1.2- Benzothiazines, fused systems

In the discussions, the syntheses, stereochemistry, and transformations of cycloalkane d -fused and e -fused systems are described in parallel these correspond to 3,1-benzoxazines and 3,1-benzothiazines, and to 1,3-benzoxazines and 1,3-benzothiazines, respectively. The syntheses are frequently similar, but totally different methods are often used for the d -fused and e -fused heterocycles. The main syntheses (A-J) of the ring systems discussed in this review are given in Fig. 1. 

A logical extension of the synthetic strategy underlying our solid-phase approach toward 1,5-benzothiazepinones was to replace the [3-mercapto acids (cysteine, penicillamine) by a-mercapto acids, such as mercaptoacetic acid 54a or thiolactic acid 54b. This change would facilitate access to the corresponding [6,6]-fused systems, i, e. 1,4-benzothiazin-3-ones 57. As with the benzothiazepines, no solid-phase synthesis of benzothiazines has been reported to date. 

One of the most commonly encountered applications of Smiles rearrangements in synthesis is to prepare fused aromatic systems via three-step cascades displaying two nucleophilic substitutions with a Smiles rearrangement in between. These sequences have been adapted into more conplex three-conponent couplings such as the benzothiazine synthesis shown in Scheme 19.9. hi this process, 19 reacts first with acyl chloride 18 leading to 20 after substitution with 17. Heating the mixture under microwave conditions tri ers the Smiles rearrangement and the final Sj Ar toward 21. 

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