Highly chemoselective reactions on hindered sulfamidates with oxygenated nucleophiles

Although the chemoselectivity problems in substitution reactions, which arise from the use of oxygenated nucleophiles in a basic medium by generating anionic species are well-known, we report herein a highly chemoselective ring-opening reaction of hindered cyclic sulfamidates with O-nucleophiles. The reaction occurs with the inversion of configuration at the quaternary centre, allowing the stereoselective synthesis of an important class of β2,2-amino acids, namely O-substituted α-methylisoserines.

Figure optionsDownload as PowerPoint slide

Methyl 5-hydroxycarbonyl-5-methyl-2,2-dioxo-2λ6-[1,2,3]oxathiazolidine-3-carboxylateC6H9NO7SEe > 93%[α]D25=-4.3 (c 1.30, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

2-Methoxycarbonylaminomethyl-2-(p-nitrobenzoyloxy)-N-methoxy-N-methylpropanamideC15H19N3O8Ee > 93%[α]D25=-11.8 (c 0.94, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

5-Methyl-5-(N-methoxy-N-methylcarbamoyl)-2,2-dioxo-2λ6-[1,2,3]oxathiazolidineC6H12N2O5SEe > 93%[α]D25=-46.3 (c 1.04, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

Methyl 5-methyl-2,2-dioxo-2λ6-[1,2,3]oxathiazolidine-5-carboxylateC5H9NO5SEe > 93%[α]D25=-24.4 (c 1.30, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

5-Methyl-2,2-dioxo-2λ6-[1,2,3]oxathiazolidine-5-carboxylic acidC4H7NO5SEe > 93%[α]D25=-8.0 (c 0.99, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

2-Methoxycarbonylaminomethyl-2- phenyloxy-N-methoxy-N-methylpropanamideC14H20N2O5Ee > 93%[α]D25=-42.8 (c 1.03, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Methyl 2-methoxycarbonylaminomethyl-2-phenyloxypropanoateC13H17NO5Ee > 93%[α]D25=-6.9 (c 1.88, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

2-Aminomethyl-2-hydroxypropanoic acid or α-MethylisoserineC4H9NO3Ee > 93%[α]D25=-2.6 (c 1.01, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

2-Aminomethyl-2-phenyloxypropanoic acid hydrochloride or O-Phenyl-α-methylisoserineC10H14ClNO3Ee > 93%[α]D25=-16.8 (c 1.38, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

N-(Tosyl)phenylalaninyl-O-phenyl-α-methylisoserine methyl esterC27H30N2O6SEe > 93%[α]D25=-35.8 (c 1.38, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)