Dihydro-1,4-thiazine 1-oxides

The X-ray structures of two derivatives of 3,6-dihydro- 1,2-thiazine 1-oxide 137 indicate (cf. Scheme 51) (02AX165, 02AX198) the six-membered ring to be a half-chair conformer with the S=0 bond in an quasi-axial position. 

The preparation of 3,6-dihydro-1,2-thiazine 1-oxides by [4 + 2] cycloaddition of iV-sulfinyl compounds has been intensively studied since the mid-1980s . The [4 + 2] cycloaddition of iV-sulfinylaniline with 1,3-dienes was first reported in 1953. Since then, a number of Diels-Alder cycloadditions of iV-sulfinyl compounds and the related sulfur diimides have been reported. These cycloadditions usually proceed expeditiously, often exothermically, at... 

Diene synthesis with thionylimines 3,6-Dihydro- 1,2-thiazine 1 -oxides... 

Oxidation o f Dihydro thiazines and Dihydro thiazine Oxides... 

H-1,2-Thiazine 3,6-Dimethyl-l-(4-methyl-benzolsulfonyl)-3,6-dihydro- -1-oxid E21e, 5065 (1,3-Dien + R-S02-NSO)... 

Complete chirality transfer has been achieved in syntheses of 1-amino-2-hydroxy-3-alkenyl derivatives from (Z)-/ -substituted ally] sulfoxides, due to 1,3-allylic strain as an additional controlling factor. Stereochemically homogeneous 3,6-dihydro-l,2-thiazine oxides are easily obtained by hetero Diels-Alder reaction of A-sulfinyl carbamates and ( , )-2,4-hexadienes37 (see Section D.1.6.1.1.1.1.2.2). 

Similarly, the carbamate 400 was treated with thionyl chloride. Dihydro-thiazine S-oxide 403 was produced as an inseparable mixture (15 1) of sulfur... 

Peracids are the normal reagents for effecting the conversions of dihydro-thiazines and their oxides into dihydrothiazine dioxides. Thus the compound 82 was transformed into the sulfone 248 by peracetic acid61 and the sulfoxide 219 afforded the derivative 249 when treated with ro-chloroperbenzoic acid.95 Unpublished studies, performed in the author s laboratory, have shown that compounds of type 199 are readily converted into the sulfones 250 by m-chloroperbenzoic acid.24 In one instance, oxygen has been reported to act... 

The sulfur atom of both 3,6-dihydrothiazine oxides and 3,6-dihydro thiazine imines is readily attacked by nucleophiles other than water or hydroxide ion. Wucherpfennig has reported the cleavage of dihy-drothiazine oxides and dihydrothiazine imines with methoxide ion to afford sulfinate esters or imidosulfinate esters [Eq. (22)].54... 

Oxidation of diethyl 3-methyl-6-oxo-2//,6//-pyrido[2,l-Z)][l,3]thiazine-4,9-dicarboxylate and its 7,8-dihydro derivative with CF3CO3H in CH2CI2 at room temperature gave the respective sulfone in 73% and 38% yields, respectively (99JCS(P1)3569). Sulfoxide 91 or sulfone 92 of... 

Oxidation of 8-(l-methylethenyl)-2-oxo-7-thia-l-azabicyclo[4.3.0]octa-3,5-diene-5,8-dicarboxylate and its 3,4-dihydro derivative with peracids gave diethyl 3-methyl-6-oxo-2/7,6/7-pyrido[2,l- ][l,3]thiazine-4,9-dicarboxylate and its 7,8-dihy-dro derivative, respectively < 1999J(PI)3569>. Reaction of NH2(CH2)3NH2 with 5-O-methanesulfonyl-L-gulofuranose... 

Four regioisomeric dihydrothiazine 1,1-dioxides are possible depending upon the position of the double bond. The most common examples of this subclass include 5,6-dihydro-4//-l,2-thiazine 1,1-dioxides 5, 3,4-dihydro-2//-l,2-thiazine 1,1-dioxides 6, and 3,6-dihydro-2//-l,2-thiazine 1,1-dioxides 7. Scant interest has been paid to 5,6-dihy-dro-2/7-l,2-thiazine 1,1-dioxides 8 or their substituted derivatives. Related 3,6-dihydro-2//-l,2-thiazine 1-oxides 9 are also an important subclass of compounds due to their ease of preparation via [4-f2] cycloaddition reactions. 

