Generally, an improvement of the enantioselectivity is observed when the counterions are tetrafluoroborate and hexafluorophosphate using 50% aqueous KOH as the base and toluene/chloroform as the solvent. The enantioselectivities achieved are comparable and frequently higher, even working under simpler and less-strict reaction conditions and with lower organocatalyst loading, than those reported previously.

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N-9-Anthracenylmethylcinchonidinium tetrafluoroborateC34H33BF4N2O[α]D25=-316 (c 0.7, acetone)Source of chirality: (−)-cinchonidine

N-9-Anthracenylmethylcinchonidinium hexafluorophosphateC34H33PF6N2O[α]D25=-190 (c 0.5, acetone)Source of chirality: (−)-cinchonidine

O(9)-Allyl-N-anthracenylmethylcinchonidinium tetrafluoroborateC37H37BF4N2O[α]D25=-154 (c 0.5, acetone)Source of chirality: (−)-cinchonidine

O(9)-Allyl-N-anthracenylmethylcinchonidinium hexafluorophosphateC37H37PF6N2O[α]D25=-189 (c 0.8, acetone)Source of chirality: (−)-cinchonidine

N-9-Anthracenylmethylcinchoninium tetrafluoroborateC34H33BF4N2O[α]D25=+250 (c 1.0, CHCl3)Source of chirality: (+)-cinchonine

N-9-Anthracenylmethylcinchoninium hexafluorophosphateC34H33PF6N2O[α]D25=+166 (c 0.9, acetone)Source of chirality: (+)-cinchonine

O(9)-Allyl-N-anthracenylmethylcinchoninium tetrafluoroborateC37H37BF4N2O[α]D25=+193 (c 0.7, CHCl3)Source of chirality: (+)-cinchonine

O(9)-Allyl-N-anthracenylmethylcinchoninium hexafluorophosphateC37H37PF6N2O[α]D25=+152 (c 0.7, acetone)Source of chirality: (+)-cinchonine