Thiophenes coupling with

Arylthiophenes. Thiophene couples with the diazohydroxides 3 and with N-nitrosoacetylamines 1 to give phenylthiophenes and derivatives. The position taken by the aryl groups in the thiophene nucleus has not been determined in all instances. The product obtained from diazotized wj-cyanoaniline and thiophene 3 in 19% yield appears to be the a derivative (XV).13... 

The cross-coupling of aromatic and heteroaromatic rings has been carried out extensively[555]. Tin compounds of heterocycles such as oxazo-lines[556,557], thiophene[558,559], furans[558], pyridines[558], and seleno-phenes [560] can be coupled with aryl halides. The syntheses of the phenylo.xazoline 691[552], dithiophenopyridine 692[56l] and 3-(2-pyridyl)qui-noline 693[562] are typical examples. 

Dyestuffs. The use of thiophene-based dyestuffs has been largely the result of the access of 2-amino-3-substituted thiophenes via new cycHzation chemistry techniques (61). Intermediates of type (8) are available from development of this work. Such intermediates act as the azo-component and, when coupled with pyrazolones, aminopyrazoles, phenols, 2,6-dihydropyridines, etc, have produced numerous monoazo disperse dyes. These dyes impart yeUow—green, red—green, or violet—green colorations to synthetic fibers, with exceUent fastness to light as weU as to wet- and dry-heat treatments (62-64). 

Radicaloid substitution has not been extensively studied in the thiophene series. Molecular orbital calculations indicate that substitution should occur in the a-position. This has been found to be the case in the Gomberg-Bachmann coupling of diazohydroxides with thiophenes which has been used for the preparation of 2-(o-nitro-phenyl) thiophene, 2-(p-toluyl) thiophene, " " and 2-(p-chloro-phenyl)thiophene. " Coupling in the /8-position has been used for the preparation of 1,3-dimethyl-4,5-benzisothionaphthene (148) from 2-amino-tt-(2,5-dimethyl-3-thienyl)cinnamic acid (149). A recent investigation describes the homolytic phenylation of 2- and 3-phenyl-... 

In —I—M-substituted aminothiophenes, the possibility of coupling during diazotization is eliminated. Thus ethyl 5-amino-2-thiophene-carboxylate and 5-amino-2-thiophenesulfonic acid and its amide- have been diazotized and coupled with various reagents. 

The synthetic utility of o-quinodimethane generated by cheletropic elimination of S02 has been amply demonstrated by Oppolzer and Nicolaou, who have conducted an intramolecular cycloaddition coupled with the alkylation of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide122. When 1,3-dihydro-l-(4-pentenyl)benzo[c]thiophene 2,2-dioxide (201) prepared from 1,3-dihydrobenzo[c]thiophene 2,2-dioxide and 4-pentenyl bromide is heated in di-n-butyl... 

The most widely accepted mechanism for the anodic polymerization of pyrroles and thiophenes involves the coupling of radical cations produced at the electrode (Scheme l).5 The oligomers so produced, which are more easily oxidized than the monomer, are rapidly oxidized and couple with each other and with monomer radical cations. Coupling occurs predominantly at the a-positions (i.e., 2- and 5-position),5 and so pyrroles and thiophenes with substituents in either of these positions do not undergo anodic polymerization. The reaction is stoichiometric in that two... 

An improved synthesis of dithieno[3,2-A2, 3 -<7]thiophene 15a has been achieved from 2,3-dibromothiophene 304 (Scheme 57). Lithiation of 2,3-dibromothiophene 304 using -butyllithium followed by oxidative coupling with cupric chloride provided 3,3 -dibromo-2,2 -bithiophene 305 in 79% yield. Treatment of 305 with 2 equiv of -butyllithium in ether at —78 °C under nitrogen for 40 min and then adding benzenesulfonic acid thioanhydride and leaving the reaction mixture to reach room temperature afforded dithieno[3,2-A2, 3 -<7]thiophene 15a in 70% yield <2002TL1553>. 

Treatment of thiophene r-butyl sulfonamide (59) with 2 equivalents of n-BuLi formed a dianion in which the second anion resided at the C(5) position. Quenching the resulting dianion with triisopropylborate followed by acidic workup furnished thienylboronic acid 60, which was then coupled with p-bromobenzyl alcohol under basic conditions to afford arylthiophene 61 [49]. 

