Synthesis of Functionalized 4,1‐Benzothiazepines via a [4+3] Annulation between Aza‐o‐Quinone Methides and Pyridinium 1,4‐Zwitterionic Thiolates

Abstract

The [4 + 3] annulation of aza-o-quinone methides and pyridinium 1,4-zwitterionic thiolates has been developed for the one-step synthesis of functionalized 2,3-unsaturated 4,1-benzothiazepines under mild and metal-free conditions. The produced 4,1-benzothiazepines can easily be converted into biologically interesting sulfoxides and sulfones via selective oxidization with m-CPBA.

Recent Progress in Heterocycle Synthesis: Cyclization Reaction with Pyridinium and Quinolinium 1,4-Zwitterions

“…In 2021, both Chen et al and Wang et al independently implemented (3 + 4) cycloaddition reactions between aza- o -quinone methides 57 (in situ generated from 55 ) and pyridinium 1,4-zwitterions 1 ( Scheme 14 , top) [ 73 , 74 ]. Chen et al selected K 2 CO 3 as the optimal base to promote the reaction, and the reaction yielded functionalized benzo[ e ][1,4]thiazepines 56 in 57–99% yields [ 73 ].…”

Synthesis of aryl-fused 1,4-oxathiepines from pyridinium 1,4-zwitterionic thiolates and vinylideneortho-quinone methides

“…, arynes, alkynes, allenes, α-functionalized bromoalkanes, and α-halo hydrazones, among others) to access various heterocycles via diverse reaction modes. 3 Among them, the pyridine moiety of a thiolate can not only be used as a leaving group but can also be incorporated into the products. For example, it reacted with α-bromo hydrazones to afford 2,5-dihydro-1,4,5-thiadiazepines in high yields in the presence of Na 2 CO 3 via the (3 + 4) pathway (Scheme 1).…”

“…11 To the best of our knowledge, there were no other reports on the reactions between α-alkynylnaphthalen-2-ols and zwitterionic substrates (or zwitterionic equivalents generated in situ ). Given our continuous interest in sulfur chemistry, 12 especially that of pyridinium 1,4-zwitterionic thiolates, 3 we envisioned whether they could react with in situ generated VQMs from ortho -alkynyl aromatic phenols to give aryl-fused 1,4-oxathiepines via the (3 + 4) mode. Besides, VQMs produced from 2-alkynylphenols have never been successfully produced in high yields so far.…”

Copper-Catalyzed Decarboxylative Cascade Cyclization of Propargylic Cyclic Carbonates/Carbamates with Pyridinium 1,4-Zwitterionic Thiolates to Fused Polyheterocyclic Structures

“…Despite these advances, the application of the compounds 1 for the preparation of fused polyheterocyclic compounds has not been disclosed yet in the literatures. In addition, we noticed that the synthesis of 1,4-zwitterionic thiolates 2 was reported by Bazgir as early as 2011, but until recently, employing them as a kind of versatile sulfur-containing building synthons for a wide array of cycloaddition reactions to access various heterocycles was documented mainly from Zhai’s group and others . To the best of our knowledge, the possible reaction between compounds 1 and 2 still remains unexplored.…”