Lithium derivatives of thiophene

Reactions of lithium derivatives of thiophene with octafluorocyclopentene... 

The most widely used method for the preparation of perfluorocyclopen-tene-containing DTEs is based on the reactions of lithium derivatives of thiophene with octafluorocyclopentene (98KGS927, 99IZV979, 99JP183). This method is used for the assembly of photochromic products from components indifferent to butyllithium or for the formation of the core of the molecules for their subsequent functionalization. This approach is suitable for the synthesis of both symmetrical and unsymmetrical photochromes. 

Reactions of Lithium Derivatives of Thiophene with Octafluorocyclopentene.. 521... 

The main method for the preparation of perfluorocyclopentene DHE used in the majority of studies is the reaction of the lithium derivatives of thiophene with octafluorocyclopentene [43 5, 41]. The photochromic products are thus assembled from the components indifferent to butyllithium or the molecule backbone is formed for further functionalization. This approach allows one to synthesize both symmetrical and unsymmetrical photochromes. 

The reaction of the lithium derivatives of thiophene with 1 can be accompanied by the formation of the products of substitution of only one fluorine atom at the double bond of cyclene. For example, photochrome 37 was synthesized (Scheme 10) either in one stage with a twofold excess of the lithium derivative 35 over perfluorocyclopentene or in two stages with the preliminary isolation of monofluoride 36 [46]. 

Not only lithium derivatives of thiophene and also of other heterocycles, particularly, thiazole (Scheme 30), react with perfluorocyclopentene to form photochromes. As a rule, the yields of the thiazole derivatives are significantly inferior to those for the thienyl derivatives [79-82]. 

A limited number of non-transition-metal derivatives of thiophene will be considered in this subsection. There are no short-range contacts between the lithium atoms originating from the (LiO)6 cores and the sulfur atoms in [Li—O—EMc2 (2-C4H3S)]6 (E = C, Si) (97OM5032), and evidence for Tr-interactions can be found in the X-ray crystal structures of these compounds. Theoretical computations show that a- (S ) Li" " interactions are weak, whereas Tr-Li" contributions are considerable, in accord with the general reasoning on the electronic characteristics of uncomplexed thiophene. 

The reaction of heterocyclic lithium derivatives with organic halides to form a C-C bond has been discussed in Section 3.3.3.8.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp2 carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable heterocyclic metal derivative. The metal is usually zinc, magnesium, boron or tin occasionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated heterocycles with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. 

Halogen-metal exchange can also be conveniently used to prepare lithium derivatives of benzo[7 ]thiophene. Some examples are shown in Scheme 168 <70AHC(ll)l77. ... 

Carbonation of the lithium derivative of 2-methoxybenzo[6]thio-phene affords the corresponding 3-carboxylic acid.183 2-Methylbenzo-[6]thiophene-3-carboxylic acid has been obtained (45%) by carbonation of 2-benzo[6]thienylmethylmagnesium chloride (Section VI,D, 4).528 re-Butyllithium reacts selectively with the bromine atom in 3-bromo-2-fluorobenzo[b]thiophene to give a product, which on carbonation affords 2-fluorobenzo[6]thiophene-3-carboxylic acid.482 Benzo[6]thiophene-7-carboxylic acid is obtained by reduction of the corresponding thioindoxyl with amalgamated zinc and acetic acid.315 Benzo[6]thiophene-3-carboxylic acid and its 2-ethyl derivative have been prepared in high yield by treatment of the pyridinium salt of the 3-chloroacetyl derivative with alkali.132... 

The one-bond CC coupling data for the lithium and 2-methyl derivatives of thiophene are collected in Table 42. The 7cc couplings for a series of substituted thiophenes are presented in Table 43. The 7ch ( = 1-3) couplings are given in Tables 44 and 45. In Table 44, the couplings = 3-5) are collected in Table 45, the Jch and in... 

Bromine derivatives of thiophene are the most widely used for the preparation of isomeric thienothiophenes and related systems. A classical example is illustrated by the following transformation sequence formylation of 3,4-dibromothiophene (1) through lithium derivatives, repeated metallation and treatment with elemental sulfur and methyl bromoacetate. Ring closure of the second heterocycle occurs in the present of sodium alkoxide. Decarboxylation of the resulting 4-bromothieno[2,3-Z ]thiophene-2-carboxylic acid (2a) affords 3-bromothieno[2,3-Z)]thiophene (3a) (74IZV1570). The reaction with selenium instead of sulfur produced 4-bromosele-nolo[2,3-Z ]thiophene-2-carboxylic acid (2b) and 4-bromoselenolo[2,3-Z)]thiophene (3b). 

Lithium derivatives of thieno[3,2-fe]thiophene (145) were used in the synthesis of 2-arylthieno[3,2- )]thiophenes 152 through various organometallic (or -boron)... 

Thienyl-lithium derivatives prepared through halogen-metal exchange and containing acetal-protected carbonyl groups have been used in the synthesis of di- and tri-formyl derivatives of thiophen, t-butoxy-sub-stituted thiophen aldehydes, and formylacetylthiophens. Symmetrical thienyl-substituted ketones have been obtained from thienyl-lithium derivatives and carbamates. " Mixed heterocyclic carbinols have been obtained through the reaction of thienyl-lithium derivatives with heterocyclic aldehydes. Thienyl-lithium derivatives react with cyclohexanone, and various phenylthiophens have been made by aromatization of the intermediate cyclohexenyl derivative. The reaction of thienyl-lithium derivatives with NN-dimethylacetamide, which has been used for the synthesis of... 

