Triethylsilane hydrogenations with

A mixture of exo- and endo-isomers of 5-methylbicylo[2.2.1]hept-2-ene is hydrogenated with the aid of five equivalents of triethylsilane and 13.1 equivalents of trifluoroacetic acid to produce a 45% yield of < <7o-2-methylbicylo[2.2.1] heptane (Eq. 71). The same product is formed in 37% yield after only five minutes. The remainder of the reaction products is a mixture of three isomeric secondary exo-methylbicylo[2.2.1]heptyl trifluoroacetates that remains inert to the reaction conditions. Use of triethylsilane-l-d gives the endo-2-methylbicylo-[2.2.1]heptane product with an exo-deuterium at the tertiary carbon position shared with the methyl group. This result reflects the nature of the internal carbocation rearrangements that precede capture by the silane.230... 

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... 

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%). ... 

An efficient two-step procedure for the A -methylation of amides (equation 19) involves the preparation of intermediate methylols with subsequent reduction using triethylsilane, hydrogen/Pd-C or cyanoborohydride. ... 

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... 

Tin tetrachloride has been used to prepare the stericaHy hindered triisopropylchlorosilane [13154-24-0] (119). Organobromosdanes are obtained under similar conditions through reaction with cupric and mercuric bromide. These reactions are most suitable for stepwise displacement of hydrogen to form mixed hydridochlorosilanes or in systems sensitive to halogen (120). Hydrides have also been displaced using organic bromides. Heating triethylsilane and... 

For the acetoxy radical, the for decarboxylation is about 6.5 kcal/mol and the rate is about 10 s at 60°C and 10 s at —80°C. Thus, only very rapid reactions can compete with decarboxylation. As would be expected because of the lower stability of aryl radicals, the rates of decarboxylation of aroyloxy radicals are slower. The rate for p-methoxybenzoyloxy radical has been determined to be 3 x 10 s near room temperature. Hydrogen donation by very reactive hydrogen-atom donors such as triethylsilane can compete with decarboxylation at moderate temperatures. 

The low reactivity of alkyl and/or phenyl substituted organosilanes in reduction processes can be ameliorated in the presence of a catalytic amount of alkanethiols. The reaction mechanism is reported in Scheme 5 and shows that alkyl radicals abstract hydrogen from thiols and the resulting thiyl radical abstracts hydrogen from the silane. This procedure, which was coined polarity-reversal catalysis, has been applied to dehalogenation, deoxygenation, and desulfurization reactions.For example, 1-bromoadamantane is quantitatively reduced with 2 equiv of triethylsilane in the presence of a catalytic amount of ferf-dodecanethiol. 

Aldehydes and ketones can be converted to ethers by treatment with an alcohol and triethylsilane in the presence of a strong acid or by hydrogenation in alcoholic acid in the presence of platinum oxide. The process can formally be regarded as addition of ROH to give a hemiacetal RR C(OH)OR", followed by reduction of the OH. In this respect, it is similar to 16-14. In a similar reaction, ketones can be converted to carboxylic esters (reductive acylation of ketones) by treatment with an acyl chloride and triphenyltin hydride. " ... 

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]. 

Aluminum chloride, used either as a stoichiometric reagent or as a catalyst with gaseous hydrogen chloride, may be used to promote silane reductions of secondary alkyl alcohols that otherwise resist reduction by the action of weaker acids.136 For example, cyclohexanol is not reduced by organosilicon hydrides in the presence of trifluoroacetic acid in dichloromethane, presumably because of the relative instability and difficult formation of the secondary cyclohexyl carbocation. By contrast, treatment of cyclohexanol with an excess of hydrogen chloride gas in the presence of a three-to-four-fold excess of triethylsilane and 1.5 equivalents of aluminum chloride in anhydrous dichloromethane produces 70% of cyclohexane and 7% of methylcyclopentane after a reaction time of 3.5 hours at... 

Tertiary Alkyl Alcohols. Tertiary alkyl alcohols generally undergo facile reduction when treated with acids in the presence of organosilicon hydrides.127,136 This comparative ease of reduction reflects the enhanced stability and ease of formation of tertiary alkyl carbenium ions compared with primary and secondary carbenium ions. Thus, treatment of 1-methylcyclohexanol with mixtures of triethylsilane and aluminum chloride in dichloromethane produces near quantitative yields of methylcyclohexane with or without added hydrogen chloride in as little as 30 minutes at room temperature, in contrast to the more vigorous conditions needed for the reduction of the secondary alcohol cyclohex-anol.136... 

