Preparation of novel N-sulfonylated (S,S)-2,3-diaminosuccinate-type chiral auxiliaries and application to an asymmetric 1,3-dipolar cycloaddition reaction of nitrile oxides to allyl alcohol

Novel N-sulfonylated (S,S)-2,3-diaminosuccinate-type chiral auxiliaries, which have the tartaric acid-like framework with a sulfonamide group instead of a hydroxyl group, were synthesized from l-aspartic acid. The synthesized (S,S)-2,3-diaminosuccinate derivatives were applied to an asymmetric 1,3-dipolar cycloaddition reaction of nitrile oxides to allyl alcohol to afford the corresponding optically active 2-isoxazolines, with the enantioselectivities of up to 73% ee. The enantiofacial differentiation was intriguingly opposite to that by using diisopropyl tartrate as a chiral auxiliary.

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Dimethyl (S,S)-2,3-bis(4-methylphenylsulfonamido)succinateC20H24N2O8S2Ee = 100%[α]D25=+123 (c 0.23, CHCl3)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Dimethyl (S,S)-2,3-bis(naphthalene-2-sulfonamido)succinateC26H24N2O8S2Ee = 100%[α]D25=+138 (c 0.26, CHCl3)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Dimethyl (S,S)-2,3-bis(naphthalene-1-sulfonamido)succinateC26H24N2O8S2Ee = 100%[α]D25=+146 (c 0.23, CHCl3)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Dimethyl (S,S)-2,3-bis(2,4,6-trimethylphenylsulfonamido)succinateC24H32N2O8S2Ee = 100%[α]D25=+81 (c 0.31, CHCl3)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Dimethyl (S,S)-2,3-di(methylsulfonamido)succinateC8H16N2O8S2Ee = 100%[α]D25=+32 (c 0.2, CHCl3)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Dimethyl (S,S)-2,3-bis(trifluoromethylsulfonamido)succinateC8H10N2O8F6S2Ee = 100%[α]D25=+26 (c 0.22, EtOH)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Diisopropyl (S,S)-2,3-bis(4-methylphenylsulfonamido)succinateC24H32N2O8S2Ee = 100%[α]D25=+63 (c 0.15, EtOH)Source of Chirality: l-aspartic acidAbsolute configuration: (S,S)

Di-tert-butyl (S,S)-2,3-bis(4-methylphenylsulfonamido)succinateC26H36N2O8S2Ee = 100%[α]D25=+103 (c 0.21, CHCl3)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Di-tert-butyl (S,S)-2,3-bis(naphthalene-2-sulfonamido)succinateC32H36N2O8S2Ee = 100%[α]D25=+131 (c 0.2, CHCl3)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Di-tert-butyl (S,S)-2,3-bis(naphthalene-1-sulfonamido)succinateC32H36N2O8S2Ee = 100%[α]D25=+104 (c 0.2, EtOH)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Di-tert-butyl (S,S)-2,3-bis(2,4,6-trimethylphenylsulfonamido)succinateC30H44N2O8S2Ee = 100%[α]D25=+89 (c 0.24, CHCl3)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Di-tert-butyl (S,S)-2,3- di(methylsulfonamido)succinateC14H28N2O8S2Ee = 100%[α]D25=-5 (c 0.2, CHCl3)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

Di-tert-butyl (S,S)-2,3-bis(trifluoromethylsulfonamido)succinateC14H22N2O8F6S2Ee = 100%[α]D25=+10 (c 0.22, CHCl3)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

(R)-5-(Hydroxymethyl)-3-(4-methoxyphenyl)-2-isoxazolineC11H13NO3Ee = 71%[α]D25=-94 (c 0.53, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-5-(Hydroxymethyl)-3-(4-bromophenyl)-2-isoxazolineC10H10NO2BrEe = 57%[α]D25=-61 (c 0.29, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-5-(Hydroxymethyl)-3-(4-cyanophenyl)-2-isoxazolineC11H10N2O2Ee = 49%[α]D25=-75 (c 0.22, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)