Electrophiles thiophene complex

The synthesis and chemistry of metal complexes of thiophenes have been reported including the electrophilic additions to osmium-thiophene complexes <9902988> and nucleophilic additions to ruthenium-thiophene complexes <99JOMC242>. The selectivity for the insertion of ruthenium into 3-substituted thiophenes was studied <99CC1793>. For example, treatment of 3-acetylthiophene (84) with Ru(cod)(cot) led to a regioselective 1,2-insertion of ruthenium giving thiaruthenacycle 85. 

The reaction proceeds by formation of the electrophilic Vilsmeier complex 2.30, followed by electrophilic substitution of the heterocycle. The formyl group is generated in the hydrolytic workup. Pyrrole, thiophene, and furan all undergo this formylation which is highly selective for the C2 position. 

The 7] -osmium complexes of a-unsubstituted thiophenes undergo Lewis acid-promoted addition with acetals at C-2 to give the thiophenium complexes in good yields <19990M2988>. These can be deprotonated to give the 2-substituted thiophene complexes. The electrophile attacks the substrate on the rivn-face (Scheme 83). 

Thiophene complexes are synthesized by two-electron reduction of 77 -thiophene dicationic complexes. They are thus relatively electron rich and tend to react with electrophiles. 

The thiophene complex 10.161 can be prepared and displays some expected electrophilic reactivity (Scheme 10.41). ... 

An increasing volume in the literature is devoted to pseudo-cyclopentadienes and pseudo--arenes. A general paper describes complexation of the cyclo-Ps anion. The synthesis of the first diazacobaltocene has been described. Tert-butyl-substituted diazaferrocenes have been prepared from substituted pyrroles. Bis-(borole)nickel complexes have been prepared from dilithium txnelediides. Carborane stabilised iron indole and iron thiophene complexes have been made. The electrophilic stacking of borataferrocene and bis(borole)cobaltate ions with -Cr(CO)3 and Mn(00)3 has been described. The synthesis and crystal structure of... 

In view of the overall increased reactivity of furan compared with thiophene it would be anticipated that furan would be less regioselective in its reactions with electrophiles than thiophene. Possible reasons for the high regioselectivity of furan in electrophilic substitution reactions include complex formation between substrates and reagents and the ability of heteroatoms to assist in the stabilization of cationic intermediates (80CHE1195). 

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

Treatment of 2,7-di-/ert-butylthiepin (1) either directly with bromine at — 78 °C, or with pyridinium bromide perbromide at room temperature, gives the thiophene compound 2. In contrast, bromination with bromine-1,4-dioxane complex or pyridinium bromide perbromide in the presence of acetic acid leads to the thiopyran derivative 3.87 To account for these results a homothiopyrylium ion has been proposed as a common intermediate, formed by electrophilic bromination at C4 in the first step. 

Changes in intramolecular selectivity in the bromination and nitration of alkyl-benzenes in acidic media have been attributed to changes in medium polarity or changes in electrophile solvation. Mass spectrometric studies of the first stage in the gas-phase reactions of halobenzenes, furan, thiophene and pyrrole with alkyl cations have been rationalized in terms of co-existing a- and tt-complexes. The extent of... 

Semiempirical methods of calculation with consideration of all valence electrons have been used only recently but already have given results on the reactivities of some aromatic and heteroaromatic com-pounds. " Thus, to analyze the reactivities of thiophene and the isomeric thienothiophenes 1-3 to electrophilic substitution, the semiempirical SCF LCAO MO method CNDO/2 was used, taking into account all valence electrons.The 3s, 3p, and 3d orbitals have been taken into account for the sulfur atom. Tlie reactivities were estimated from the difference between bond energies of the initial and the protonated molecule (in a complex). ... 

In addition to benzene and naphthalene derivatives, heteroaromatic compounds such as ferrocene[232, furan, thiophene, seienophene[233,234], and cyclobutadiene iron carbonyl complex[235] react with alkenes to give vinyl heterocycles. The ease of the reaction of styrene with substituted benzenes to give stilbene derivatives 260 increases in the order benzene < naphthalene < ferrocene < furan. The effect of substituents in this reaction is similar to that in the electrophilic aromatic substitution reactions[236]. 

Vinyl ethers and amines disclose little tendency to revert to type thus, the intermediate formed by reaction with an electrophilic reagent reacts further by adding a nucleophilic species to yield an addition compound cf the sequence (8) — (11). Thiophene and pyrrole have a high degree of aromatic character consequently the initial product formed by reaction of thiophene or pyrrole with an electrophilic species subsequently loses a proton to give a substituted compound cf the reaction sequence (12) — (15). Furan has less aromatic character and often reacts by overall addition as well as by substitution. In electrophilic addition, the first step is the same as for substitution, i.e. the formation of a tr-complex (e.g. 13), but instead of losing a proton this now adds a nucleophile. 

