Reaction of Aroylpyrrolobenzothiazinetriones with Electron‐Rich Dienophiles

Abstract

The development of synthetic protocols to small molecules with a complex 3D shape is a relevant problem for modern chemists because such molecules are required by drug discovery. The Diels-Alder reaction is a good synthetic approach to complex three-dimensional structures. In the present paper, a reaction of aroylpyrrolobenzothiazinetriones (oxa-dienes) with electron-rich dienophiles is investigated in order to reach novel alkaloid-like pyrano [4,3-b]pyrroles fused to a 1,4-benzothiazine-2-one moiety. The studied reaction was found to proceed highly regioselectively. Its stereoselectivity was dramatically dependent on the reaction solvent. The experimental results are supplemented with computational studies, which demonstrate that the studied reaction proceeds via a one-step polar mechanism. In addition, an improved synthesis of alkaloid-like pentacyclic 6/6/5/6/5-and 6/6/5/6/6angularly fused pyrano [4,3-b]pyrroles via an acid-catalyzed intramolecular cyclization of Michael adducts to hetero-Diels-Alder cycloadducts was discovered. The synthesized alkaloidlike heterocycles represent an interest to pharmaceutics, since their close analogs show significant antiviral activity.

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

“…It should be noted that the reactions of 5-aza- and 5-oxa-FPDs I and II with nucleophiles are studied rather well [ 33 – 34 ], and their reactivity did not give us any insights for the development of new approaches to PBTAs. However, recently, we have reported a new class of FPDs, aroylpyrrolobenzothiazinetriones (APBTTs) 1 ( Figure 2 ) [ 37 – 38 ], whose structural features allowed us to assume a possibility of the development of a new approach to PBTAs via a nucleophile-induced ring contraction in the 1,4-benzothiazine moiety of compounds 1 ( Scheme 5 ). Firstly, FPDs 1 bear a 1,4-benzothiazine moiety that is known to be prone to undergo a ring contraction reaction to afford the corresponding 1,3-benzothiazole derivatives under the action of nucleophiles [ 39 – 42 ], oxidizing agents [ 43 – 48 ] or ultraviolet irradiation [ 49 ].…”

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

“…FPDs are highly reactive compounds [25,26] containing an highly electrophilic enone fragment which facilitates the course of cycloaddition and nucleophilic addition reactions. In recent years, some types of cycloaddition reactions were investigated for FPDs: the [4 + 2] cycloaddition with alkenes resulting in pyran-annulated products [27][28][29][30][31][32][33][34] and the [3 + 2] cycloaddition with nitrones resulting in isoxazole-annulated products [35][36][37] (Scheme 2). However, formal [4 + 1] cycloaddition reactions for FPDs remain to be unknown.…”

Approach to Pyrido[2,1-b][1,3]benzothiazol-1-ones via In Situ Generation of Acyl(1,3-benzothiazol-2-yl)ketenes by Thermolysis of Pyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones

“…Recently, we have reported [ 10 ] a new type of FPDs, 3-aroylpyrrolo [2,1- c ][1,4]benzothiazine-1,2,4-triones (APBTTs) 1 , prone to undergo a 1,4-thiazine ring contraction reaction to afford corresponding 1,3-thiazole derivatives under certain conditions [ 11 ]. These seem to be a promising feature for the development of a synthetic strategy to pyrido [2,1- b ][1,3]benzothiazol-1-ones through chemical transformations of APBTTs 1 .…”