Reductive coupling triethylsilane

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 synthesis of the right-hand fragment of ziprasidone started with a Wolff-Kishner reduction of isatin 43 to give the oxmdole 44 (Scheme 14). Friedel-Crafts acylation with chloroacetyl chloride afforded aryl ketone 45, which was reduced with triethylsilane in trifluoroacetic acid to the phenethyl chloride 46. The two fragments were joined by alkylation of 40 with 46 in the presence of Nal and Na2CO3 to give ziprasidone (4) in low yield. The yield of the coupling step was improved dramatically when the reaction was conducted in water (Scheme 15). 

A palladium-catalysed reduction of ethyl thiolesters to aldehydes with triethylsilane has been proposed by Fukuyama [2611. The reaction, coupled with a mild conversion of carboxylic acids to thiolesters (see [261], footnote 2), affords a versatile method for the overall transformation of... 

McMurray [151] has described the acid-assisted cleavage of the N]-C4 bond in trans 4-hydroxyphenyl p-lactams. The ring opening reaction may proceed with concomitant reduction or formation of carbon-carbon coupling products, as a function of the reagent employed. For instance, Scheme 60, treatment of 196 with 4 equivalents of triethylsilane in neat trifluoroacetic acid led to compound 197. On the contrary, treatment with anisole in trifluoroacetic acid led to compound 198. Unfortunately, no data are provided by authors regarding process yield or final diastereomeric ratio. 

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). 

The mechanism for this palladium-catalyzed cross-coupling reaction comprises the initial oxidative addition of the electrophile 37 to the palladium(O) catalyst followed by transmetallation of triethylsilane to yield the corresponding bis(organo)palladium(II) complex 39, which then undergoes reductive elimination to form the alkene 40 and to regenerate the palladium(O) catalyst. 

SCHEME 5.63 Ni(COD)-IMes-catalyzed reductive coupling of alkynes, aldehydes, and triethylsilanes. 

Keywords Ynoates, aldehydes, triethylsilane, Ni(COD>2, SIPr.HBF4, KO Bu, PPh3, THF, room temperature, regioselective reductive coupling, multicomponent reaction (MCR), silyl-protected Y-hydroxy-a,p-enoates... 

Similar to the results discussed for the silylcarbocyclizations of carbon-carbon multiple bonds, reductive cyclizations in the presence of carbonyl compounds are readily achieved. Crowe has developed a titanium-catalyzed procedure for the intramolecular reductive coupling of i5, -unsaturated carbonyl compounds in the presence of triethoxysilane (eq 18).The electronic advantage of triethoxysilane is demonstrated by the lack of reductive coupling in the presence of less reactive silanes, such as triethylsilane and diphenylsilane. With this method, Mori has utilized nickel(O) catalysts to generate five- and six-membered carbocycles and pyrrolidine derivatives. Furthermore, coordination of a chiral phosphine ligand to the nickel catalyst renders the reaction moderately enantioselective. ... 

The reductive couplings of aldehydes with unsymmetrical internal alkynes are catalyzed by Ni(COD)2 and an imidazolidene ligand in the presence of 2 equivalents of triethylsilane to give regioselectively the corresponding allyl silyl ethers [189]. 

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