Conversion of 3,6-dihydro-277-l,2-thiazine 1-oxides 91 to 677-1,2-thiazines 92 takes place in the presence of the dehydrating agent polyphosphoric acid trimethylsilyl ester (PPSE) (Equation 5) <2001TL4183>. 

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>. 

It is also possible to intercept the chiral sulfoxide intermediate and convert this species to an a-amino ester. Thus, the Grignard addition to dihydro-l,2-thiazine 1-oxides 131a and 131b followed by NH4CI workup and subsequent ozonolysis of 132a and 132b affords amino ester 133 with excellent retention of the absolute stereochemistry (Scheme 17) <2004JOC7198>. 

A -(2,3>5-Trichloro-4-oxocyclohexa-2,5-dienylidene)benzenesulfonamide oxidations of 5,6-dihydro-l,3-thiazines 24 afford excellent yields of l-(4-ethoxy-2,6-diaryl-277-l,3-thiazin-5-yl)ethanone 58 and 59 (Equation 6) <2000CHE862>. 

Theoretical methods have been used to undetstand and predict charge densities and oxidation potentials, nuclear magnetic resonance (NMR) shifts and cycloconjugation in 1,4-thiazines, and the lowest-energy conformation in a dihydro-1,4-thiazine. 

The formation of thiazine systems by ring contractions of 2,3-dihydro-l,4-thiazepine 303 (Equation 108) <1971CC698>, 2,3>4,7-tetrahydro-l,4,5-thiadiazepin-3-one 3, 3 -dioxide 304 (Equation 109) <1972T2307>, 2,3-dihy-drobenzo[ ][l,4]thiazepin-4(57/)-ones 305 and 306 (Scheme 78) <1992LA403>, and 6,7-dihydro-1,4-thiazepin-5(477)-one. -oxide 307 (Equation 110) <1999H(51)1639> has been published. 

The 5,6-dihydro-2/T- and-AH- 1,2-oxazines and -thiazines are interrelated by prototropy, being enamines and imines respectively. In the case of the oxazines the imine form is favoured and there are several well-established examples of this system, including the parent heterocycle (18). This compound is obtained by oxidation of tetrahydro-l,2-oxazine with lead tetraacetate and, although it is reasonably stable, on standing it slowly trimerizes (Scheme 4) (72JCS(Pl)170l). 

Simple alkyl-substituted dihydro-1,4-thiazines are readily converted into the corresponding 5-monoxides atmospheric oxidation is sometimes sufficient, although side reactions may also occur. The cyclohexene derivative (99), for instance, affords not only the oxide (100) but also the spiro compound (101) probably generated by ring contraction of a hydroperoxide intermediate (Scheme 42) <73US(B)(8)34l>. 

Hydrogen peroxide converts morpholine into its 4-hydroxy derivative (50JA2280), but TV-alkyl morpholines yield 3-oxo compounds if ruthenium(VIII) oxide or sodium metaperiodate are used as oxidants (76S598). Chlorine at -70 °C oxidizes the thiomorpholine (116) to the dihydro-1,4-thiazine (117) (73JCS(Pl)l32l), but more vigorous conditions result in the formation of S-oxides. 

Dihydro-1,4-thiazine 1-oxides or 1,1-dioxides can be made from the parent heterocycles by oxidation, or from alkynylcysteine 1-oxides or 1,1-dioxides by treatment with aqueous ammonia (Scheme 121) (71JOC611). 

H,3H-Oxazolo[4,3-c][l,4]thiazine-6-carboxylic acid 7-oxide, 8,8a-dihydro-3,3-dimethyl-, methyl ester X-ray, 6, 647 <74JCS(P2)1132)... 

Dihydrobenzo-TAs 164 may be obtained from compounds containing a 1,3-thiazine ring, for example, by oxidation of 2,3-dihydro-l,3-benzothiazine-4-thiones (55BSF1518) (Scheme 56). The reduction of 1,3-benzo-TA, affording 2,3-dihydro derivatives, is described in Section III,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. 

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