Resolution of 1-arylalkylamines with 3-O-hydrogen phthalate glucofuranose derivatives: role of steric bulk in a family of resolving agents

The development of three new acidic resolving agents which are hydrogen phthalates of 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose 1, 1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranose 2 and 1,2-O-cyclohexylidene-5,6-O-diphenylmethylidene-α-d-glucofuranose 3 is shown for the resolution of 1-arylalkylamines 7a–k. The salts between 1, 2 and (RS)-1-arylalkylamines 7a–k selectively crystallize 1·(S) 7a–j and 2·(S) 7a–h salts, allowing us to recover the corresponding bases (S) 7a–j and (S) 7a–h, respectively, in good yield and enantiomeric excess (73–95% ee). Whereas, the salts between 3 and (RS)-1-arylalkylamines 7a–c,g–i,k selectively crystallize 3·(S)-7a–c,g–i salts to recover the corresponding bases (S)-7a–c,g–i in poor enantiomeric excess (4–35% ee). The difference between the resolving ability of 1 and 2 for 1-arylalkylamines 7a–h is very slight, but there is considerable difference compared to ortho-substituted 1-arylalkylamines 7i and 7j. The role of substituents on a family of resolving agents 1, 2 and 3 is also discussed to interpret their resolving ability.

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3-(1,2:5,6-Di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC20H24O9[α]D = −9.5 (c 1.0, EtOH)Source of chirality: d-glucose

3-(1,2:5,6-Di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC26H32O9[α]D = −7.2 (c 1.0, EtOH)Source of chirality: d-glucose

3-(1,2-O-Cyclohexylidene-5,6-O-diphenylmethylidene-α-d-glucofuranosyl)-hydrogen phthalateC33H32O9[α]D = −43.2 (c 1.0, MeOH)Source of chirality: d-glucose

1,2-O-Cyclohexylidene-5,6-O-diphenylmethylidene-α-d-glucofuranoseC25H28O6[α]D = +30.8 (c 1.0, MeOH)Source of chirality: d-glucose

(S)-1-Phenylethylammonium 3-(1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC28H35NO9[α]D = −42.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-Phenylethylammonium 3-(1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC29H37NO9[α]D = −24.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(4-Chlorophenyl)ethylammonium 3-(1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC28H34ClNO9[α]D = −31.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(4-Ethylphenyl)ethylammonium 3-(1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC30H39NO9[α]D = −43.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(4-Bromophenyl)ethylammonium 3-(1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC28H34BrNO9[α]D = −35.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(4-Methoxphenyl)ethylammonium 3-(1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC29H37NO10[α]D = −43.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(4-Methylphenyl)ethylammonium 3-(1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC29H37NO9[α]D = −34.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(3-Methoxyphenyl)ethylammonium 3-(1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC29H37NO10[α]D = −33.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(2-Chlorophenyl)ethylammonium 3-(1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC28H34ClNO9[α]D = −45.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(2-Methoxyphenyl)ethylammonium 3-(1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl)-hydrogen phthalateC29H37NO10[α]D = −92.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-Phenylethylammonium 3-(1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranosyl)-hydrogen phthalateC35H47NO9[α]D = −40.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-Phenylethylammonium 3-(1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranosyl)-hydrogen phthalateC36H49NO9[α]D = −27.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(4-Chlorophenyl)ethylammonium 3-(1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranosyl)-hydrogen phthalateC35H46ClNO9[α]D = −35.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(4-Ethylphenyl)ethylammonium 3-(1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranosyl)-hydrogen phthalateC37H51NO9[α]D = −29.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(4-Bromophenyl)ethylammonium 3-(1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranosyl)-hydrogen phthalateC35H46BrNO9[α]D = −35.0(c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(4-Methoxyphenyl)ethylammonium 3-(1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranosyl)-hydrogen phthalateC36H49NO10[α]D = −38.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(4-Methylphenyl)ethylammonium 3-(1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranosyl)-hydrogen phthalateC36H49NO9[α]D = −40.0 (c 1.0, EtOH)Source of chirality: d-glucose

(S)-1-(3-Methoxyphenyl)ethylammonium 3-(1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranosyl)-hydrogen phthalateC36H49NO10[α]D = −33.0 (c 1.0, EtOH)Source of chirality: d-glucose