Tris silane esters

Reduction by hydrogen atom donors involves free radical intermediates and usually proceeds by chain mechanisms. Tri-n-butylstannane is the most prominent example of this type of reducing agent. Other synthetically useful hydrogen atom donors include hypophosphorous acid, dialkyl phosphites, and tris-(trimethylsilyl)silane. The processes that have found most synthetic application are reductive replacement of halogen and various types of thiono esters. 

Scheme 5.9 illustrates some of the conditions that have been developed for the reductive deoxygenation of alcohols. Entries 1 to 4 illustrate the most commonly used methods for generation of thiono esters and their reduction by tri-M-butylstannane. These include formation of thiono carbonates (Entry 1), xanthates (Entry 2), and thiono imidazolides (Entries 3 and 4). Entry 5 is an example of use of dimethyl phosphite as the hydrogen donor. Entry 6 uses r .s-(trimethylsilyl)silane as the hydrogen atom donor. 

The ruthenium carbene catalysts 1 developed by Grubbs are distinguished by an exceptional tolerance towards polar functional groups [3]. Although generalizations are difficult and further experimental data are necessary in order to obtain a fully comprehensive picture, some trends may be deduced from the literature reports. Thus, many examples indicate that ethers, silyl ethers, acetals, esters, amides, carbamates, sulfonamides, silanes and various heterocyclic entities do not disturb. Moreover, ketones and even aldehyde functions are compatible, in contrast to reactions catalyzed by the molybdenum alkylidene complex 24 which is known to react with these groups under certain conditions [26]. Even unprotected alcohols and free carboxylic acids seem to be tolerated by 1. It should also be emphasized that the sensitivity of 1 toward the substitution pattern of alkenes outlined above usually leaves pre-existing di-, tri- and tetrasubstituted double bonds in the substrates unaffected. A nice example that illustrates many of these features is the clean dimerization of FK-506 45 to compound 46 reported by Schreiber et al. (Scheme 12) [27]. 

The radical source must have some functional group X that can be abstracted by trialkylstannyl radicals. In addition to halides, both thiono esters and selenides are reactive. Allyl tris(trimethylsilyl)silane can also react similarly.232 Scheme 10.11 illustrates allylation by reaction of radical intermediates with allylstannanes. 

Acid catalysis—hydrolysis. Several series of alkylsilane esters were studied to determine the effect of silane structure on the hydronium ion catalyzed hydrolysis reaction. The hydronium ion catalyzed hydrolysis rate constants for a series of alkyl tris-(2-methoxyethoxy)silanes in aqueous solution were used to define the modified Taft equation log(A /Ah ) = 0.39a + 1.06ES, where Ho is the rate of hydrolysis for methyl tris-2-(methoxyethoxy)silane [42], The hydronium ion catalyzed hydrolysis rate constants and the reaction half-lives are reported in Table 2. In a similar manner, the hydronium ion catalyzed hydrolysis rate constants for a series of trialkylalkoxysilanes in 55% aqueous acetone were used to obtain the modified Taft equation log(/cH//cHo) = -0.37 a + 2.48 E where kHo is the rate of hydrolysis for trimethylalkoxy-silane. 

Tris(trimethylsilyl)silane is found to be an efficient reducing agent for a variety of functional groups. In particular, the reduction of halides, chalcogen groups, thiono esters and isocyanides are the most common ones. The efficiency of these reactions is also supported by available kinetic data. The rate constants for the reaction of (TMS)3Si radicals with a variety of organic substrates are collected in Table 2. 

High molecular weight perfluorinated tertiary alcohols can be prepared by the reaction of (perfluoroalkyl)- and (perfluorooxaalkyl)trimethylsilanes with fluoro ketones (vide supra). The reaction has been extended to carbonyl compounds other than ketones acid fluorides gave ketones, but no reaction was observed with esters. a-Oxo esters react with trimethyl(tri-fluoromcthyl)silane with fluoride initiation in tetrahydrofuran /(./(. -trifluoro lactic acid derivatives are produced in good yields in one step. 

Activated esters, such as oxalates, are also reactive towards trimethyl(perfluoroalkyl)silanes under fluoride catalysis as reported in the case of di-/cr/-butyl oxalate which affords tri-fluoropyruvic acid 26 (Rp = CFj) in hydrated fonn. ""... 

Asymmetric induction is used in the stereoselective synthesis of silanes via the hvdrosilyla-tion of a,/l-unsaturated esters30. The addition of the tris(trimethylsilyl)silyl radical to the double bond is highly regioselective. yielding an ester-substituted radical that abstracts hydrogen diastereoselectively. 

Similar conditions have been applied to 2-methy -3-oxoamides, except that tris(diethyl-amino)sulfonium difluorotrimethylsilicate (TASF) was used as the fluoride source and 1,3-dimethyl-3,4,5.6-tetrahydro-2(l//)-pyrimidinone (DMPU) as solvent3,4. Again the results were generally complementary to those given by the silane/trifluoroacetic acid system, in that the ewfi-product w as formed predominantly. However, the method only worked reliably for amides where R1 is aryl. The ester (5)-methyl 2-benzoylpropanoate failed to react, possibly because of deprotonation by fluoride4. 

Triphenylsilyl ethers are typically prepared by the reaction of the alcohol with triphenylsilyl chloride (mp 92-94 °C) and imidazole in DMF at room temperature. The dehydrogenative silylation of alcohols can be accomplished with as little as 2 mol% of the commercial Lewis acid tris(pentaf1uorophenyl)borane and a silane such as triphenylsilane or triethylsilane [Scheme 4.98]. Primary, secondary, tertiary and phenolic hydroxyls participate whereas alkenes, alkynes, alkyl halides, nitro compounds, methyl and benzyl ethers, esters and lactones are inert under the conditions. The stability of ether functions depends on the substrate. Thus, tetrahydrofurans appear to be inert whereas epoxides undergo ring cleavage. 1,2- and 1,3-Diols can also be converted to their silylene counterparts as illustrated by the conversion 983 98.4. Hindered silanes such as tri-... 

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