Dihydrothiazine imine

Bis-imines (117) have been used far less than the monoimines as dienophiles. However, there are enough examples of these cycloadditions to indicate clearly that they are regioselective and, provided at least one electron-withdrawing group is present on nitrogen, that they proceed under mild reaction conditions. As with the monoimines, little is known with regard to the establishment of sulfur stereochemistry in the dihydrothiazine imines (118). Equations (55)," (56) and (57) demonstrate both the regio-selectivity of the process and some of the structural types of bis-imino compounds which have been... 

Weinreb and coworkers have examined some reactions of dihydrothiazine imines and have developed a new approach to vicinal diamines using these intermediates. Their method is outlined in Scheme 18. Cycloaddition of ( -2,4-hexadiene with the tosyl bis-imine gives a 1.1 1 mixture of epimeric dihydrothiazine imines (140) and (144). Subsequent transformations of these adducts took two different courses. In one, adduct (140) could be opened to allylic sulfilimine (141) which underwent a stereoselective 2,3-sigmatiopic rearrangement to sulfenamide (142) (cf. equation 54). Desulfurization of (142) yielded E)-threo vicinal sulfonamide (143). Adduct (144), which presumably exists in conformation... 

In a similar fashion, 3,6-dihydrothiazine 1-imines can be cleaved by several alkyl and aryl organometallic reagents. Dihydrothiazine imines have more steric and electronic constraints compared to the corresponding oxides, and hence some are very resilient to ring opening by nucleophiles. Treatment of imine (80a) with phenylmagnesium bromide at — 60°C gave a product which was... 

Even though the sulfilimine (83) undergoes a [2,3]-sigmatropic rearrangement, unlike the sulfoxide/sulfenate rearrangement the equilibrium here lies toward the sulfenamide (84) (Scheme 14). This difference in reactivity plays a very critical role in the stereochemical outcome in the conversion of some dihydrothiazine imines to vicinal diamines. 

The adducts formed in these cases are the analogous dihydrothiazine imines 2. Symmetrical and unsymmetrical sulfur diimides are available, and both can act as heterodienophiles. In adducts 1 and 2 the sulfur center is chiral, and the implications of this fact will be discussed in some of the following sections. 

X-Ray crystallography has also established that dihydrothiazine imines have similar conformations. For example, compounds 36 and 38 were found to have half-chair conformations (cf. Scheme 1-IV), once again with the sulfur-heteroatom bond quasi-axial. Adduct 37 was correlated with 36 by lanthanide-induced shift H-NMR experiments, and the data have been interpreted as supporting this same type of conformation. ... 

There are several well-known transformations of 3,6-dihydrothiazine oxides and 3,6-dihydrothiazine imines. In most of these reactions, either the cyclic sulfinamide moiety and/or the carbon-carbon double bond is involved. For example, a 3,6-dihydrothiazine oxide can be hydrolyzed under either acidic or basic conditions to afford a homoallylic amine derivative [Eq. (17)]. 

The cycloadducts of sulfur diimides exhibit hydrolytic behavior very similar to that of dihydrothiazine oxides (Scheme 1-XI). Alkaline hydrolysis of a dihydrothiazine imine affords an intermediate sulfinamide which, on treatment with aqueous acid, yields a homoallylic amine, presumably via a retro-ene process. A homoallylic amine is formed directly from a cycloadduct on acidic hydrolysis. ... 

This transformation presumably proceeds with initial formation of allylic sulfilimine 55, which rearranges via an envelope-like transition state to sulfenamide 56 (cf. Scheme 1-XIU). Interestingly, NMR analysis showed that this [2,3]-sigmatropic rearrangement lies totally on the side of this sulfenamide, unlike the allylic suUbxide-sulfenate ester system, which lies predominantly to the side of the sulfoxide. Similarly, C-3 epimeric dihydrothiazine imine 58 can be converted by an identical pathway to E-erythrp vicinal diamine 59 in an efficient and totally stereoselective manner [Eq. (28)]. 

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... 

The Weinreb group has recently developed stereoselective methodology for synthesis of unsaturated vicinal diamine derivatives from dihydrothiazine imines.49 For example, when cycloadduct 54 prepared from (E, )-2,4-hexadiene was treated with phenylmagnesium bromide followed by trimethyl phosphite, E-threo vicinal diamine 57 was formed cleanly in good yield [Ea. <27)1. 

Two general classes of V-sulfinyl compounds have been employed as dienophiles. The most widely utilized type are N-sulfinyl species (115), formally monoimines of sulfur dioxide, which produce 3,6-di-hydrothiazine 1-oxides (116) (Scheme 14) upon cycloaddition. - -phe analogous bis-imines of sulfur dioxide (117) have also been used upon occasion as dienophiles to yield the 3,6-dihydrothiazine 1-imines (118). Both processes show excellent regioselectivity and are syn stereoselective with respect to the... 

Since 3,6-dihydrothiazine 1-imines exist in conformations having a quasi-axial S—N bond, these imines are properly disposed stereoelectronically for such a pericyclic process. This reaction is essentially irreversible, similar to the equilibrium in a [2,3]-sigmatropic rearrangement of allylic sulfilimines (55), which lies to the side of the sulfenamide (56) (Scheme 11). There is a clean transfer of stereochemistry from C-6 of the dihydrothiazine (52) to C-4 of the thiadiazolidine (53), leading to the (E)-erythro-vicinal diamine derivative (54). In a similar fashion, thermolysis of the epimeric imine (57) gives the thiadiazolidine (58), which can be converted into the Z)-threo-vicinal diamine... 

In the absence of any substituent at the C-6 position, the sulfur stereochemistry controls the stereochemical outcome of the [2,3]-sigmatropic reaction, and hence the imine (60) can be stereo specifically converted to the cw-thiadiazolidine (61) <88JOCl 116>. The epimeric dihydrothiazine... 

The 3,6-dihydrothiazine 1-oxides and 1-imines are susceptible to ring cleavage with a variety of nucleophiles. Wucherpfennig investigated the S—N bond cleavage of 3,6-dihydrothiazine 1-oxides... 

The second aspect which is different in the case of the 3,6-dihydrothiazine 1-imines (80a) and (82a) as compared to the 1-oxide (73) involves the reactivity of the resulting allylic sulfilimine... 

These A-sulfinyl Diels-Alder reactions are also highly stereoselective, giving products of syn addition to the 1,3-diene. The same holds true for the sulfur diimide cycloadditions . The stereoselectivity with respect to the dienophile is not very well known because the stereochemistry of sulfur in the starting A-sulfinyl dienophile and in the resulting thiazine derivatives has usually not been determined. A representative sample of the stereoselective preparation of 3,6-dihydrothiazine 1-oxides and 1-imines is shown in Scheme 34 <84JA786i, 84JA7867>. 

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