Organocatalytic asymmetric syntheses of functionalized tetrahydropyridazines

Four tetrahydropyridazines, respectively, substituted at the C-3 position with hydroxymethyl, a silyloxymethyl, a carboxylic acid, and a methyl ester have been prepared in good yields and high enantiomeric purities using organocatalytic α-amination of aldehydes as the key step. These compounds have then been tested as organocatalysts for the same reaction.

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(R)-2-(N,N′-Di-tert-butoxycarbonylhydrazino) 5′,5′-dimethoxypentanolC17H34N2O7Ee 97%[α]D25=-4 (c 1.1, MeOH)Source of chirality: enantioselective synthesisAbsolute configuration: (R)

(R)-1-tert-Butyldiphenylsilyl-2-(N,N′-di-tert-butoxycarbonylhydrazino) 5′,5′-dimethoxypentanolC33H52N2O7SiEe 97%[α]D25=+11 (c 1.2, MeOH)Source of chirality: enantioselective synthesisAbsolute configuration: (R)

(R)-3-((tert-Butyldiphenylsilyloxy) methyl)-2,3,4,5-tetrahydropyridazineC21H28N2OSiEe 97%[α]D25=-13 (c 1.2, MeOH)Source of chirality: enantioselective synthesisAbsolute configuration: (R)

(R)-3-Hydroxymethyl-2,3,4,5-tetrahydropyridazineC5H10N2OEe 97%[α]D25=-127 (c 1.0, MeOH)Source of chirality: enantioselective synthesisAbsolute configuration: (R)

(R)-Methyl 2-(N,N′-di-tert-butoxycarbonylhydrazino) 5′,5′-dimethoxypentanoateC18H34N2O8Ee 97%[α]D25=+26 (c 1.0, MeOH)Source of chirality: enantioselective synthesisAbsolute configuration: (R)

(R)-2,3,4,5-tetrahydropyridazine-3-carboxylic acidC5H8N2O2Ee 97%[α]D25=-59 (c 1.0, MeOH)Source of chirality: enantioselective synthesisAbsolute configuration: (R)

(R)-Methyl 2,3,4,5-tetrahydropyridazine-3-carboxylateC6H10N2O2Ee 97%[α]D25=-67 (c 0.9, MeOH)Source of chirality: enantioselective synthesisAbsolute configuration: (R)