One-pot synthesis of methyl 4-amino-2,3,3-trisubstituted-1,1-dioxo-2,3-dihydro-1H-1λ6-isothiazole-5-carboxylates

A Study on Sulfonylation of Cyanohydrins with α‐Functionalized Sulfonyl Chlorides

“…Thus, the enamine fragment along with attached EWG (either CO 2 Me in 1 or CN in 2 ) form the conjugated system with delocalized lone pair and π electrons across the adjacent aligned p orbitals. This assumption was supported by previously conducted X‐ray diffraction study of congener β‐enamino γ‐sultam possessing methyl carboxylate group at the same α‐position [8] . This type of compounds are also characterized by two separate singlets of amino group in 1 H NMR spectrum and by downfield shifts of C=C moiety of enamine fragment in a similar range of 13 C NMR spectrum.…”

“…This assumption was supported by previously conducted X-ray diffraction study of congener β-enamino γ-sultam possessing methyl carboxylate group at the same α-position. [8] This type of compounds are also characterized by two separate singlets of amino group in 1 H NMR spectrum and by downfield shifts of C=C moiety of enamine fragment in a similar range of 13 C NMR spectrum. On the other hand, the steric hindrance in 3 and 4 caused by repulsive interaction between the amino group of sultone framework and the annular atoms of the phenyl substituent pushes the latter out of the sultone ring plane eventually hampering the conjugation between them (Figure 3).…”

Updating the CSIC Reaction (2003–2020)

“…Thus, aminonitriles 23 a-d and 39 a-h when treated with methyl 2-(chlorosulfonyl) acetate 40 turned into interim sulfonamides 41 which bypassing the isolation step were converted into appropriately substituted methyl 4-amino-1,1-dioxo-2,3-dihydro-1H-1λ 6 -isothiazole-5-carboxylates 42 a-l without utilization of another stronger base (Scheme 13). [33] This is also true for α,α-disubstituted cyanohydrins. Sulfonylation of 43 a-g with methyl 2-(chlorosulfonyl)acetate 40 under the above conditions resulted in "one-pot" formation of the corresponding 5,5-disubstituted and spirocyclic methyl 4amino-2,2-dioxo-2,5-dihydro-1,2λ 6 -oxathiole-3-carboxylates 45 a-g (Scheme 14).…”

“…Thus, aminonitriles 23 a – d and 39 a – h when treated with methyl 2‐(chlorosulfonyl)acetate 40 turned into interim sulfonamides 41 which bypassing the isolation step were converted into appropriately substituted methyl 4‐amino‐1,1‐dioxo‐2,3‐dihydro‐1 H ‐1λ 6 ‐isothiazole‐5‐carboxylates 42 a – l without utilization of another stronger base (Scheme 13). [33] …”

Synthesis of Spirocyclic β‐ and γ‐Sultams by One‐Pot Reductive Cyclization of Cyanoalkylsulfonyl Fluorides

“…Most of these methods have been used for the synthesis of monocyclic and fused bicyclic γ‐sultams. While the preparation of γ‐sultams bearing a spirocyclic fragment at the C‐5 position has also been presented in the literature, [46–50] their C‐4‐substituted counterparts are underrepresented to date, being limited by several 4,4'‐spirobi(γ‐sultam) derivatives [51] . Keeping in mind further possible applications in lead discovery projects, herein we have aimed at preparation of spirocyclic building blocks 1a – h (Figure 1) with high sp 3 ‐atom fraction bearing alicyclic or saturated heterocyclic moieties at the C‐4 position of the sultam ring.…”