During the present research the synthesis of β-keto-γ-sultams from α-amino acids was for the first time accomplished at room temperature and applied to obtaining spirocyclic compounds. The first 2,3,3,5-tetrasubstituted β-keto-γ-sultam was also obtained by direct cyclization. Moreover, affordable, reliable and scalable synthetic approaches to 1-aminocyclopropane- and 1-aminocyclobutanecarboxylic acids were elaborated.
The first systematic study of the chemical properties of 2,3,3-trisubstituted 1λ6-isothiazolidine-1,1,4-triones was conducted, including exploration of the effect of spirocyclic substituents at the C(3) position on the reactivity of the carbonyl and active methylene groups of the heterocycles.
The reactivities of 2,3,3-trimethyl- and 2-methyl-3-spirocyclo-substituted 1λ6-isothiazolidine-1,1,4-trionestowards a range of nucleophilic and electrophilic reagents were compared. As a result, first 2,3,3-trimethyl- and 2-methyl-3-spirocyclo-substituted 1,1-isothiazolidinedione-4-hydrazones and-oximes, 4-ethoxycarbonylmethylidene-1,1-isothiazolidinediones, 4-pyrrolidinyl- and 4-anilino-2,3-dihydro-1H-1λ6-isothiazole-1,1-diones, 5,5-dimethyl-, 5-benzoyl-1,1,4-isothiazolidinthriones, 1,1,4-isothiazolidinthrione-5 -carboxamides, -5-carbothioamides, -5-hydrazones, as well as 2,3,3-trimethyl-substituted 4-chloro-1,1-dioxo-2,3-dihydro-1H-1λ6-isothiazole-5-carbaldehyde, 1λ6-isothiazolidine-1,1,4,5-tetron-5-oxime and 2-methyl-3-spirocyclopropyl-substituted 5-ethoxy-methylidene-, 5-phenylmethylidene-, 1,1,4-isothiazolidine and a set of 2-methyl-3-spirocyclo-substituted 5-dimethylaminomethylidene-1,1,4-isothiazolidinetriones were obtained. The first acylation of α-methylene active ketone with Wittig's reagent to yield previously unknown 2,3,3-trimethyl-1,1-dioxo-5-[2-(triphenylphosphonio)acetyl]-2,3-dihydro-1H-1λ6-isothiazole-4-olate is described.
The first reduction of the carbonyl group of 1λ6-isothiazolidine-1,1,4-triones to the hydroxyl group is reported.
