Synthesis of carbo- and heterofused 5-amino-2H-1,2-thiazine 1,1-dioxides via the CSIC reaction strategy

• Published in: Tetrahedron Vol. 109; p. 132685
• Main Authors: Dyachenko, Maksim S., Chuchvera, Yaroslav O., Dobrydnev, Alexey V., Frolov, Andriy I., Ostapchuk, Eugeniy N., Popova, Maria V., Volovenko, Yulian M.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 12-03-2022
• Subjects: Aminonitriles; Cyclization; Enamines; Heterocycles; Sulfonamides; Aminonitriles; Heterocycles; Cyclization; Sulfonamides; Enamines
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2022.132685

Herein, we present a full account of our studies with respect to the synthesis of carbo- and heterofused β-enamino-δ-sultams annelated on face c (3,4-bond). This class of compounds was designed as isomeric counterpart of known pharmacological templates – fused δ-sultams annelated through a face e (5,6-bond) following the principles of bioisosteric replacement. The starting material for this synthesis is cyclic vicinal amino nitriles. In particular, several methods were developed for methanesulfonylation of 5- and 6-membered carbo- and heteroaromatic as well as sp3-enriched β-enamino nitriles depending on their chemical nature and reactivity. The obtained N-mono- or/and N,N-dimesylates were converted into the corresponding N-methylmethanesulfonamides, which were subjected to the CSIC (Carbanion-mediated Sulfonate (Sulfonamide) Intramolecular Cyclization) reaction protocols thus affording target carbo- and heterofused β-enamino-δ-sultams. Their synthetic utility was demonstrated by the reactions with carbo- and hetero electrophiles.
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