Reductions triethylsilane

The TFA-catalyzed triethylsilane reductive condensation of an aldehyde with indoles provides a convenient route to 3-substituted indoles in modest to good yields (Eq. 197).355... 

The triethylsilane reduction of the alkylidene-l,3-dione 78 occurs fashion at the acyclic carbonyl group (Eq. 267).396 in a 1,2-... 

The triethylsilane reduction of the peroxy ethyl ether shown in Eq. 307 takes place at the C-0 bond of the methyl ether without reduction of either the iodide or the peroxide functionalities (Eq. 307).499In contrast, a bridged peroxy ether undergoes reduction of both C-0 bonds of the peroxide linkage rather than at the ether bridge (Eq. 308) 499... 

Reduction of the keto group in naphtho derivative 115 with sodium borohydride results in 69% of the alcohol 116 (Scheme 23, Section 2.1.3.3 (1999PHA645)). Further triethylsilane reduction gives 117 in 67% yield. Synthesis of a series of pyrrolo-benzazepine and pyrrolo-benzothiazepine acetic acids (Scheme 77, Section 5.1.1 (1994MI385)) includes reduction of ketoesters 380 into corresponding hydroxyl esters, subsequent deoxygenation with iodine/PPhs and hydrolysis. 

Bennasar et al. reported a new radical-based route for the synthesis of calothrixin B (378) (869). This synthesis starts from the 2,3-disubstituted N-Boc indole 1558 and uses a regioselective intramolecular acylation of a quinoline ring as the key step for the construction of the calothrixin pentacyclic framework. Chemoselective reaction of in s/fM-generated 3-lithio-2-bromoquinoline [from 2-bromoquinoline 1559 with LDA] with the 3-formylindole 1558 followed by triethylsilane reduction of the... 

Evidence that this reduction proceeds mainly via an N-acyl iminium ion intermediate 120 was obtained by carrying out the triethylsilane reduction of 108 in deuterated trifluoroacetic acid (Scheme 49). As before, two C-4 epimeric protected kainoid analogues 121 and 122 were obtained, H NMR showing loss of the C-4 proton in both products accompanied by a simplification in the spin-spin coupling pattern of the C-5 protons.73 A close examination of the 2H NMR spectrum of each diastereoisomer did, however, reveal a trace of deuteration at C-5 indicating that a small percentage of the reduction also occurs via a benzylic carbocation intermediate 123 (Figure 12). 

A neat way of preparing96 the system (215) (useful in bufadienolide synthesis) from (214) is illustrated for compound (216). Bromination to (217) followed by dehydrobromination with lithium bromide in DMF gave the dienone (218), which on triethylsilane reduction produced (219) and thence, by condensation with diethyl oxalate, (220). Methylthiotoluene-p-sulphonate in ethanol-potassium acetate now produced (221) whose oxidation with N-chlorosuccinimide in 2% methanolic sulphuric acid gave (223). A previous route to such compounds was by way of the a-acetoxy-ketones (219) but suffers from a low yield at the acetoxylation step, (219) —> (222). 

Conversion to the Aldehyde. This transformation is accomplished through a two-step procedure. One such variant requires reduction to the alcohol (e.g. LiAllTt, H2O) and subsequent oxidation (e.g. Swem conditions). Alternatively, Wein-reb transamination " followed by Diisobutylaluminum Hydride or conversion to the thioester (see below) and subsequent Triethylsilane reduction, afford the desired aldehyde in excellent yields. Weinreb transamination proceeds with minimal endocyclic cleavage when there is a p-hydroxy moiety free for internal direction of the aluminum species. 

Dihydroxypyrrolidinones, which can be considered as cyclic GABA derivatives, are potential nootropic drug candidates. All four possible diastereomers 794—797, as shown in Scheme 174, can be prepared from tartaric acid. Treating L-tartaric acid sequentially with acetyl chloride, methyl glycinate, and then acetyl chloride provides in 81% overall yield the C2-symmetric succinimide 790. In order not to reduce the methyl ester, the very mild treatment with sodium borohydride at —40 °C is employed to prepare the cw-hydroxylactam 791 in an 80% isolated yield. Esterification of 791 with trifiuoroacetic anhydride followed by triethylsilane reduction yields to the extent of 79% the pyrrolidinone 792. This is deprotected with sodium methoxide to provide in 97% yield (3i ,45)-3,4-dihydroxy-A -methoxy-carbonylmethyl-2-pyrrolidinone (793). Ammonolysis of 793 affords (3i ,4 S)-3,4-dihydroxy-2-oxopyrrolidine-A -acetamide (794) in 60% yield. Subsequent modifications to 793 allow for the preparation of (35, 4S)-3,4-dihydroxy-2-oxopyrrolidine-A/-acetamide (795), (3R,4R)-3,4-dihydroxy-2-oxopyrrolidine-A -acetamide (796) and (35, 47 )-3,4-dihydroxy-2-oxopyrrolidine-7V-acetamide (797) [234]. 

