Thiazine 1-oxides, synthesis

Thiazepinones, as photolytic products 883 Thiazine 1-oxides, synthesis of 323, 352 Thiene dioxides formula of 382 synthesis of 469 Thiene oxides formula of 382 synthesis of 469... 

One notable advance in this chemistry since the publication of CHEC-II(1996) is the use of enantiomerically enriched 3,6-dihydro-l,2-thiazine 1-oxides in the rearrangement sequence. For instance, iV-Cbz-protected bicyclic 1,2-dihydrothiazine 44 undergoes ring opening upon treatment with phenylmagnesium bromide (Scheme 16). The synthesis of allylic amino alcohol 129 is completed in excellent yield upon exposure of the intermediate sulfoxide 130 to trimethyl phosphite and methanol at 80 °C <2002TA2407, 2000TL3743>. 

The most straightforward method for the synthesis of the sulfonamide class of 1,2-thiazines is the intramolecular amidation reaction between a sulfonyl chloride and an amine. Preparation of the sulfonyl chloride moiety via the oxidation of thiol acetate 179 and subsequent deprotection and cyclization afforded sulfonamide 180, an intermediate for the synthesis of the matrix metalloproteinase inhibitor 38 (Scheme 22) <2004JME2981>. 

Oxidative C-H amination has been an area of intensive research since the publication of CHEC-II(1996). This methodology has been applied to the synthesis of a variety of 1,2-thiazine 1,1-dioxides. In the simple cases, substrates containing an aromatic C-H can be cyclized in the presence of hypervalent iodine. For instance, the reaction of A-methoxy(2-arylethane)sulfonamide 202 with [hydroxyl(tosyloxy)iodo]benzene rapidly affords benzenesulfon-amide 203 in excellent yield (Equation 30) <20030BC1342> see also <2000JOC926> and <2000JOC8391>. 

Two syntheses of fully conjugated 5 -methyl-l,4-thiazine j -oxides were included in CHEC(1984) <1965CB3724, 1976H(4)1875>. The new approach (Equation 69) made possible the synthesis of 3-amino-5-aryl derivatives <1986LA1648>. 

For less reactive thiazines sodium periodate or 3-chloroperbenzoic acid are suitable reagents for sulfoxide synthesis but it is not always possible to prevent over-oxidation and the formation of the corresponding sulfone (75JCS(P1)716>. Carbonyl substituents at C-6... 

The hetero-DielsAlder reaction of A-sulfinyl 141 (X = 0 or NR) or thionitrosoarene 144 dienophiles with dienes 142 is the main method for the formation of 3,6-dihydro-2//-l,2-thiazine 1-oxides 143 or 3,6-dihydro-2//-1,2-thiazines 145 (Scheme 73) . The mechanistic and stereochemical aspects of this reaction are covered in detail in GHEC-II . In general, thionitrosoarenes 144 are transient in nature, rather difficult to prepare, and thus have a limited role in the synthesis of 1,2-thiazines. On the other hand, A-sulfinyl compounds 141 and related sulfur diimines are more stable and are isolable species. The common method of preparation of the A-sulfinyl compounds involves treatment of an amine or amide with SOCl2 and base. 

Chlorinated thiazines, synthesis and dehalogenation of 85S586. Dihydrothiazine N-oxides in synthesis of unusual sugars 86BSB1021. Oxo- and thioxo-l,3-thiazines, synthesis and properties 86KGS3. Phenothiazines, IR spectra of 83H(20)283. 

In the former case, the precursors are stable molecules that are readily prepared (Sections V,B and V,C,l,c). The procedure involves the isomerization of the exocyclic double bond at position 3 to an endocyclic location no change in the oxidation level of the system results. Examples of this type include the conversions of the thiones 12a and 12b into the derivatives 13a and 14 by triethyloxonium tetrafluoroborate and methyl iodide, respectively. A further case, resulting in the formation of the only known mono-cyclic 4/7-1,4-thiazine 15, is provided by the reaction of the thiazinium iodide 14 with potassium t-butoxide the derivative 15 is reported to be an unstable red oil. Although its generality has not been tested, the synthesis... 

A very similar process can be used in the synthesis of fully conjugated 1,2-thiazine 1-oxides. Ethoxyalkylidenemalononitriles (152a) or the related dithioacetal (152b), can be reacted with S,S-dimethylsulfoximide (153) to yield Michael adducts (154). These compounds undergo base-induced cyclization to afford 1,2-thiazines (155) <88CB1005>. The ketene dithioacetal (156) reacts with the sulfoximide (153) at 100-150°C to yield the thiazine (157) (Scheme 28) <83S926>. 

A large amount of activity on 1,4-benzodiazepine derivatives was reported in 2004. Tetrahydro-l,4-benzazepin-2-one derivatives are of interest as P-turn peptidomimetics and their solid-phase synthesis was reported by Kim et al. <04JC0207>. The diasteroselective synthesis of two enantiopure tetrahydro-l,4-benzodiazepin-5-ones was also achieved based on intramolecular azide cycloaddition and subsequent stereoselective reduction of the 1,4-benzodiazepinone products <04TA687>. A different approach to tetrahydro-1,4-benzodiazepin-5-ones 80 involves the 1,2-thiazine 1-oxides 77 as key intermediates. These intermediates were then converted to the nitroaryl amides 78 (R , R, R = H or Me) which could be cyclised to 80 after hydrogenation of the nitro group via the intermediates 79 <04T3349>. 

This short review has highlighted the wide range of 1,4-thiazines that occur in Nature. The N,S-heterocycle appears in a number of guises, notably as simple monocyclic di- or tetrahydro derivatives with all possible oxidation levels at sulfur, as benzothiazinones, and as thiazine-S,S-dioxides fused to quinones. The review also shows that many of these interesting heterocyclic compounds are yet to succumb to synthesis, and we hope that the article will stimulate further work in this area. 

---