The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared. Table 1 shows that the rates of substitution for (a) formylation by phosgene and V,iV-dimethylformamide, (b) acetylation by acetic anhydride and tin(IV) chloride, and (c) trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235) are all in the sequence furan > tellurophene > selenophene > thiophene. Pyrrole is still more reactive as shown by the rate for trifluoroacetylation, by the relative rates of bromination of the 2-methoxycarbonyl derivatives (pyrrole > furan > selenophene > thiophene), and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3]+ (Scheme 5) (2-methylindole ss V-methylindole > indole > pyrrole > furan > thiophene (73CC540)). 

The range of preparatively useful electrophilic substitution reactions is often limited by the acid sensitivity of the substrates. Whereas thiophene can be successfully sulfonated in 95% sulfuric acid at room temperature, such strongly acidic conditions cannot be used for the sulfonation of furan or pyrrole. Attempts to nitrate thiophene, furan or pyrrole under conditions used to nitrate benzene and its derivatives invariably result in failure. In the case of sulfonation and nitration milder reagents can be employed, i.e. the pyridine-sulfur trioxide complex and acetyl nitrate, respectively. Attempts to carry out the Friedel-Crafts alkylation of furan are often unsuccessful because the catalysts required cause polymerization. 

In the previous examples, the sulfur atom acted as a nucleophile. Electron-deficient sulfur species such as sulfenyl ion and its equivalents (e.g. disulfide/Lewis acid complexes, sulfenic acids, sulfenyl halides, sulfonium ions, sulfines, etc.), can also serve as an electrophile. Oxidative ring closure of enethiols (a-thioketocarboxylic acid) (124), which proceeds via disulfides, produces thiophenes (125) in good yields (86EUP158380, 88JHC367). 

Two excellent reviews <71AHC(13)235, 72IJS(C)(7)6l) have dealt with quantitative aspects of electrophilic substitution on thiophenes. Electrophilic substitution in the thiophene ring appears to proceed in most cases by a mechanism similar to that for the homocyclic benzene substrates. The first step involves the formation of a cr-complex, which is rate determining in most reactions in a few cases the decomposition of this intermediate may be rate determining. Evidence for the similarity of mechanism in the thiophene and benzene series stems from detailed kinetic studies. Thus in protodetritiation of thiophene derivatives in aqueous sulfuric and perchloric acids, a linear correlation between log k and —Ho has been established the slopes are very close to those reported for hydrogen exchanges in benzene derivatives. Likewise, the kinetic profile of the reaction of thiophene derivatives with bromine in acetic acid in the dark is the same as for bromination of benzene derivatives. The activation enthalpies and entropies for bromination of thiophene and mesitylene are very similar. 

The reactions of a,a -dibromoketones with iron carbonyls generate oxyallyliron complexes (75). These undergo cycloaddition with cyclopentadiene and furan, but with thiophene only products of electrophilic attack are obtained (78JA1765). Thus the oxyallyliron complex (75 R = Me R = H) reacts with thiophene to produce (76) in 37% yield. 

The reactivity of the five-membered heterocycles pyrrole, furan, thiophen and imidazole (Fig. 8-10) is characterised by interactions with electrophilic reagents. The precise nature of these reactions depends upon the particular ring system. Thiophens undergo facile electrophilic substitution, whereas the other compounds exhibit a range of polymerisation and other Lewis acid-initiated reactions upon treatment with electrophiles. We saw a number of examples of Lewis acid-promoted reactions of furans and pyrroles in Chapter 6. Although reactions of complexes of five-membered heterocyclic ligands have not been widely investigated, a few examples will illustrate the synthetic potential. 

Zirconium-benzyne complexes have been used rather extensively in organic synthesis.8 45 For this purpose, one particularly important characteristic of zirconium-aryne complexes is that olefin insertion into the Zr—C bond occurs stereospecifically. Thus, when generated in situ, the zirconium-benzyne complex (45) reacts with cyclic alkenes to give exclusively the cis-zirconaindanes (46), which upon treatment with electrophiles provide access to a variety of m-difunctionalized cycloalkanes (47-49) (Scheme 5).46 For example, carbonylation of intermediate 46 affords tricyclic ketone 49, reaction with sulfur dichloride gives thiophene 48, and reaction of 46 with tert-butylisocyanide followed by I2 gives 47 via 50 and, presumably, intermediate 51 [Eq. (12)]. 

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