Cycloadditions with Alkoxynitrile Oxides, RO--C=N(+)--O(-), (Alkyl Cyanate N-Oxides).

Abstract

Alkyl formhydroximates have been synthesized by reacting alkyl orthoesters with hydrogen sulfide followed by treatment of the alkyl thioformate formed with hydroxylamine. Chlorination of alkyl formhydroximates with N-chlorosuccinimide gives alkyl chloroformhydroximates and dehydrochlorination with base generated alkoxynitrile oxides (alkyl cyanate N-oxides), which efficiently undergo cycloaddition to olefins or acetylenes to give 3-alkoxyisoxazolines or 3-alkoxyisoxazoles, respectively. These compounds are masked beta-hydroxy- and beta-keto-esters. Reductive cleavage of the ring was performed by hydrogenation over Raney-Ni or with Ti3+ salts. The reaction thus constitutes a novel hydroxycarboxylation. DL-N-Boc-gamma-amino-beta-hydroxybutyrates (Gabob), mevalonic acid, citromalic acid, malic acid derivatives and N-methyl-N-hydroxythioformamide (thioformin) have been synthesized. N,N-Dimethyl-N'-hydroxychloroformamidine (N,N-dimethylaminochloroform oxime) was not formed by chlorination of N,N-dimethyl-N'-hydroxyformamidine. The nitrile oxide cycloaddition to cycloheptatriene was investigated. The [6 + 4] cycloaddition mode was not observed but three isomeric [4 + 2] cycloaddition products were isolated and structurally determined.