Reduction with triethylsilane/boron trifluoride

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]. 

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... 

Benzyl Alcohols. Benzyl alcohols of nearly all kinds undergo reduction when treated with acid in the presence of organosilicon hydrides. The most obvious exception to this is the behavior of benzyl alcohol itself. It resists reduction by the action of trifluoroacetic acid and triethylsilane, even after extended reaction times.26 Reducing systems consisting of triethylsilane and sulfuric acid/acetic acid or p-toluenesullonic acid/acetic acid mixtures also fail to reduce benzyl alcohol to toluene.134 As previously mentioned, substitution of boron trifluoride for trifluoroacetic acid results in the formation of modest yields of toluene, but only when a very large excess of the silane is used in order to capture the benzyl cation intermediate and suppress Friedel-Crafts oligomerization processes.129,143... 

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... 

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... 

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... 

The reduction of aldehydes with the combination Et3SiH/BF3 OEt2 gives both the alcohol and the symmetrical ether,70 as do the Et3SiH/TFA (and other acids) combinations.313 Addition of boron trifluoride etherate to a mixture of 1-octanal and triethylsilane leads to the formation of di-n-octyl ether in 66% yield and //-octyl alcohol in 34% yield (Eq. 155).74... 

They offer the advantage that reductions can be effected under conditions that permit the conversion of substrates that may be adversely sensitive to the presence of strong Brpnsted acids. For example, in the presence of a 10% excess of triethylsilane, addition of one-half equivalent of boron trifluoride etherate to octanal results, within one hour, in the formation of a 66% yield of dioctyl ether after a basic hydrolytic workup. Benzaldehyde provides a 75% yield of dibenzyl ether under the same reaction conditions. The remainder of the mass is found as the respective alcohol.70 Zinc chloride is also capable of catalyzing this reaction. With its use, simple alkyl aldehydes are converted into the symmetrical ethers in about 50% yields.330... 

Reductive Thiolation. Treatment of aldehydes with triethylsilane, thiols, and boron trifluoride monohydrate 217 yields sulfides in a one-flask process. For example, this method gives a 97% yield of benzyl isopropyl sulfide from benzaldehyde and 2-propanethiol (Eq. 204).365... 

Treatment of a pentacyclic la, I I -(2-oxethano) thioketal steroid with excess Et3SiH/TFA causes reduction of the carbon-carbon double bonds as well as the 17-carbonyl group to give a single reaction product (Eq. 213).368 Other work utilizes trifluoroacetic acid, triethylsilane, and anisole in the presence of a catalytic amount of boron trifluoride etherate to reduce the acetyl carbonyl of a 3-acetyl-2-azetidinone derivative with a dr of 8 1 (Eq. 214).395... 

In a similar way, a mixture consisting of 2% boron trifluoride etherate in trifluoroacetic acid and triethylsilane brings about the regioselective reduction of the acyclic carbonyl group of the diketovinyl chloride shown in Eq. 215 in high yield (>94%), but with formation of approximately equal amounts of the two possible diastereomers formed from the creation of a new chiral center.396... 

A more useful way of reducing esters to ethers is a two-step procedure applied to the reduction of lactones to cyclic ethers. First the lactone is treated with diisobutylaluminum hydride in toluene at —78°, and the product - a lactol - is subjected to the action of triethylsilane and boron trifluoride etherate at —20° to —70°. y-Phenyl-y-butyrolactone was thus transformed to 2-phenyltetrahydrofuran in 75% yield, and 5-lactone of 3-methyl-5-phenyl-5-hydroxy-2-pentenoic acid to 4-methyl-2-phenyl-2,3-dihydropyran in 72% yield [1034]. 

Some reductions that are not possible with triethylsilane and trifluoreacetic acid (5, 695 6, 616) can be effected with triethylsilane and boron trifluoride hydrate. Although benzene, naphthalene, and phenanthrene are not reduced, anthracene and naphthacene are reduced to tetrahydro derivatives in high yield. 1- or 2-Hydroxynaphthalene is reduced to tetralin in moderate yield. ... 