Carbon-sulfur bonds can be formed by the reaction of elemental sulfur with a lithio derivative, as illustrated by the preparation of thiophene-2-thiol (201) (700S(50)104). If dialkyl or diaryl disulfides are used as reagents to introduce sulfur, then alkyl or aryl sulfides are formed sulfinic acids are available by reaction of lithium derivatives with sulfur dioxide. 

Catalytic reduction of thiophenes over cobalt catalysts leads to thiolane derivatives, or hydrocarbons. " Noncatalytic reductions of thiophenes by sodium or lithium in liquid ammonia leads, via the isomeric dihydrothiophenes, to complete destructions of the ring system, ultimately giving butenethiols and olefins. " Exhaustive chlorination of thiophene in the presence of iodine yields 2,2,3,4,5,5,-hexachloro-3-thiolene, Pyrolysis of thiophene at 850°C gives a... 

The bromination behavior of isomeric thienothiophenes (53-55) has been studied in detail. Both the [2,3-b] (53) and the [3,2-h](54) isomers reacted with one equivalent of NBS in acetic acid to give an a-monobrominated product, with some evidence of 2,5-dibromo species also being formed. With 2 mol of NBS these latter products were formed in good yield three molar equivalents led to 2,3,5-tribromothieno-[2,3-h]-and -[3,2-6]-thiophenes (Scheme 28). The monobromo compounds can also be prepared from lithium derivatives quenched with bromine [76AHC( 19) 123]. Apparently the [2,3-c]isomer (55) also reacted initially in the 2-position. 

Shatenshtein et al.5 5 5- 591 have also measured rate coefficients for dedeuteration of thiophen derivatives by lithium or potassium l-butoxides in dimethyl sulphoxide or l-butyl alcohol (70 vol. %) in diglyme (Table 178). Interestingly, the 2 position is more reactive than the 3 position and this was reasonably attributed to the —I effect of the hetero sulphur atom. The methyl substituent lowers the reactivity of the 2 position from each position in accord with its +1 effect and consequently the effect was greatest from the 3 position. However, the deactivation from the 5 position was greater than from the 4 position, and this was incorrectly attributed to the +M effect of methyl group operating from the 5 position since... 

Water-soluble derivatives of polythiophene have been made allowing counterions bound to the polymer backbone to self-dope with the protons (e.g., lithium and sodium ions) injecting electrons into the pi-system. Thus, combinations of sodium salts and proton salts (e.g., prepared from poly-3-(2-ethanesulfonate)thiophene) have been prepared that are both water-soluble and conducting. 

All the above examples refer to thiophenes containing functional groups indifferent to the presence of butyllithium. In reactions with reagents in an equimolar ratio, it is highly probable that only one of the fluorine atoms at the double bond of cyclene will be replaced. For example, the target product 26 (Scheme 8) was prepared by either a one-pot reaction in the presence of a twofold excess of lithium derivative 24 with respect to per-fluorocyclopentene or in two steps including the isolation of monofluoride 25 (99IZV10n). 

Another method for e preparation of aryl w-dimethoxyethyl sulfides was described by Pandya and Tilak. The procedure consists in allowing aryl lithium derivatives to react with 2,2,2, 2 -tetramethoxy-diethyl disulfide. Subsequent cyclization of the sulfides by polyphos-phoric acid yields 2-35% of condensed thiophenes and thiopyrans. By this method, thienothiophene 1 was prepared from 2-thienyllithium [Eq. (12)] and the previously unknown dithieno[2,3-6 3, 2 -i/]thiophene (5) was obtained from thienyl-2,5-dilithium. The possibility of synthesizing a heterocyclic analog (25) of pentacene from dithieno[2,3-6 3 2 -[Pg.130]

Bugge brominated thienothiophenes 1 and 2 with IV-bromo-succinimide in glacial acetic acid to 2-bromothieno[2,3-6]thiophene (66%) and 2-bromothieno[3,2-6]thiophene (55%). The structure of 2-bromothieno[2,3-6]thiophene was confirmed by the replacement of bromine by lithium at —70° followed by carbonation to thieno[2,3-6j-thiophene-2-carboxylic acid 2-bromothieno[3,2-fe]thiophene was independently prepared by the treatment of 2-lithiothieno[3,2-6]thiophene with one equivient of bromine at —70°. The 2-bromo derivatives of thienothiophenes 1 and 2 decompose within several hours at 20°, but remain uncWged for weeks at —15°. 

Butyllithium effects C-2 lithiation, and the lithium derivative can then be reacted with electrophiles (this is a good way to synthesize a wide variety of 2-substituted thiophenes) (Scheme 6.36). 

A number of cycloalkyl-, vinyl-, aryl-, and benzyllithium compounds (predominantly benzyl-lithiums) are converted into fluoro derivatives in good to excellent yields, e.g. formation of 4, 5, and 6 19 however, when this method was applied to the synthesisof 3-fluorobenzocyclobutene from the lithium salt a violent explosion occurred when the reaction mixture was warmed from — 70 C to room temperature.20 Various fluoro-substituted thiophenes 7 are obtained when the starting compounds (thiophene, 2-methylthiophene, etc.) arc transformed with al-kyllithium compounds to the corresponding lithium derivatives then fluorinated with perchloryl fluoride at 0 C.21 Potassium tricyanomethanidc is converted at —15 C in triglyme into tricyanofluoromethane in 81 % yield.22... 

Pyrroles are not reduced by sodium in liquid ammonia, but the Birch reduction of 2-furoic acid with lithium in liquid ammonia gives the 2,5-dihydro derivative in 90% yield (780PP94). Sodium-liquid ammonia-methanol reduction of thiophene gives a mixture of A2- and A3- dihydrothiophenes together with butenethiols. Reductive metallation of 1,3-diphenylisobenzofuran results in stereoselective formation of the cis- 1,3-dihydro derivative (Scheme 36) (80JOC3982). 

---