Thiochromenes

The colored form of 2,2-diphenyl-2//-thiochromene (thio analogue of chromene) absorbs at 650 nm in 3-methylpentane at 77 K.71... 

ThrePHOX 6b proved to be a valuable tool in the reduction of chromenes 71a-k, all of which were reduced in greater than 90% enantioselectivity. The very electron-rich thiochromene 71h required higher temperature, and lower conversion was observed, but the enantioselectivity remained in the useful range (Table 13) [96]. 

Application of an organocatalytic domino Michael addition/intramolecular aldol condensation to the preparation of a series of important heterocycles has recently received much attention [158] with methods being disclosed for the preparation of benzopyrans [159-161], thiochromenes [162-164] and dihydroquinolidines [165, 166]. The reports all use similar conditions and the independent discovery of each of these reactions shows the robust nature of the central concept. A generalised catalytic cycle which defines the principles of these reports is outlined in Fig. 10. Formation of iminium ion 102 is followed by an intermolecular Michael addition of an oxygen, sulfur or nitrogen based nucleophile (103) to give an intermediate... 

Thiochromenes (e.g., 15) are converted to thiocoumarins by oxidation with chromium trioxide in pyridine. In a similar way thiochromylium salts (e.g., 16) are converted to thiocoumarins by oxidation with either active... 

Attempts to cyclize the keto sulfide (282) with polyphosphoric acid at temperatures greater than 100 °C gave as the major product the 2-isopropyl-3-methylthiophene (284). When the cyclization was conducted at lower temperatures, the thiochromene (283) was the major product. Since 4-phenylthio-2-butanone cyclized to produce a stable thiochromene, the quaternary carbon in (283) which can form a stable carbenium ion (284a)... 

Figure 5 shows the molecular structures of rfs-2-nitro-7-(dimethylamino-)-9-(2,3,-dihydro-l J-f-naphtho[2,l-b]thiopyran-l -ylidene)-9J-f-thioxanthene ((P)-cis-17) and trans-dimethyl-[l-(2-nitro-thioxanthen-9-ylidene)-2,3-dihydro-lJ-f-ben-zo[f]thiochromen-8-yl]amine ((P)-trans-18). Anti-folded helical structures, in which the top and bottom parts are respectively tilted up and down relative to the plane of the central olefmic bond, are clearly observed. The extent of folding and twisting in these and related overcrowded alkenes can vary considerably. It should be emphasized that only minor deviation from planarity occurs at the central double bond (dihedral angles 5.4° (17) and 6.8° (18)), while normal bond lengths are found (1.353 A (17) and 1.338 A (18)).130,311... 

The benzologues of the thiopyrans are 2/7-1-benzothiopyran 10, which is also referred to as 2//-thiochromene, and 4//-l-benzothiopyran 11 (4//-thiochromene). Fusion on to the 3,4-bond of 2//-thiopyran leads to 1 //-2-benzothio-pyran 12 and 3//-2-benzothiopyran 13. Higher benzologues are named as 9//-thioxanthene 14, l//-thioxanthene 15,... 

Acetalization of thiochroman-3-one gives a 1 1 diastereomeric mixture and subsequent oxidation with Davis reagent, W-(phenylsulfonyl)(3,3-dichlorocamphoryl)oxaziridine, yielded the sulfoxides each with a 4 1 enantioselectivity. Chiral chromatographic separation of the diastereomers preceded isolation of the major enantiomers. (3-Elimination and isomerization of the double bond then produced the individual thiochromene 1-oxide diastereomers. The generation of an a-sulfinyl carbanion effects the cleavage of one of the acetal C-O bonds with the protected diol released in a final ozonolysis step. The stereochemical results indicate that it is the C-O bond syn to the sulfoxide function that is cleaved (Scheme 63) <1996TA29>. 

Thiochromen 4-yl enol phosphates have been obtained from 2 -fluoroacetophenone through initial reaction with prop-2-enethiol followed by conversion to the enol phosphate. Ring closing metathesis (RCM) using a second generation Grubbs catalyst delivered the. V-hctcrocycle. Oxidation at sulfur prior to RCM provided access to the thiochromen-4-yl 1,1-dioxide enol phosphate (Scheme 120) <2003TL4275>. 

