Regioselective construction of six-membered fused heterocyclic rings via Pd/C-mediated C-C coupling followed by iodocyclization strategy:: a new entry to 2H-1,2-benzothiazine-1,1-dioxides

We describe a practical and elegant method of constructing a thiazine ring fused with benzene under mild reaction conditions. A variety of 4-iodo-2H-benzo[e] [ 1,2]thiazine-1,1-dioxides were prepared with high regioselectivity via a two-step process involving Pd/ C-mediated C-C coupling of o-halobenzenesulfonamides with terminal alkynes, followed by iodocyclization of the resulting o-(1-alkynyl)-arenesulfonamide using elemental iodine in acetonitrile. The coupling reaction was carried out using 10% Pd/C-PPh3-CuI as a catalyst system in the presence of Et3N. The process worked well for bromides and iodides, and a wide array of terminal alkynes containing alkyl and aryl substituents were employed. The iodocyclization step tolerated a variety of functional groups such as hydroxy, chloro, cyano, and methoxy, producing the six-membered heterocyclic ring selectively. The resulting 4-iodo-2H-benzo[e] [ 1,2]thiazine-1,1-dioxides participated in Sono-gashira, Heck, and Suzuki reactions producing a wide range of functionally substituted benzothiazines in good yields. (c) 2007 Elsevier Ltd. All rights reserved.