Triethylsilane reduction of alkyl halides is even better in the presence of thiols, which act as polarity reversal catalysts for hydrogen atom transfer from silane to alkyl groups (equation 41). This reagent in the presence of AICI3 reduces even em-dichlorides to alkanes (equation 42) . The powerful hydrogen donor reagent tn s-(trimethylsilyl)silane has been introduced as a superior alternative to triethylsilane for the hydrogenolysis of... 

A route to l,5-dideoxy-l,5-imino-D-xylonolactam has utilized a 5-azido-5-deoxy-aldehydo-T>-xylose derivative,and a route to C-glycosides by reaction of aldonolactone derivatives with alkyl lithiums followed by triethylsilane reduction is elaborated in Chapter 3. 

A catalyst, usually acid, is required to promote chemoselective and regioselective reduction under mild conditions. A variety of organosilanes can be used, but triethylsilane ia the presence of trifiuoroacetic acid is the most frequendy reported. Use of this reagent enables reduction of alkenes to alkanes. Branched alkenes are reduced more readily than unbranched ones. Selective hydrogenation of branched dienes is also possible. 

Because of Us high polarity and low nucleophilicity, a trifluoroacetic acid medium is usually used for the investigation of such carbocationic processes as solvolysis, protonation of alkenes, skeletal rearrangements, and hydride shifts [22-24] It also has been used for several synthetically useful reachons, such as electrophilic aromatic substitution [25], reductions [26, 27], and oxidations [28] Trifluoroacetic acid is a good medium for the nitration of aromatic compounds Nitration of benzene or toluene with sodium nitrate in trifluoroacetic acid is almost quantitative after 4 h at room temperature [25] Under these conditions, toluene gives the usual mixture of mononitrotoluenes in an o m p ratio of 61 6 2 6 35 8 A trifluoroacetic acid medium can be used for the reduction of acids, ketones, and alcohols with sodium borohydnde [26] or triethylsilane [27] Diary Iketones are smoothly reduced by sodium borohydnde in trifluoroacetic acid to diarylmethanes (equation 13)... 

The reduction is general for a variety of substituted benzophenones Such substituents as CH3 OH, OCH3, F, Br. N(CH3)2, NO2. COOH, COOCH3, NHCOC Hreaction conditions and do not alter the course of the reduction Diarylmethanols are reduced to diarylmethanes under the same conditions and probably are the intermediates in the reduction of ketones [26] Triethylsilane also can be used as a reducing agent in trifluoroacetic acid medium [27J This reagent is used for the reduction of benzoic acid and some other carboxylic acids under mild condiUons (equation 14) Some acids (phthalic, sue cinic, and 4-nitrobenzoic) are not reduced under these conditions [27]... 

The reaction of thiyl radicals with silicon hydrides (Reaction 8) is the key step of the so-called polariiy-reversal catalysis in the radical chain reduction. The reaction is strongly endothermic and reversible with alkyl-substituted silanes (Reaction 8). For example, the rate constants fcsH arid fcgiH for the couple triethylsilane/ 1-adamantanethiol are 3.2 x 10 and 5.2xlO M s respectively. 

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. " ... 

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). 

It should be remarked here that trimethylsilane 84 a or triethylsilane 84 b and most other known silanes, for example tetramethyldisiloxane 1788, are quite expensive for any large-scale reduction, whereas the subsequently described poly-methylhydrosiloxane 1856 (cf. reductions of an azide moiety in 1855 and a carbo-benzoxy moiety in 1859) is available as large-scale orders for ca 15 kg , which is only a fraction of the cost of any other silane. 

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]. 

Combined use of Co(acac)2 and DiBAlH also gives selective reduction for a,(3-unsaturated ketones, esters, and amides.112 Another reagent combination that selectively reduces the carbon-carbon double bond is Wilkinson s catalyst and triethylsilane. The initial product is the enol silyl ether.113... 

One of the first fully characterized (monofluoromethyl)silicon compounds, CH2FSiEt3, had been obtained previously by reduction of CHFBrSiEt3 with tri-n-butyltin hydride, CHFBrSiEt3 being synthesized by insertion of CFBr into the SiH bond of triethylsilane [8]. 

Normally, only a small stoichiometric excess (2-30 mol%) of silane is necessary to obtain good preparative yields of hydrocarbon products. However, because the capture of carbocation intermediates by silanes is a bimolecular occurrence, in cases where the intermediate may rearrange or undergo other unwanted side reactions such as cationic polymerization, it is sometimes necessary to use a large excess of silane in order to force the reduction to be competitive with alternative reaction pathways. An extreme case that illustrates this is the need for eight equivalents of triethylsilane in the reduction of benzyl alcohol to produce only a 40% yield of toluene the mass of the remainder of the starting alcohol is found to be consumed in the formation of oligomers by bimolecular Friedel-Crafts-type side reactions that compete with the capture of the carbocations by the silane.129... 

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