Liebeskind and associates converted 3,4-diisopropyl squarate (97) to stannylcyclobutenedione 98 via a 1,4-addition-elimination sequence. 98 was then coupled with 2-iodothiophene to afford substituted cyclobutenedione 99 [85]. In another case, 3-lithioquinuclidin-2-ene, generated from the Shapiro reaction of 3-quinuclidinone (100), was quenched with Bu3SnCl to afford a unique enamine stannane 101. The Stille reaction of stannane 101 and 5-bromo-2-formyl-thiophene then furnished 3-thienylquinuclidine 102 [86]. 

A tremendous amount of work has been reported on the synthesis of arylthiophenes and heteroarylthiophenes utilizing the Stille reaction approach. In one case, 2-tributylstannylthiophene was coupled with p-acetoxyphenyl iodide to give thienylphenol 114 after hydrolysis [93]. In another, the union of 2-tributylstannylbenzo[fc]thiophene and p-acetyliodobenzene provided arylbenzothiophene 115 using inexpensive Pd/C as a heterogeneous catalyst, Cul as a co-catalyst, and AsPh3 as a soft ligand [94], Moreover, Kennedy et al. coupled 2-tributylstannylthiophene and 2-chloro-4-bromobenzylphosphonate (116) to make heterobiaryl... 

Sonogashira reactions of both a-halothiophenes [117] and P-halothiophenes [118] proceed smoothly even for fairly complicated molecules as illustrated by the transformation of brotizolam (134) to alkyne 135 [119]. Interestingly, 3,4-bis(trimethylsilyl)thiophene (137), derived from the intermolecular cyclization of 4-phenylthiazole (136) and bis(trimethylsilyl)acetylene, underwent consecutive iodination and Sonogashira reaction to make 3,4-bisalkynylthiophenes [120], Therefore, a regiospecific mono-i/wo-iodination of 137 gave iodothiophene 138, which was coupled with phenylacetylene to afford alkynylthiophene 139. A second iodination and a Sonogashira reaction then provided the unsymmetrically substituted 3,4-bisalkynylthiophene 140. 

Stannylthiazoles have also been coupled with an array of heterocyclic halides. Reaction of 2.4 equivalents of 2-trimethylstannylthiazole with 2,5-dibromothiophene gave 2,5-di-(2 -thiazolyl)-thiophene (62) [40]. Similarly, Dondoni s group coupled 2,5-dibromothiazole with 2 equivalents of 2-trimethylstannylthiazole to assemble trithiazole 63 [41],... 

Along with some disubstituted furan 59, mono-arylation product 58 was isolated when 2-chloro-3,6-diethylpyrazine (57) and furan were refluxed in the presence of Pd(Ph3P)4 and KOAc. In the case of 2-chloro-3,6-dimethylpyrazine (23) and thiophene, monothienylpyrazine 60 was the sole product. When 2-chloro-3,6-diisobutylpyrazine was used as substrate, 9% of the disubstituted thiophene was detected. Analogous to the couplings with furan and thiophene, the heteroaryl... 

Halopyrimidines also couple with stannanes of heterocycles such as furans [41], azaindoles [42], pyridines [43-46], thiazoles, pyrroles [46] and thiophenes [47], A representative example is the coupling of 3-tributylstannyl-7-azaindole 72 with 5-bromopyrimidine to furnish heterobiaryl 73 after acidic hydrolysis [42]. Moreover, a selective substitution at the 5-position was achieved when 4-chloro-5-iodopyrimidine 74 was allowed to react with 2-thienylstannane to provide thienylpyrimidine 75 [47]. 

Falck has recently reported dehydrogenative silylation of heteroarenes with triethylsilane (18) [97]. Coupling with the Si-H bond of triethylsilane, rather than the disilane Si-Si bond, in conjunction with the use of norbomene that presumably acts as a hydrogen acceptor, gives good yields with indoles, thiophenes, and furans, under relatively mild condition (80°C). Unlike the reaction shown in Scheme 7, silylation of indole did not require protection of the N-H group. 

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