Reductive with triethylsilane

Alkyl iodides, benzyl chlorides, benzyl bromides, and adamantyl bromides and iodides undergo reduction with triethylsilane/palladium chloride.195 The reduction of a /3-chloro ether occurs in excellent yield with this system (Eq. 56).195... 

For the reduction of aliphatic ketones to hydrocarbons several methods are available reduction with triethylsilane and boron trifluoride [772], Clemmensen reduction [160, 758] (p. 28), Wolff-Kizhner reduction [280, 281, 759] (p. 34), reduction of p-toluenesulfonylhydrazones with sodium borohydride [785], sodium cyanoborohydride [57i] or borane [786] (p. 134), desulfurization of dithioketals (jaeicaipioles) [799,823] (pp. 130,131) and electroreduction [824]. 

A reduction with triethylsilane, which is a pure SN1 reaction, is familiar from Figure 17.62, namely as the second step of a two-step reduction of a carboxylic acid ester to a simple ether via an oc-acetoxyether. 

Cyclic diene ether 93 underwent oxidative acetalization to produce corresponding 3-substituted acetals 100 and 101 (Scheme 17) <1995TL8263>. Further Lewis acid-catalyzed reduction with triethylsilane afforded corresponding 3-bromo- and 3-hydroxy-oxonenes (102 R = Br (68%) 103 R = OH (49%), respectively) together with 1 1 diastereomeric mixture of acyclic methyl ethers 104 (R = Br (18%) R = OH (13%)). 

Oxidative fluorodesulfurization can also be achieved by the action of nitrosonium tetrafluo-roborate, as oxidant, and hydrogen fluoridc/pyridine, as a source of fluoride ions, on aryl sulfides.249 The starting compounds are easily prepared from ketones or aldehydes and ben-zenethio) using boron trifluoride monohydrate as catalyst, and subsequent reduction with triethylsilane.249 250... 

Reduction with Triethylsilane allows for the formation of enantiomerically pure 5-substituted pyrrolidinones and 2-substituted pyrrolidines in the same manner. ... 

The conversion of oc,p-unsaturated esters into saturated esters proceeds by selective reduction with triethylsilane in the presence of Wilkinson catalyst - or by hydrogenation using 5-10% Pd/C in... 

Vilsmeier reaction to the chloroaldehyde (106), followed by reductive meth-ylation, yielded the aldehyde 107 (Scheme 14) with the precedented stereochemical outcome. Attempted halogenation of the derived neopentyl-type alcohol was unsuccessful under a variety of conditions, so an alternative scheme involving two successive Wittig-type reactions was developed. The aldehyde 107 was converted to the unsaturated aldehyde 108 by the method of Nagata and Hayase. Reduction with triethylsilane and tris (triphenylphosphine) rhodium chloride was followed by condensation with isopropylidene phosphorane to give the desired product 109. 

On reacting aldehydes such as benzaldehyde or cyclohexanecarboxaldehyde 720 with silylated alcohols such as 718 or 721, or with triethylsilane 84b in the presence of TMSOTf 20 at low temperatures, acetal formation and reduction is achieved in one step to afford ethers 719 and 722 in high yields [215] (Scheme 5.74). 

With TMSOTf 20 as catalyst instead, reduction of acetals or ketals has also been achieved with triethylsilane 84b in the presence of triflic acid/BSA 22a [56] or with triethylsilane 84b/Nafion-H, which can be readily recovered [57]. 

Oriyama and coworkers reported an iron-catalyzed reductive etherification of carbonyl compounds with triethylsilane and alkoxytriaUcylsilane [149, 150] and alcohols (Scheme 48) [151]. 

The reduction of 2-(hydroxymethyl)-l,4,6,8-tetramethylazulene to 1,2,4,6,8-pentamethylazulene occurs quantitatively upon treatment with triethylsilane and trifluoroacetic acid at 60° for 19 hours (Eq. 22).163... 