Treatment with triethylsilane and boron trifluoride etherate allows a variety of methyl (i-hydroxy-/3-ary lpropionates to be reduced to methyl ft -ary lpropionates in yields of 85-100% as part of a synthetic sequence leading to the preparation of indanones (Eq. 31).170 Small amounts of dehydration products formed simultaneously are reduced to the methyl -arylpropionates by mild catalytic hydrogenation.170... 

It is clear that the ionizing power of the solvent used is important in many of these reductions. When 2,4,6-trimethylbenzyl chloride is heated with diphenylsi-lane in nitrobenzene at temperatures as high as 130°, no isodurene is formed.193 Not unexpectedly, the same lack of reactivity is reported for a series of benzyl fluorides, chlorides, and bromides substituted in the para position with nitro or methyl groups or hydrogen when they are heated in nitrobenzene solutions with triethylsilane, triethoxy silane, or diphenylsilane.193... 

Unlike cyclohexene, its oxa analog, 3,4-dihydro-2//-pyran, undergoes facile reduction to tetrahydropyran in yields ranging from 70 to 92% when treated with a slight excess of triethylsilane and an excess of either trifluoroacetic acid or a combination of hydrogen chloride and aluminum chloride (Eq. 69).146 This difference in behavior can be understood in terms of the accessibility of the resonance-stabilized oxonium ion intermediate formed upon protonation. 

Preferential protonation of oxygen in comparison to carbon prevents 4-methyl-enetetrahydropyran from undergoing reduction to 4-methyltetrahydropyran even when held at 70° for 10 hours in the presence of triethylsilane and a 20-fold excess of trifluoroacetic acid.146 However, when the reaction conditions are changed so that a dichloromethane solution of the same substrate is treated with a mixture of four equivalents of triethylsilane and three equivalents of aluminum chloride in the presence of excess hydrogen chloride, a 40% yield of 4-methyltetrahydropyran product is obtained at room temperature after one hour (Eq. 75).136... 

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-... 

Hydrogenation of the carbon-carbon double bond occurs without alteration of the ester function when citronellyl acetate is treated with 2.5 equivalents of trifluoroacetic acid and two equivalents of triethylsilane in 2-nitropropane.205 The reduced product is obtained in 90% yield after 22 hours at room temperature in the presence of one equivalent of added lithium perchlorate (Eq. 82). The yields are lower in the absence of this added salt. Similar reduction of an unsaturated phenolic chroman derivative occurs to give an 85% yield of product with only the carbon-carbon double bond reduced (Eq. 83).205... 

A dichloromethane solution of 4 - m e th y I - 5,6 - d i hy dro - 2 // -pyran gives 4-me-thyltetrahydropyran in 35% yield when treated with a mixture of five equivalents of triethylsilane and 2.5 equivalents of aluminum chloride in the presence of excess hydrogen chloride at room temperature for one hour (Eq. 84).136 This behavior is essentially the same as that exhibited by the disubstituted 4-methylenetetrahydropyran isomer under similar conditions.136... 

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... 

The use of stronger acid conditions provides somewhat better synthetic yields of alkanes from alkynes. A useful method consists of treatment of the substrate with a combination of triethylsilane, aluminum chloride, and excess hydrogen chloride in dichloromethane.146 Thus, treatment of phenylacetylene with 5 equivalents of triethylsilane and 0.2 equivalents of aluminum chloride in this way at room temperature yields 50% of ethylbenzene after 1.5 hours. Diphenylacetylene gives a 50% yield of bibenzyl when treated with 97 equivalents of triethylsilane and 2.7 equivalents of aluminum chloride after 2.8 hours. Even 1-hexyne gives a mixture of 44% n -hexane and 7% methylpentane of undisclosed structure when treated with 10 equivalents of triethylsilane and 0.5 equivalent of aluminum chloride for 0.5 hour.146... 

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... 

The silylation of benzylic G-H bonds is achieved by using Ru3(GO)12 catalyst in the presence of norbornene as a hydrogen acceptor.145 The reaction of 2-(2,6-dimethylphenyl)pyridine with triethylsilane in the presence of Ru3(CO)i2 catalyst and norbornene affords mono- and disilylation products in 30% and 55% yields, respectively (Equation (106)). The reaction of 2-(2-tolyl)pyridine shows that the silylation of the aromatic C-H bond is more facile than that of the benzylic C-H bond. 

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