Thiol catalysts

Arthur L. Weber (1998), now working at the Seti Institute of the Ames Research Center at Moffett Field, reports the successful synthesis of amino acid thioesters from formose substrates (formaldehyde and glycolaldehyde) and ammonia synthesis of alanine and homoserine was possible when thiol catalysts were added to the reaction mixture. On the basis of his experimental results, Weber (1998) suggests the process shown in Fig. 7.10 to be a general prebiotic route to amino acid thioesters. 

Radical-chain cyclization of alkenyloxysilanes using thiol catalysts give five-membered ring products (via a 5-endo cyclization) in the case of allyloxysilanes... 

Scheme 19)." Homoallyloxysilanes gave a mixture of five- and six-membered rings, but the intermediate silyl radical underwent predominantly 6-endo cyclization. Pentenyloxysilane gave the 1-endo product only. The stereochemistry of these reactions was found to be determined by steric effects, even in the presence of chiral thiol catalysts. The structures of the radical intermediates were studied by EPR. 

The addition of silanes across alkenes has been investigated both experimentally145 and theoretically.146 The effect of optically active thiol catalysts to catalyse radical hydrosilylation (polarity reversal catalysis) has been studied. The use of 2,3,4,6-tetra-O-acetyl-thio-jS-D-glucopyranose as the chiral thiol (used to reduce the intermediate carbon-based radicals) furnished the hydrosilylated alkenes in low to moderate enantiomeric excesses.145 In addition to this work a theoretical study on the reactions of SiH3 with ethene and propene has been undertaken using PMP2(6-31G ) and QCISD(T)(6-31G ) methods. Results indicated that the alkene-addition pathway is favoured over the alternative possible mode of reaction (H-abstraction). This is contrary to that previously suggested for the reaction of SiF with propene.146... 

The efficiency of this approach was first studied through the radical reduction of 1-bromoadamantane by Et3SiH in presence of the polyHIPE-supported thiol catalyst (table l).The conversion of 1-bromoadamantane is complete after 1 hour at 80°C with a catalytic amount of dodecanethiol and two equivalents of triethylsilane. In the same conditions, 70% of the bromide were reduced in the presence of the supported thiol, showing a lower reactivity of this last one. The absence of reduction without thiol proved the role of the supported thiol. 

Alkyne Thiol Catalyst Temperature ( C) Product Yield (%) Ref. 

Reasonable levels of enantioselectivity are also observed for the chiral hydro-silation of alkenes using optically active thiol catalysts. Several catalysts were screened, and it was found that the sugar-derived catalyst 89 provided optimal levels of selectivity at a loading of only 5 mol% (Eq. 24). 

The stereoselective Rauhut-Currier reaction catalysed by a cysteine derivative has been explored computationally with DFT (M06-2X). Both methanethiol and a chiral cysteine derivative have been studied as nucleophiles. The complete reaction pathway involves rate-determining elimination of the thiol catalyst from the Michael addition product and the stereochemistry has been found experimentally to be extremely sensitive to the reaction conditions, such as the number of water equivalents and the effect of potassium counterion. 

Athene Hydrogenations. Treatment of olefins with Zr catalysts effected their saturation in 50% yield along with 50% dehydrogenative silylation as calculated by GC (eq 20). Ru car-bene complexes also afforded the reduced product in the presence of PhsSiH. Reduction of an olefin via radical-chain reductive car-boxyalkylation proceeded with PhsSiH and a homochiral thiol catalyst upon TBHN initiation (eq 21). The olefin of vinylstan-nanes could be reduced without any protodestannylated product produced (eq 22). ... 

More recently. Miller and coworkers reported that ortho-mercaptobenzoic acid and ortho-mercaptophenols 159 could be used as efficient thiol catalysts in both the intramolecular MBH and Rauhut-Currier reaction and they also demonstrated that chiral mercaptophenol afforded the reaction with low to moderate enantiose-lectivities (Scheme 31.53) [64]. Under estabhshed conditions, chiral catalysts (S)-and (R)-160 afforded high yields and moderate asymmetric inductions in the MBH reactions. The obtained enantioselectivities remained largely unaffected by the amount of water and base added, catalyst loading, and substrate concentration but were markedly influenced by the reaction temperature. Interestingly, both increasing and decreasing the temperature from the established value of 70 °C resulted in lower ee values. The complete absence of catalytic activity of (R)-161 further emphasizes the crucial importance of a protic substituent at the ortho-position to the nucleophilic thiol. 

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