2.4- Disubstituted benzo

After coupling of (hetero)aroyl chlorides 7 and terminal alkynes 4, ortho-ammo thiophenols 52 and acetic acid are added and reacted in the same reaction vessel under dielectric heating for 30 min at 60°C to furnish 2,4-disubstituted benzo[h][l, 5] thiazepines 53 via a coupling-addition-cyclocondensation sequence (Scheme 31) [193]. In the concluding heterocyclization step, dielectric heating is clearly superior over conductive heating. Although the Michael addition and cyclocondensation are essentially completed after 10 min at 60°C in the microwave cavity for electronically diverse substitution a reaction time of 30 min at 60°C has proven to be optimal. In contrast to 2,4-disubstituted benzo[h][l,4]diazepines 51 (vide supra), benzo[h] [1, 5]thiazepines 53 are essentially nonfluorescent. 

Disubstituted benzo[fc][l,5]thiazepines 53 can be obtained via three-component reaction consisting of modified Sonogashira cross-coupling I,... 

Disubstituted benzo[fo]furans were also prepared by intramolecular cyclisation in the presence of a [Pd(thiourea)4]l2 catalyst (thiourea = H2NCS NH2). No Pd precipitation occurred with this very stable thiourea complex (Scheme 31) [120]. 

At present, the chemisty of selenophenes and tellurophenes is a relatively scantily studied area. Nevertheless, a number of new valuable contributions dealing with their chemistry have emerged. Electrophilic cyclization of l-(l-alkynyl)-2-(methylseleno)arenes provides a route to a variety of 2,3-disubstituted benzo[fe]selenophenes, as illustrated by the preparation of the system 88. Other useful electrophiles for similar reactions are E or NBS <06JOC2307>. Similar chemistry has also been employed in preparation of 2,3-disubstituted benzo[f>]selenophenes on solid phase <06JCC163>. In addition, syntheses of 2,3-dihydroselenolo[2,3- >]pyridines have been achieved using radical chemistry <06OBC466>. 

The treatment of 2-fluorophenyl-2-iodophenyl ethers, amines, and thioethers with 3.3 equivalents of f-BuLi and further reaction with selected electrophiles gave rise to functionalized carbazoles, dibenzofurans, and dibenzothiophenes in a direct and regioselective manner. A selected example is illustrated below <06JOC6291>. Benzyl 2-halophenyl ethers was treated with f-BuLi, and then reacted with carboxylic esters to give 2,3-disubstituted benzo[t>]furans <06JOC4024>. 

As depicted in the following scheme, in the presence of sodium iodate and pyridine, several 5,6-dihydroxylated benzofuran derivatives were synthesized via an oxidation-Michael addition of P-dicarbonyl compounds to catechols in a one-pot procedure <06TL2615 06JHC1673>. A novel additive Pummerer reaction of 2-benzo[fc]furan sulfilimines with carbon nucleophiles derived from P-dicarbonyl compounds was also employed to the synthesis of 2,3-disubstituted benzo[b]furans <06TL595>. 

Conformational study by dynamic H NMR spectroscopy was also performed for some 1,3,2-dithiastannolanes differing by substituents at Sn and C atoms <82JCS(D)2073>. Vibrational, H NMR and MOssbauer spectra indicate that fused 2,2-disubstituted benzo-l,3,2-dithiastannolenes (1,3-dithia-2-stannaindanes) are associated in the solid (penta-coordination of tin) and monomeric in solution <85JOM(290)41>. 

For fused 2,2-disubstituted benzo- and quinazolino[2,3-c]-1,3,2-dithiaplumbolenes H NM R spectra including Pb- H spin-spin splittings are available <85JOM(290)4i>. 

A new approach to 2,3-disubstituted benzo[b]furans from o-alkynylphenols via 5-endo-dig-iodocyclization reaction was reported. The iodinated compounds are starting materials for a variety of substituted benzo[f>]furans <99SL1432>. 

Disubstituted Benzo[b]thiophenes 2,3-I)ibromobenzo[6]thiophene undergoes Friedel-Crafts acylation in the 6-position,77 but gives a mixture of the 4- and 6-nitro isomer on nitration.101 Similarly, 2,3-dimethylbenzo[b]thiophene undergoes Friedel-Crafts acetylation82,136,418 and bromination81 mainly in... 

Kumar, R.R. and Reddy, M.S., One-pot synthesis of 2,3-dihydro-2,3-disubstituted benzo[g]quinazolin-4(lH)-ones, Synth. Commuru, 1992, 22, 2499-2508. 

A flexible and convergent access to 2,3-disubstituted benzo[b]thiophenes has been developed (Scheme 22). The most concise approach involves a sequential coupling of an o-bromoiodobenzene with benzylthiol and zinc acetylides leading to the adduct 78. Treatment with iodine followed by an iodine/magnesium exchange and acylation provides the polyfunctional benzofuran derivatives. a... 