Dithiodibenzaldehyde behaves as a masked thiosalicylaldehyde and undergoes a Baylis-Hillman reaction with electron-deficient alkenes to give 3-substituted thiochromenes (Scheme 124) <2001S2389>. 

Reaction of the naphthalene-based a,(3-unsaturated thioketone 478 with various acrylate dienophiles leads to the benzo-fused thiochromans 479 from which elimination of the phenylthio group, which may require the addition of base, affords the benzo-fused thiochromenes (Scheme 168) <1992BCJ2056>. These latter products are themselves suitable substrates for hDA reactions which produce dithiabenzo[c]chrysenes 480 <1994BCJ2876>. 

Thiosalicylaldehydes afford chiral thiochromene-3-carbaldehydes 39 on reaction with a,P-unsaturated aldehydes catalysed by a chiral pyrrolidine silyl ether. Initial activation of the enal triggers sequential Michael and aldol reactions and dehydration completes the highly enantioselective synthesis <06JA10354, 06TL8547>. In a similar manner, cyclic enones afford cycloalkanone[ ]thiochromenes <06TL8679>. 

The carbonyl group is easily converted to the thiocarbonyl, yielding 1,2-dithiocoumarin, by the action of phosphorus pentasulfide. - The chemistry of the dithiocoumarins is discussed separately (see p. 131). Interaction of thiocoumarin with phenylmagnesium bromide gives low yields of thioflavone (19) and the thiochromene 20, probably by way of the thiobenzo-pyrylium salt (18, Scheme 1... 

Linder acid-catalyzed conditions, this same benzoyl derivative rearranges, presumably via a ring-opened intermediate, to a thiochromene (Eq. 1) Thiochromenes are also derived from the action of a Grignard reagent on a dihydrothiocoumarin (Scheme 23). 

In general, 4//-thiochromen-4-ones are synthesized either by condensation of p-keto esters and thiophenols with pol3q)hosphoric acid [213-215] or by cyclization of p-substituted cinnamates derived from thiophenols and appropriate propiolates [211, 216, 217]. 

Scheme 45 Coupling-addition-nucleophilic aromatic substitution three-component synthesis of 4//-thiochromen-4-ones 82, 4/f-thiopyrano[2,3-i)]pyridin-4-ones 83, 2-chloro-4/f-thieno[2,3-b] thiopyran-4-ones 84, or 7//-benzo-[b]thieno[3,2-i)]thiopyran-7-ones 85...

Scheme 46 Mechanistic rationalization of the coupling-addition-nucleophilic aromatic substitution sequence to annelated 4//-thiochromen-4-ones 82-85...

Willy B, Muller TJJ (2009) A novel consecutive three-component coupling-addition-S /Ar (CASNAR) synthesis of 4H-thiochromen-4-ones. Synlett 1255-1260... 

It is remarkable that both reactants, the 4-silyloxy-l-benzothiopyrylium-salts 1 as well as the 2-silyloxy-1,3-butadienes 2, are formed in situ in one pot. First, the 4-silyloxy-l-benzothiopyrylium-salt 1 is obtained from the thiochromen-4-one 6 by treatment with a trialkylsilyltriflate [8] and then, the 2-silyloxy-1,3-butadiene 2 is formed by treatment of methyl vinyl ketone 7 with a trialkylsilyltriflate and 2,6-lutidine in the same flask. 

The thiochromene 31 is the final product arising from the photoirradiation of tris-(2-benzo-[i]thienyl)methane. The primary photoproduct is a cyclopropane derivative formed by a di-3t-methane rearrangement <03TL751>. 

In some systems, however, thiochromenes (e.g. 32) are formed " , and it is suggested that initial attack may occur on an aromatic carbon rather than on an alkyne carbon of the diphenylacetylene. 

V I. Minkin, B. Y. Simkin, L. E. Nivorozhkin, and B. S. Luk yanov, Photo- and thermochromic spirans. IV. Theoretical study of electron structure and spectra ofvalence isomers of 27/-chromenes, thiochromenes and 1,2-dihydroquinolines, Khim. Geterotsikl. Soedin. 1974, 67-75 Russ. Chem, Rev. 59, 685-692 (1990)]. 

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