Hydrogenations ionic, triethylsilane

Benzylic or allylic oxygen functions react with Lewis acids such as trifluoroacetic acid to generate allyl or benzylic cations which abstract a hydride from silanes such as triethylsilane 84 b to result in the removal of the oxygen function in a process which has been called ionic hydrogenation and which has been reviewed [34-38]. 

Trisubstituted Alkenes. With very few exceptions, trisubstituted alkenes that are exposed to Brpnsted acids and organosilicon hydrides rapidly undergo ionic hydrogenations to give reduced products in high yields. This is best illustrated by the broad variety of reaction conditions under which the benchmark compound 1-methylcyclohexene is reduced to methylcyclohexane.134 146,192 202 203 207-210 214 234 When 1-methylcyclohexene is reduced with one equivalent of deuterated triethylsilane and two equivalents of trifluoroacetic acid at 50°, methylcyclohexane-... 

Exceptions to the generally facile ionic hydrogenation of trisubstituted alkenes include the resistance of both 2-methyl-1-nitropropene (R = NO2) and 3,3-dimeth-ylacrylic acid (R = CO2H) to the action of a mixture of triethylsilane and excess trifluoroacetic acid at 50° (Eq. 85).234 The failure to undergo reduction is clearly related to the unfavorable effects caused by the electron-withdrawing substituents on the energies of the required carbocation intermediates. 

Reduction of dienes incorporated into steroid structures may lead to different configurations in the products. For example, treatment of 8(9),14(15)-bisdehydroestrone 42 (R = H) for four hours at room temperature with twenty equivalents of trifluoroacetic acid and two equivalents of triethylsilane leads to an ionic hydrogenation product mixture containing the natural 8/1,9a,14a-estrone 43 as a minor component (11%) and the 8a,9/i, l 4/i-isomcr 44 as the major component (83%) (Eq. 92).241 The related methyl ether (42, R = Me) behaves in a similar fashion.241 The yield of natural isomer 46 formed from the methyl ether of A8(9),i4(i5)-bigdehydroestradiol analog 45 increases from 22 to 34%, and that of... 

Homoconjugation results in enhanced reactivity of substrates toward ionic hydrogenation. Bicyclo[2.2.1]hepta-2,5-diene forms a mixture of the trifluoroac-etate esters of bicyclo[2.2.1]hepten-2-ol, tricyclo[2.2.1.02 6]heptan-3-ol, and bicyclo[2.2.1]heptan-2-ol in a 62 20 17 ratio on treatment with 10 equivalents of triethylsilane and 20 equivalents of trifluoroacetic acid for 24 hours at room temperature (Eq. 96), 230... 

Based on the few reported examples, the pattern of ring cleavage that accompanies the ionic hydrogenation of alkylidenencyclopropanes seems to be related to the pattern and degree of substitution on both the ring and the double bond.233 Thus, treatment of l,l-dimethyl-2-methylenecyclopropane with two equivalents of triethylsilane and four equivalents of trifluoroacetic acid for 90 hours at room temperature yields 65% of 2,3-dimethylbutane (Eq. 114).229 Exposure of 1,1-dimethyl-2-isopropylidenecyclopropane to the same ratio of reactants at 50° for 16 hours produces a complex mixture containing 63% of 2,5-dimethylhexane, 18.5% of 2,5-dimethyl-3-hexene, 1.6% of 2,5-dimethyl-2-hexene, and 7% of 2,5-dimethyl-2-hexyl trifluoroacetate (Eq. 115).229... 

Ionic hydrogenations of C=C and C=0 bonds were reported prior to the development of ionic hydrogenations mediated or catalyzed by transition metals. Tri-fluoroacetic acid (CF3C02H) as the proton donor and triethylsilane (HSiEt3) as the hydride donor are most commonly used, though a variety of other acids and several other hydride donors have also been shown to be effective. A review [1] by Kursanov et al. of the applications of ionic hydrogenations in organic synthe-... 

The furoindole 70 is selectively reduced in high yield to the corresponding unstable, air-sensitive furoindoline 71 by ionic hydrogenation with triethylsilane in trifluoroacetic acid (TEA) (Equation 11) <20010L1343>. 

Unsaturated ketonucleosides have been shown to be remarkably stable under acidic conditions. 7-(3-0-Acetyl-4,6-dideoxy-/ -L-g/t/cm>-hex-3-enopyranosyl-2-ulose)theophylline (61a) proved to be stable in 0.1 M hydrochloric acid, as no glycosylic cleavage had occurred51 after 20 h. Similarly, no decomposition was observed when 7-(3,6-di-0-ace-tyl-2-deoxy-/ -D-gh/cero-hex-2-enopyranosyl-4-ulose)theophylline (66) was treated with 0.1 M sulfuric acid during 48 h at room temperature, and attempted, ionic hydrogenation with triethylsilane - trifluoroacetic acid failed.31... 

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... 

Trifluoroacetic acid deprotection. Trialkylsilanes in combination with an acid as a hydride donor are useful for ionic hydrogenation. DuPont chemists recommend triethyl- or triisopropylsilane as scavengers for carbocationic by-products formed in TFA deprotection of amino acids. In fact, triethylsilane can be more effective than ethanedithiol, a commonly used scavenger. 

Direct reductive elimination of the hydroxyl group can be achieved readily only for tertiary and benzylic alcohols, which are especially liable to form carbocationic intermediates in acidic media. These intermediates are able to abstract hydrogen from such hydride donors as triethylsilane. This procedure, ionic hydrogenation, was elaborated into a preparatively useful protocol ... 

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%). ... 

If other reactive moieties are present a cyclopropanecarbonyl compound can be converted to the corresponding cyclopropylalkane using various conditions. Thus, 3,4-benzotricy-clo[4.3.1.0 ]dec-3-en-2-one yielded 3,4-benzotricyclo[4.3.1.0 ]dec-3-ene in excellent yield on treatment with sodium in liquid ammonia. di-l-Methylcyclopropane-l,2-dicarboxylic anhydride underwent a similar reaction to afford isomeric lactones on treatment with lithium aluminum hydride or sodium borohydride in tetrahydrofuran. On the other hand, ionic hydrogenation (triethylsilane in trifluoroacetic acid and water) of cyclopropyl phenyl ketone gave a complex reaction mixture and very little benzylcyclopropane. ... 

Some dihydro-Reissert analogs have been prepared in this series. Thus, catalytic hydrogenation of 93 under very mild conditions or an ionic hydrogenation of 92 using triethylsilane and trifluoroacetic acid gives 97 and 98, respectively. The dihydro analog 98 has also been prepared from... 

As with the similarly polarized boron and aluminium hydrides, hydrido-silanes can transfer formal hydride ions to electropositive carbon centres. Unlike the first two reducing agents, hydridosilanes require additional activation of the carbon centre by Lewis or protic acids before such hydride transfer can take place. This overall process is known as ionic hydrogenation (4). The reagent system of triethylsilane and boron trifluoride etherate has provided an extremely selective method for the reductive deoxygenation of lactols (5), derived in turn from DIBAL reduction (6) of the corresponding y- or 6-lactones ... 

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 with silanes can be accomplished in the presence of an acid or Lewis acid. For example, a combinahon of triethylsilane and trifluoroacetic acid (TFA) provides a non-catalyhc method for hydrogenahon of C=C, C=0 and C=N double bonds and for hydrogenolysis of some single bonds (such as C—Br or benzylic C—OH). Alkenes can be reduced to saturated hydrocarbons, but only if the double bond is at least trisubstituted, allowing the possibility of selechve hydrogenahon in a compound containing different types of double bond. A useful... 

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... 

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). 

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