Electron-rich thiophenes

The electron-rich thiophene ring system can be elaborated into complex, fused thiophenes by acid-mediated intramolecular annelation reactions. For example, treatment of alcohol 96 with trimethylsilyl triflate promoted a Friedel-Crafts acylation and subsequent dehydration giving benzo[b]thiophene 97, a potential analgesic <00JMC765>. Treatment of ketone 98 with p-toluenesulfonic acid resulted in the formation of fused benzo[b]thiophene 99 <00T8153>. Another variant involved the cyclization of epoxide 100 to fused benzo[f>]thiophene 101 mediated by boron trifluoride-etherate . 

Although excellent yields of the unsaturated amides and urethans could be obtained, hydrolysis of the urethans gave poor yields of the aldehyde. The application of the Curtius degradation resulted in excellent yields of the various intermediates and a fair yield of the aldehyde. It appears that the presence of the heterocyclic moiety renders these aldehydes less stable than the corresponding aldehydes in the benzene series. Possibly the electron rich thiophene ring bestows a higher reactivity on the hydrogen atoms of the methylene carbon. 

The electron-rich thiophene ring system can be annelated by intramolecular Friedel-Crafts acylation reactions to give fused thiophenes <99IJC648, 99JMC2774>. The synthesis of a thiophene isostere of ninhydrin involved an intramolecular Friedel-Crafts acylation <99SL1450>. Specifically, treatment of thiophene 86 with thionyl chloride followed by aluminum chloride gave annelated thiophene 87. The synthesis of isothianinhydrin 88 was then accomplished in six steps from 87. 

A combination of electron-rich thiophene units with relatively electron-deficient fluorene units should modify the bandgap of the material (and thus tune the emission) and improve the charge injection/transport balance compared to fluorene homopolymers. 

Narrowing the bandgap of copolymers by alternation of electron-rich thiophene and electron-deficient benzo-l,2,3-thiadiazole units was used in the design of several LEPs whose optical and electronic properties could be tuned through such a modification. Cao and coworkers synthesized copolymers 599 and 600 (02MI2887 04MM6299), exploiting random copolymerization. 

N-Alkylation and subsequent reduction of both thieno[3,2-c]- (422) and thieno[2,3-c]pyridines (424) give predictably the 4,5,6,7-tetrahydrothieno-pyridines 423 and 425, respectively. Large excesses of borohydride were used, and the reductions were carried out in ethanol over 4-h periods at reflux temperatures. Yields of 57-78% are obtained. The relatively electron-rich thiophene ring resists reduction. 

The electron-rich thiophene and benzothiophenes are widely used as isosteres of their phenyl cousins in medicinal chemistry. These ring systems can be found in many pharmaceuticals with varied therapeutic applications such as the inhibition of platelet aggregation, treatment of asthma, chronic obstructive pulmonary disorder (COPD), bipolar disorder, psychosis, and prevention of osteoporosis, among many others. ... 

Addition at the C3 position of the thiophene is also possible, although unlikely unless the C2 position is already substituted. The electron-rich thiophene ring prefers electrophilic substitution at the C2 position because the intermediate has greater charge delocalization and, therefore, more stabilization in comparison to the less-favored C3 position. 

Although the electron-rich thiophene may lead to toxicity, the metabolic chemistry of thiophene can also lead to desirable therapeutic effects as in the case of clopidogrel (Plavix). The parent compound is oxidized by cytochrome P-450, and further oxidation in the presence of water... 

Polyfluorenes are an important class of LEP with high thermal, photo and environmental stability and efficient bright blue emission. This stimulated a number of researchers to develop fluorene-thiophene copolymers for light-emitting applications. In addition to an expected increase in PL quantum etSciency, such a combination of electron-rich thiophene units with relatively electron-deficient fluorene units should modify the bandgap of the material (and thus tune the emission) and improve the charge injection/transport balance, compared with fluorene homopolymers. 

As an alternative to catalysis by noble metals, Hu and coworkers [51] developed a nickel/copper-catalyzed direct chemo- and regioselective alkylation of various electron-rich (thiophene) and electron-poor (oxazole and thiazole) heteroarenes with alkyl halides, including those containing a -hydrogen atom (Scheme 19.31). 

Though both Suzuki and Stille reactions have been widely used to prepare conjugated polymers (including D-A copolymers), there are some subtle issues to consider when it comes to choose which reaction to use. For example, it is worth noting that the electron richness of stannyl aromatics decides whether these monomers are suitable for Stille-based polymerization or not. Mechanistically, relatively electron-rich thiophenes undergo the transmetalation step more readily than stannylbenzenes. Thus, stannylbenzenes experience low reactivity under Stille reaction conditions. Correspondingly, most thiophene-based aromatics are polymerized via Stille reactions, whereas a Suzuki reaction is a better option for benzene-based compounds. For example, fluorene and carbazole based polymers are usually prepared by Suzuki reaction, whereas polymers with cyclo-penta[2,l- ) 3,4-6 ]dithiophene, silolo[3,2- 4,5- ) ]dithiophene or benzo[l,2- 4,5-i Jdithiophene are often polymerized via Stille reaction. Due to its broader utilization over the Suzuki reaction in preparing D-A copolymers, Stille reaction-based polymerization will be the focus of this chapter, with a brief discussion on the Suzuki-based polymerization also included (Section 15.2.3). 

Scheme 4.15) [19]. Interestingly, electron-rich thiophenes could also be arylated under similar conditions (Scheme 4.16) [20]. 

Regioselective Direct Arylation of Thiophenes Using Catalyst Control. A cationic Ir-catalyzed direct arylation of electron-rich thiophenes with iodoarenes was disclosed (eq 11). ... 

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