Addition of Thiols and Thiocarboxylic Acids

The preferred stereochemistry of addition to cyclic alkenes is anti The additions are not as highly stereoselective as hydrogen bromide addition, however. 

Both substitution and addition reactions can occur intramolecularly. Intramolecular substitution reactions that involve hydrogen abstraction have some important synthetic applications, since they permit functionalization of carbon atoms relatively remote from the initial reaction site. The preference for a six-membered cyclic transition state in the hydrogen abstraction step imparts considerable position selectivity to the process. 

There are several reaction sequences which involve such intramolecular hydrogen abstraction steps. One example is the photolytically initiated decomposition of N-haloamines in acidic solution, which is known as the Hofmann-Loeffler reac- 

There are related procedures involving iV-haloamides which lead to lactones via iminolactone intermediates.  

A procedure for intramolecular functionalization of alcohols has been developed in studies carried out primarily with steroid derivatives. The alcohol is converted to a nitrite ester by reaction with nitrosyl chloride. Photolysis effects 

The addition of S-H compounds to alkenes by a radical chain mechanism is a quite general and efficient reaction.The mechanism is analogous to that for hydrogen bromide addition. The energetics of both the hydrogen abstraction and addition steps are favorable. The reaction exhibits anti-Markovnikov regioselectivity. 

The preferred stereochemistry of addition to cyclic alkenes is but the additions 

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By addition of thiols to isonitriles thioformimidates (274 equation 147) are accessible. 2-Methyl-propaneisonitrile inserts into the thietane system to give triiminothiolanes (275 Scheme 42). A related insertion of isonitriles into a C—S bond was observed in the reaction of alkylmercaptocyanoacetic acid esters, labile thioimidates (276) are the products. - The addition of thiocarboxylic acids to isonitriles, giving mixed anhydrides of thioformimidic acids and carboxylic acids has been studied. ... 

In this method, the cyclic peptide is generated through cysteine-perthioester cyclization to afford a Xaa-Cys bond whose thiol is then used for the second ligation step to the core through a thiol addition reaction (Scheme 25).[S71 For the perthioester cyclization, the linear precursor 91 consists of an activated N-terminal Cys(Npys) and a C-terminal thiocarboxylic acid which favors cyclization due to intramolecular mixed disulfide formation between them. 

Few examples have been reported for the organocatalytic asymmetric conjugate addition of sulfur nucleophiles other than thiols. The reaction of thiocarboxylic acids to cyclohex-2-enones [390] and a,p-nnsatnrated esters [391] was initially studied by Wynberg et al. employing Cinchona alkaloid catalysts with limited success in terms of selectivity (up to 54% ee). Slightly better enantioselectivities have been recently obtained by Wang et al. in the 1,4-addition of thioacetic acid to P-nitrostyrenes (up to 78% ee) [392] and trani-chalcones (up to 65% ee) [393], using Takemoto s thiourea 142 as catalyst (2-10 mol%). 

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