In the synthesis of symmetrically 3,8-disubstituted benzo[c]cinnolines 52 from the corresponding 4,4-disubstituted 2,2-dinitrobiphenyls 51, acetophenone has been used as reductant in a basic solution (Scheme 26) 2-nitroso-2-hydroxylaminobiphenyls are assumed to be intermediates in this reaction <2004JOC7720, CHEC-III(8.01.9.1)73>. 

Another type of 1,4-diazocine of stereochemical interest is that bearing an N,N -tetramethylene-o-phenylenendiamine moiety, exemplified by structures 86 and 89. A proton-NMR study showed that the heterocyclic ring of an N,N -disubstituted benzo-l,6-diazocine is in boat conformation 148, the boat boat interconversion barrier being more than 25 kcal/mol (76CJC1135). Saunders and Sprake used UV and H-NMR spectroscopy to study the N,lV -diacetyl-5,6,ll,12-tetrahydrodibenzo[h,/]-l,4-diazocine and concluded that there are four possible conformations (Scheme 5) with the interchange 150 151 (or 149 i=f 152) occurring more readily than 149 150... 

As shown in the following scheme, a SEM-ether derived phenyl acetylene was treated with PtClj in the presence of CO to give a benzo[4>]furan, which was first subjected to desilylation, followed by Pd-catalyzed intramolecular etherification, affording the tetracyclic skeleton of pterocarpane family of phytoalexins <05JA15024>. A similar type of synthetic transformation was so applied to make a key intermediate in the total synthesis of vibsanol <05JA15022>. 2,3-Disubstituted benzo[h]furans were prepared under very mild reaction conditions by the Pd/Cu-catalyzed cross-coupling of various o-iodoanisoles and terminal... 

A Pd-catalyzed tandem reaction was developed to synthesize a group of interesting benzo[fc] furans as depicted below <05CC271>. The Pd-catdyzed cyclization of propargylic carbonates was also applied to make 2,3-dihydrofurans and benzofurans <05T4381>. Furthermore, an oxidative cyclization procedure catalyzed by Pd(II) and pyridine in the presence of molecular oxygen was carried out on a variety of 2-allylphenols to form 2-substituted as well as 2,2-disubstituted benzo[fc]furans <05JA17778>. 

An efficient synthesis of roeaglaols was accomplished by development of a novel synthetic approach for the synthesis of its key intermediate by a-arylation of ketones 5EJOC1731>. The Pd-catalyzed Suzuki eoupling reaction was also applied to the syntheses of 23-disubstituted benzo[fo]furans <0 JO3334>. 

In connection with a total synthesis of frondosin B, the key intermediate shown below was synthesized by a sequential reaction of the phenol, the enyne and the bromide in a one-pot operation as shown <04OL457>. The palladium-catalyzed intramolecular C-0 bond formation between aryl halides and enolates was employed to make 2,3-disubstituted benzo[i> furans <04OL4755>. 

Active site directed thrombin inhibitors A broad screening approach for thrombin inhibitors led to the identification of the 2,3-disubstituted benzo thiophene derivative la (Fig. 5.9). A systematic structure-activity relationship study led to 31c which is 1271 times more potent. 

Likewise, several stable S,C-ylides derived from benzo[ >]thiophene and some 2,3-disubstituted benzo[i>]thiophenes have been reported recently <9iT86l l> by rhodium(II) acetate-catalyzed reaction with -icarbonyl diazo compounds. Ylides (e.g. (140)) from benzo[ >]thiophene and dibenzo-thiophene have also been reported by franj-ylidation using phenyliodonium bis(phenylsulfonyl)-methylide <88JHC1599>. 

An efficient approach to two types of 2,3-disubstituted benzo[fe]furans was reported by Rynn. In typical examples, the starting iodophenol was allowed to react with a phenylacetylene and an iodobenzene in the present of Pd(PPh,)jClj and MeMgCI with or without CO to lead to the 3-aroylbenzofuran (as shown) in the presence of CO, or to the 3-arylfuran in its absence <01CC1594>. 

Various 1,3-disubstituted benzo[c]pyran-5,8-diones are accessible by rearrangement of the transient Diels-Alder adducts from styrene and 2-substituted 1,4-benzoquinones <01T8653>. 

Copper(l) oxide nanoparticles catalyzed multicomponent coupling/ cycloisomerization reactions between various 2-hydroxybenzaldehydes, secondary amines, and nonactivated alkynes to give 2,3-disubstituted benzo [It] furans in good-to-excellent yields with high atom economy and high catalytic efficiency (14S2489). 

TAPA, I) resolves (by HPLC) polyaromatic hydrocarbons such as helicenes [14, 15], partially hydrogenated helicenes, 1,12-disubstituted benzo[c]-phenan-threne, napthophanes [16], naphthyl ethers [17], and diol epoxides of polyaromatic hydrocarbons. 

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