A variety of para-substituted 2-phenyl-2-butanols undergo quick and efficient reductions to the corresponding 2-phenylbutanes when they are dissolved in dichloromethane and a 2-10% excess of phenylmethylneopentylsilane and boron trifluoride is introduced at 0° (Eq. 30).126 Several reactions deserve mention. For example, when R = CF3, use of trifluoroacetic acid produces no hydrocarbon product, even after two hours of reaction time. In contrast, addition of boron trifluoride catalyst provides an 80% yield of product after only two minutes. When R = MeO, both trifluoroacetic acid and boron trifluoride produce a quantitative yield of the hydrocarbon within two minutes. However, when R = NO2, attempts to promote the reduction with either trifluoroacetic acid or even methanesulfonic acid fail even after reaction periods of up to eight hours, only recovered starting alcohol is obtained. Use of boron trifluoride provides a quantitative conversion into 2-(/ -nitrophenyl)butane after only ten minutes. It is significant that the normally easily reducible nitro group survives these conditions entirely intact.126129 Triethylsilane may be used as the silane.143... 

Intramolecular Friedel-Crafts reactions can sometimes compete with organosil-icon hydride reductions of benzylic-type alcohols to cause formation of undesired products. An example is the attempted reduction of alcohol 26 to the corresponding hydrocarbon. When 26 is treated with triethylsilane in trifluoroacetic acid at room temperature for 15 hours, a mixture of the two fluorene isomers 27 and 28 is obtained in a combined yield of 45%. None of the hydrocarbon structurally related to the substrate alcohol 26 is obtained.171 Whether this problem could be circumvented by running the reduction at a lower temperature or with a different acid remains subject to experimentation. 

Treatment of l-[2-(2-methoxy-5-isopropylphenyl)-l-hydroxyethyl]-2,6,6-tri-methylcyclohexene with triethylsilane and boron trifluoride etherate in dichloro-methane at —10° leads to its reduction to 2-(2,6,6-trimethyl-l-cyclohexenyl)-l-(2-methoxy-5-isopropylphenyl)ethane in 69% yield (Eq. 36).174... 

Highly diasteroselective and chemoselective reductions may be performed on the hydroxy functions of (r/6-arene)-tricarbonylchromium complexes. Treatment of the chromium-complexed benzylic alcohol 29 with triethylsilane and boron trifluoride etherate in dichloromethane at —78° to 0° gives only diastereomer 30 in 75% yield (Eq. 40).181 In a similar fashion, treatment of the complexed exo-allyl-endo-benzylic alcohol 31 with an excess of Et3SiH/TFA in dichloromethane at room temperature under nitrogen produces only the endo-aflyl product 32 in 92% yield after 1.5 hours (Eq. 41). It is noteworthy that no reduction of the isolated double bond occurs.182... 

The use of a deuterium-labeled organosilicon hydride and location of the deuterium isotope in the reduced product shows that 1,2-hydride shifts also occur. Thus, reduction of 1-bromohexane with triethylsilane-A yields hexane with all of the deuterium at C2 (Eq. 51) similar treatment of cyclohexylmethyl bromide produces melhyIcyclohexane-1 -di (Eq. 52).186... 

Trialkylsilanes are generally more effective than dialkyl- or monoalkylsilanes in minimizing isomerizations. The reduction of 2-bromododecane to dodecane proceeds under aluminum chloride catalysis in 82% yield using n-butylsilane and in 87% yield with tri-n-butylsilane.186 However, similar treatment of bromo-cycloheptane with triethylsilane yields a mixture of 39% cycloheptane and 26% methylcyclohexane. The same substrate yields 65% methylcyclohexane and less than 1% cycloheptane when n -butylsilane is the reducing agent.186... 

Bromoadamantane and 1-bromoadamantane are reduced to adamantane in yields of 84% and 79%, respectively, when treated with triethylsilane and catalytic amounts of aluminum chloride.186 Similar treatment of benzhydryl chloride and exo-2-bromonorbomane gives the related hydrocarbons in yields of 100% and 96%, respectively.186 In contrast, 2-bromo-l-phenylpropane gives only a 43% yield of 1-phenylpropane the remainder consists of Friedel-Crafts alkylation products.186 Some alkyl halides resist reduction by this method, even when forcing conditions are employed. These include p-nitrobenzyl bromide, 3-bromopropanenitrile, and 5-bromopentanenitrile.186... 

The reduction of 4-chloro-4-methyltetrahydropyran with triethylsilane requires more than a catalytic amount of aluminum chloride. No 4-methyltetrahydropyran is obtained after 20 hours at room temperature even when 0.75 equivalents of the catalyst is used, but a 92% yield is obtained after only 30 minutes when two equivalents of catalyst and three equivalents of triethylsilane are used.136 146 This is presumably a result of the ability of the Lewis acid to coordinate at the ring oxygen as well as at the chlorine. The introduction of alkyl groups at C2 appears to introduce enough steric hindrance near the ring oxygen to enable less than one equivalent of aluminum chloride to effect reduction, but also makes the products unstable to the reaction conditions so that the synthetic yields decline compared with the unsubstituted substrate.136... 

