Dihydrothiazine oxide conformation

Until recently, dihydrothiazine oxides had not found much use in synthesis. Recently, Weinreb and coworkers have exploited some of the known reactions of these adducts, along with some new transformations, in stereoselective preparation of some complex nitrogen-containing molecules. One useful transformation of these adducts is the hydrolysis/retro-ene elimination of sulfur dioxide shown in equation (53). Thus dihydrothiazine oxide (120), prepared from ( , )-tetramethylbutadiene, underwent hydrolysis to allylic sulfinic acid (121) which suffered a retro-ene reaction via the chair-like conformation... 

Another useful reaction of these Diels-Alder adducts is shown in equation (54). Dihydrothiazine oxide (123) from ( . )-2,4-hexadiene can be opened with a Grignard reagent to allylic sulfoxide (124) which undergoes a stereoselective 2,3-sigmatropic rearrangement via the envelope-like transition state conformation shown, having a quasi-equatorial methyl group to afford sulfenate ester (125). Desulfurization of (125) provides E)-threo smino alcohol derivative (126) in excellent overall yield. If ( ,Z)-2,4-hexadiene is used, the E)-erythro epimer of (126) is formed cleanly. 

The conformational properties of dihydrothiazine oxides of types 239 and 242 have been examined by NMR spectroscopy. In the case of the (R)-oxides 239, there is a dramatic preference for the conformer 241 by contrast, the (S)-oxides 242 exist overwhelmingly as the conformer 243. These results illustrate that the conformer that possesses an axial 5-oxide is favored. The eonformer 243 possesses an imfavorable 1,3-diaxial interaction between the oxide group and R, and the conformer 241 is destabilized by an allylic interaction between R and R. Evidently, these interactions are less severe than the allylic interaction between the oxide and methoxy-carbonyl groups which would be present in the conformers 244 and 240. 

The dihydrothiazine oxide (73) gives the (Z)-allylic sulfoxide (77), which (/,/2 = 90 min) is slowly converted to a mixture of ( )-allylic sulfoxides (78) that are epimeric at the sulfur atom. This well-precedented transformation of (77) to the thermodynamically more stable (78) involves conformational inversion of the sulfenate ester (79a) to (79b). At any stage of this equilibrium, treatment with a thiophile such as trimethyl phosphite can stereospecifically lead to the (F -hydroxy carbamate (74) (Scheme 13) <84JA7861>. This versatile transformation has been applied to stereospecific vicinal amino alcohol synthesis. 

The conformational properties of dihydrothiazine dioxides of type 250 have been examined by NMR spectroscopy.24 In general, N-unsubstituted derivatives, e.g., 260a-c, exist as a 1 1-3 1 mixture of the conformers 263 and 264. By contrast, N-substituted compounds, e.g. 261b and 262, favor the conformer 264. The conformer 263 is destabilized by an allylic interaction between R1 and R2, whereas the conformer 264 possesses an unfavorable 1,3-diaxial interaction between an oxide group and R1. Evidently, the latter interaction is less severe than the former when R1 and R2 are groups other than hydrogen atoms. 

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