Thiochromanes

The photochemical behavior of a number of substituted derivatives of thiochroman-4-one 1-oxides has been examined by Still and coworkers192-194. These authors also report that rearrangement to cyclic sulfenates, with subsequent reaction by homolysis of the S—O bond, appears to be a particularly favorable process. For example, ultraviolet irradiation of a solution of 8-methylthiochroman-4-one 1-oxide (133) in benzene for 24h afforded a single crystalline product which was assigned the disulfide structure 134 (equation 54). More recently, Kobayashi and Mutai195 have also suggested a sulfoxide-sulfenate rearrangement for the photochemical conversion of 2,5-diphenyl-l,4-dithiin 1-oxide (135) to the 1,3-dithiole derivatives 136 and 137 (equation 55). 

Scheme 6.71 Succinimide-containing substituted thiochromanes obtained from the 12-catalyzed enantio- and diastereoselective domino Michael-aldol reaction between 2-mercaptobenzaldehydes and maleimides.

In 2007, Wang and co-workers published a protocol for an enantio- and diastereoselective domino Michael-aldol reaction using electron-rich and electron-deficient 2-mercaptobenzaldehydes and maleimides as substrates [223]. The conversion was described to proceed smoothly in the presence of bifunctional catalyst 12 (lmol% loading) in xylenes at 0°C reaction temperature producing the desired chiral succinimide-containing substituted thiochromanes 1-5 in high yields (83-96%), in synthetically useful ee values (74—94%), and diastereoselectivities (up to dr 20 1) in 7h reaction time (Scheme 6.71). 

With established reaction parameters, this tandem process offered the facile synthesis of a range of substituted thiochromanes bearing three stereogenic centers. The reaction was reported to be high-yielding (75-97%) and produced the respective products 1-8 in excellent ee values (91-99%) as well as in very... 

Scheme 6.131 Typical thiochromanes obtained from the 121-catalyzed asymmetric thio-Michael-aldol tandem reaction between various 2-mercaptobenzaldehydes and a, 3-unsaturated oxazolidinones.

The 121-catalyzed synthesis of thiochromanes starting from 2-mercaptobenzal-dehydes and a,P-unsaturated oxazoHdinones was developed by the Wang group... 

Scheme 6.144 Thiochromanes prepared from the 121-catalyzed enantioselective tandem Michael-Knoevenagel reaction between 2-mercaptobenzaldehydes and diethyl methylenemalonates. The product configurations were not determined.

Thiochroman-4-ones result from the Pd-catalysed reaction of iodothiophenols with allenes and carbon monoxide <99JOC9646> and various thioflavonoids are accessible from acetoquinone via derived chalcones <99JOC359>. 

An intramolecular hetero-Diels-Alder reaction of o-thiobenzoquinone methides, generated in situ from bis(2-formyl-phenyl)disulfide and alkenols in the presence of iodine, has been used to prepare thiochromans (Scheme 22) <2003TL6513>. 

The focus will be directed to five ring systems thiochromans (1), thiochromones (2), isothiochromans (3), benzothiopyrans (4—6), and, benzothiopyrylium salts (7, 8). It is difficult completely to segregate their chemistry since they are so interrelated cross-references will be employed as often as possible. Thiocoumarins and thioxanthones are excluded since these molecules differ considerably from those reviewed here. 

Thiochroman-4-ones (1 R = 0) have been the most convenient synthetic entry into the thiochroman ring system. The most profitable of the various routes has been the acid-promoted cyclodehydration of (8-arylmercaptopropionic acids (9) [Eq. (1)]. The acids (9) result from... 

Thiochromans (1 R = H2) result from disproportionation of 2H- -benzothiopyrans (4) and also from thio-Claisen rearrangements of phenyl allyl sulfides. The first pathway was discovered by Tilak and Vaidya,24 who attempted to prepare one benzothiopyran (15) by cyclizing the /S-ketosulfide (14) in polyphosphoric acid (PPA), but obtained the thiochroman (16) and a benzothiopyrylium salt as in Eq. (5). This reaction involves25,26 an acid-promoted disproportionation... 

Thiochroman (1 R = Ha) is a product of the thio-Claisen rearrangement of allyl phenyl sulfide, as reported in 1963 27 this reaction also produces 2,3-dihydrothiophenes as shown in Eqs. (6) and (7).28,29... 

Similar reactions were carried out on 17,29 18,30 and 19.30 The last gave thiochromans and 2,3-dihydrothiophenes from an apparent cyclization at the ortho methyl substituent, but in fact involving a variety of hydrogen and methyl shifts. The route to the two main products [Eq. (7)] of the thio-Claisen rearrangement has been suggested to be via the thiirane intermediate (20).31... 

This rearrangement is also catalyzed by Lewis acids,32 but the products are more varied and this method is, therefore, less advantageous as a synthesis of thiochromans. 

Scheme 3 demonstrates similar reactions for thiochroman-4-one 1,1-dioxide (available from hydrogen peroxide oxidation of thiochroman 4-one).49... 

Chlorination11 of thiochroman-4-one is best achieved by cyclizing the requisite j8-arylmercaptopropionic acid (9) with phosphorus oxychloride. Conversions related to this are presented in Scheme 4. 

Thiochroman-4-ones are reduced to thiochroman-4-ols by sodium borohydride6 and lithium aluminum hydride.50 Lithium aluminum hydride reduction of thiofiavan-4-ones (27) forms the 2,4-ws-thiofiavan-4-ols (28) as in Eq. (8). By contrast, deamination of 2,4-cis-4-aminothio-flavans (29) with nitrous acid produced the trans- alcohol (30) as shown in Eq. (9).50 The alcohols obtained by the hydride reductions have... 

As mentioned (Section II, B), thiochroman-4-ones are readily reduced to the methylene level catalytically,33-35 under Clemmensen conditions,16,17 and, occasionally, with lithium aluminum hydride.63 The... 

Ring expansion of thiochroman-4-ones to 5-oxo-2,3,4,5-tetrahydro-1,4-benzothiazepines is accomplished by the Schmidt reaction, cf. Eq. (10).64... 

Hydrazones of thiochroman-4-ones are converted into thiochromans under Wolff-Kishner-Huang conditions65 and into the azo dimers by silver oxide.66 Fisher indolization of the phenylhydrazones (33) gives 6,ll-dihydrobenz[6]indolo[2,3-d]thiopyrans (34), which by hydride loss form the thiopyrylium salts (35), or on dehydrogenation produce the pseudoazulenes (36) (heterocyclic analogs of the carcinogen, benz[a]-carbazole), as shown in Scheme 6.87-73... 

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