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... 

Vinyl and Aryl Halides and Triflates. The organosilane reduction of aryl halides is possible in high yields with triethylsilane and palladium chloride.195 The reaction is equally successful with aryl chlorides, bromides, and iodides. Aryl bromides and iodides, but not chlorides, are reduced with PMHS/Pd(PPh3)4 in moderate to excellent yields.199 This system also reduces vinyl bromides.199 p-Chlorobenzophenone is reduced to benzophenone with yym-tetramethyldisilo-xane and Ni/C in excellent yield (Eq. 59).200 There is a report of the organosilane reduction of aryl and vinyl triflates in very high yields with the combination of Et3SiH/Pd(OAc)2/dppp (l,3-bis(diphenylphosphino)propane) (Eq. 60).201... 

Monosubstituted Alkenes. Simple unbranched terminal alkenes that have only alkyl substituents, such as 1-hexene,2031-octene,209 or ally Icy clohexane230 do not undergo reduction in the presence of organosilicon hydrides and strong acids, even under extreme conditions.1,2 For example, when 1-hexene is heated in a sealed ampoule at 140° for 10 hours with triethylsilane and excess trifluoroacetic acid, only a trace of hexane is detected.203 A somewhat surprising exception to this pattern is the formation of ethylcyclohexane in 20% yield upon treatment of vinylcyclohexane with trifluoroacetic acid and triethylsilane.230 Protonation of the terminal carbon is thought to initiate a 1,2-hydride shift that leads to the formation of the tertiary 1-ethyl-1-cyclohexyl cation.230... 

Surprisingly, a-cyanoacrylic acid is reported to react spontaneously with triethylsilane in the absence of any additional acid to give a quantitative yield of the triethylsilyl ester of a-cyanopropionic acid.236 Ethyl a-cyanoacrylate requires the presence of trifluoroacetic acid to undergo reduction to ethyl 2-cyanopropionate.236 Many of these reductions are highly stereoselective. For example, treatment of... 

The reduction of A9(10)-octalin to cis- and /ran.v-decalins occurs with cis to trans stereoselectivities that vary with the nature of the organosilicon hydride employed. The ratios are 0.28-0.59 with n-butylsilane, 0.67 with diethylsilane,204 0.34212 or 0.72204 with triethylsilane, 0.67 with diphenylsilane, 0.77 with diphen-ylmethylsilane,212 1.3 8204—1.80127,212 with triphenylsilane, 0.54 with triisopen-tylsilane, 1.17 with tricyclopentylsilane, 2.57 with tri-.vcc-bulylsilane, 3.35 with di-ferf-butylsilane, 4.88 with di-ferf-butylmethylsilane, and 13.3 with tri-rm-butylsilane.204 Opinions differ about the mechanistic significance of these changes in isomer ratios.204,212... 

Partial reduction of polyarenes has been reported. Use of boron trifluoride hydrate (BF3 OH2) as the acid in conjunction with triethylsilane causes the reduction of certain activated aromatic systems 217,262 Thus, treatment of anthracene with a 4-6 molar excess of BE3 OH2 and a 30% molar excess of triethylsilane gives 9,10-dihydroanthracene in 89% yield after 1 hour at room temperature (Eq. 120). Naphthacene gives the analogously reduced product in 88% yield under the same conditions. These conditions also result in the formation of tetralin from 1-hydroxynaphthalene (52%, 4 hours), 2-hydroxy naphthalene (37%, 7 hours), 1-methoxynaphthalene (37%, 10 hours), 2-methoxynaphthalene (26%, 10 hours), and 1-naphthalenethiol (13%, 6 hours). Naphthalene, phenanthrene, 1-methylnaphthalene, 2-naphthalenethiol, phenol, anisole, toluene, and benzene all resist reduction under these conditions.217 Use of deuterated triethylsilane to reduce 1-methoxynaphthalene gives tetralin-l,l,3-yielding information on the mechanism of these reductions.262 2-Mercaptonaphthalenes are reduced to 2,3,4,5-tetrahydronaphthalenes in poor to modest yields.217 263... 

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