In a useful variant of the classical methylation procedure for linkage analysis in the structural determination of oligo- and poly-sacccharides, the fully methylated oligomer is treated with triethylsilane and boron trifluoride etherate or triethylsilane and trimethylsilyl trifluoromethanesulfonate. This procedure produces partially methylated anhydroalditols. These are acetylated and analyzed by GLC-MS.222 223 This reductive-cleavage method makes possible simultaneous determination of identity, ratio, linkage position, and especially the ring size for each monosaccharide component. 

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 ... 

The reaction of these compounds with triethylsilane and boron trifluoride-etherate is also of interest. Thus, gmelinol (214) gives two products, the major one being (215) (scheme 77) [166]. It is formed by reductive rearrangement of the 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane skeleton. The minor product is a 2-ary 1-4-benzyltetrahydrofuran (216) in... 

A total synthesis of (-)-anisomycin (1) from malimide has been achieved by a highly regio and trans stereoselective reductive alkylation of (S)-M,0-dibenzyl malimide 117 (Scheme 14) [85]. Reductive alkylation of (S)-lM,0-dibenzyl malimide 117, prepared from (S)-malic acid [86], with p-methoxybenzylmagnesium chloride gave the a-hydroxylactam 118 as a di-astereomeric mixture. Hydroxylactam 118 in the presence of 3 equivalents of boron trifluoride etherate was reduced with excess of triethylsilane to yield predominantly trans-119 in 94.8% yield. Catalytic hydrogenation of 119 afforded 120 in quantitative yield which was reduced to pyrrolidine 121 in 90%... 

Reductive Etherifications and Acetal Reductions. Additional applications of triethylsilane in the reduction of C-0 bonds also continue to surface. The Kusanov-Pames dehydrative reduction of hemiacetals and acetals with trifluorosulfonic acid/EtsSiH has proven especially valuable. Under such conditions, 4,6-O-benzyli-dene acetal glucose derivatives can be asymmetrically deprotected to 6-0-benzyl-4-hydroxy derivatives (eq 28) and thioketone derivatives can be converted to syn-2,3-bisaryl (or heteroaryl) di-hydrobenzoxanthins with excellent stereo- and chemoselectivity (eq 29). Triethylsilane is also useful in a number of related acetal reductions, including those used for the formation of C-glycosides. For example, EtsSiH reductively opens 1,3-dioxolan-4-ones to 2-alkoxy carboxylic acids when catalyzed by HCU. Furthermore, functionalized tetrahydrofurans are generated in good yield from 1,2-0-isopropylidenefuranose derivatives with boron trifluoride etherate and EtsSiH (eq 30). These same conditions lead to 1,4- or 1,5-anhydroalditols when applied to methyl furanosides or pyranosides. ... 

A new method of D-glucan analysis involves reductive cleavage of permethylated compounds with triethylsilane and trimethylsilyl triflate or boron trifluoride-etherate as catalyst, followed by acetylation, which yields a series of acetylated, methylated 1,5-anhydro-glucitols. A number of isomeric substituted 1,5-anhydro-glucitols were synthesized as references. /3-Glycosyl-... 

Fig. 4.42. Reductive depolymerization of a permethylated galactomannan (according to Kiwitt-Haschemie et al., 1996) 1. Reductive cleavage with triethylsilane and trimethylsilylmethanesulfonate/boron trifluoride 2. Acetylation with acetic anhydride and N-methylimidazole...

The regioselective reductive-cleavage of the galactose-glucose link in die sialic acid containing trisaccharide derivative 7 with borane-dimethylsulfide complex in the presence of boron trifluoride or by triethylsilane afforded anhydro derivative 8."... 

Derivative 61 was synthesized in 71% yield by reductive bond cleavage of the corresponding 4,6-0-o-nitrobenzylidene acetal of methyl 3,4-acetyl- 5-glucoside with triethylsilane and boron trifluoride ether-ate, followed by deacetylation of the 3,4-diacetates with sodium methoxide in methanol. 

---