Ionic hydrogenation thiophenes

The so-called ionic method for hydrogenating thiophenes (78T1703) is a further illustration of the chemical consequences of protonation. Protonation of the thiophene ring renders the ring susceptible to hydride ion attack, conveniently derived from triethylsilane (Scheme 12). 

Thiophenes are best converted to the tetrahydro derivatives by the so-called ionic hydrogenation. This depends on the successive addition of a proton (from trifluoroacetic acid) and a hydride ion (from triethylsilane) (75T311). A subsequent improvement involved the use of HC1/A1C13 to form the thiophenium ion and then reaction with triethylsilane (78T1703) best results are obtained with the substrate/Et3SiH/AlCl3 ratio of 1 3 0.3. The mechanism of the reaction is shown in Scheme 43. Evidence for this has been provided by the use of Et3SiD, when D enters positions 3 and 5 in the product. 

Synthesis of standards. Friedel-Crafts acylation of 2,3-dimethylthiophene with hexadecanoic acid and a subsequent reduction of the ketone with LiAlD4 yielded the 2,3-dimethyl-5-(l ,l -d2-hexadecyl)thiophene (II, Table II). Experimental details of these reactions have been reported elsewhere (10). Ionic hydrogenation of the 2,3-dimethyl-5-(l ,l -d2-hexadecyl)thiophene in trifluoroacetic acid using triethylsilane and BF3.etherate as catalyst yielded 2,3-dimethyl-5-(l ,l -d2-hexadecyl)thiolane (IV, Table II). For... 

Ionic hydrogenation of thiophenes and some other heterocycles... 

Thiophenium ions not only play a key role in electrophilic substitution reactions but they also allow some addition reactions to be possible, such as the ionic hydrogenation of thiophene derivatives proceeding by repeated protonations and additions of hydride ion (Scheme 16) (73IZV1918, 75T311, 78T1703, 79MI1). 

Ionic hydrogenation is also described for indole, carbazole and furan derivatives (79MI1). However, it is most important for thiophenes since the latter are well known as poisons for most hydrogenation catalysts. 

A very convenient and versatile new reduction method, which has been intensively studied for the reduction of thiophenes (vide infra), makes use of the combination of a trialkylsilane and an acid, usually trifluoroacetic acid (TFA). This so-called ionic hydrogenation provides a novel reduction of furans to tetrahydrofurans (Scheme 3). Although Bolestova et al. find that the conditions are critical in order to avoid polymerization, the yields of tetrahydrofurans can be quite good. The reduction is accelerated by the presence of boron trifluoride etherate but fails with carbonyl-substituted furans, such as methyl pyro-mucate. ... 

An extremely powerful and efficient new reduction of thiophenes to tetrahydrothiophenes involves ionic hydrogenation with a trialkylsilane and an acid. Typically, a mixture of triethylsilane and trifluo-roacetic acid is employed (equations 26 and 27). This reduction is reasonably general, although thiophene itself is poorly reduced (equation 26) and 2,5-diphenylthiophene is inert to these conditions. Not surprisingly, 2-benzoylthiophene is converted to 2-benzyltetrahydrothiophene (75%). ... 

For this ionic hydrogenation of thiophenes, Kursanov and coworkers have proposed the pathway shown in Scheme 4, based on the labeling results obtained for the reduction of 2,5-dimethylthiophene. ... 

This ionic hydrogenation can be improved by the addition of either boron trifluoride etherate or certain salts and acids. Furthermore, a more powerful set of conditions involving EtsSiH and HCl-AlCb has been used to reduce thiophenes that are recalcitrant under the usual EtaSiH/TFA conditions (equations 28 and 29). In fact, the intermediate salt (14) can be isolated. 

In a process that is related to the ionic hydrogenation method discussed above, Wristers has discovered that the unusual combination of H2/isopentane/HF/TaFs reduces thiophene to tetrahydrothiophene in 80% yield. These conditions also reduce dibenzothiophene to hexahydrodibenzothiophene. It has also been reported that Zn/TFA reduces thiophenes to 2,5-dihydrothiophenes (equations 31 and 32). However, both acetic acid and HCl/benzene are ineffective with zinc in this regard. ... 

Thiophen Analogues of Steroids.— The ketone (141) was condensed with 2-(carbethoxymethyl)piperidine to give the 10-aza-l7-thia-steroid (142). With 4-oxo-4,5,6,7-tetrahydrobenzo[6]thiophen and 2-methyI-3-oxothiophen 1,1-dioxide as the precursors of rings a and B, and D, respectively, (143) was synthesized ionic hydrogenation of the 8,14-diene derived from (143) resulted... 

Ionic hydrogenation has been referred to in CHEC-I <84CHEC-I(4)741>. Logically, this has to find a place in this section, since it represents reaction of a thiophenium ion with a hydride ion derived from triethylsilane. This has been reviewed <85HC(44/i)457>. Reduction of 5-hydroxy-benzo[ >]thiophene with triethylsilane in TEA has given the 2,3-dihydroderivative <91SC959>. 

Ionic hydrogenation of 2-methyl-2,3-dihydrothieno[2,3-Z)]-thiophene (262) affords cw-2,8-dithiabicyclo[3.3.0]octane (263) (79MI1). 

Various thiolans have been prepared by ionic hydrogenation of thiophens with EtjSiH in the presence of acids. Addition of singlet oxygen to alkyl-substituted thiophens, followed by reduction with di-imine, gave the bicyclic compounds (42) these are examples of the hardly known thia-ozonides. 9-Thia-noradamantane (43) has been synthesized from cyclo-octa-2,7-dienone by a reaction sequence involving a transannular C—H carbene insertion. A bicyclic product (44) has been obtained by the reaction of (—)-carvone with... 

Keywords Birch reduction Diels-Alder reaction Dienes Dienophiles Dimerization Ionic hydrogenation Oxidation Reduction Reductive desulfurization Thiophene 1,1-dioxides Thiophene 1-oxides Transition metal complexes... 

Scheme 111 The general mechanism of ionic hydrogenation of thiophenes [126, 127] Table 2 Ionic hydrogenation of thiophenes with CF3CO2H HSiEts...

Benzo[h]thiophene itself reacts slowly under ionic hydrogenation conditions to give 2,3-dihydrobenzo[h]thiophene, whereas 2-alkyl or 3-alkyl benzo[( ]thiophenes are readily reduced. As shown in Table 3, the ionic hydrogenation of... 

Tables Ionic hydrogenation of benzo[h]thiophenes with CF3C02HHSiEt3...

Table 4 Ionic hydrogenation of thiophene with CFjCOiH-Zn...

The ionic hydrogenation of thiophens with a mixture of triethylsilane and trifluoroacetic acid, consisting of electrophilic protonation followed by hydride addition, has been used for the synthesis of (109) from (110) and of the tetra-hydrothiophen derivative (111) from the corresponding thiophen. Also, a series of 2-(co-diethylaminoalkyl)thiophens (112) has been hydrogenated with... 

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