Addition of Sulfur Nucleophiles

The access toward tetrahydrothiophenes via domino thia-Michael/aldol reactions has been well studied recently [29]. Jorgensen et al. [29d] introduced an organocat-alytic approach toward optically active and highly substituted tetrahydrothiophenes by the treatment of a,fi-unsaturated aldehydes with 2-mercapto ketones. The corresponding products were obtained as single diastereomers in moderate yields and very good enantioselectivities (Table 8.8). Depending on the additive, they 

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Table I. Pseudo first-order rate constants for Michael addition of sulfur Nucleophiles (5 mM) to aciylic acid and acrylonitrile in seawater medium (salinity 35 and reaction pH 8.3 0.2)...

Carbon-Sulfenyl Sulfur Bond Formation 5.1.1. Addition of Sulfur Nucleophiles to Unsaturated Compounds 5.1.1.1. Addition of Thiols or Thioacids... 

The addition of sulfur nucleophiles to aldehydes and ketones may be exemplified by the formation of hydrogensulfite (bisulfite) adducts (3.12). These are sulfonates that are water soluble. However, their stcric bulk means that whereas they are formed from aldehydes and methyl ketones, more highly substituted ketones are reluctant to form these derivatives. 

Addition of sulfur nucleophiles such as phenylthiolate to diethyl l-(ethoxycarbonyl)vinylphos-phonate has been used in the synthesis of P-acetoxy- and p-hydroxy-a-methylene-y-butyrolac-tones Similarly, addition of isopropylthiolate to diethyl l-(ethoxycarbonyl)vinylphosphonate represents a key step in the synthesis of a-methylidenebutyrolactones such as confertin (Scheme arteannuin B, - - rhopaloic acid and hippospongic acid A Addition... 

Nucleophilic addition of sulfur nucleophiles formation of thioacetals... 

The addition of sulfur nucleophiles to alkynes is a less developed transformation. However, Yamamoto described the attack of the sulfur atom of aryl thioethers to afford benzothiophenes (equation 31). More recently, it has been showed that propargylic thioethers or thioacetals undergo migration to give carbenes that cyclize in hydroarylation processes and thiocarbamates that evolve by propargylic rearrangement. Thiosilanes can perform as both sulfur nucleophiles and silicon electrophiles in intramolecular reactions to afford benzothiophenes (equation 32). ... 

For a recent review covering the catalytic asymmetric conjugate addition of sulfur nucleophiles see D. Enders, K. Liitgen and A. A. Narine, Synthesis, 2007, 959. 

The addition of sulfur nucleophiles to (x,P-unsaturated sulfoxides is known, although the stereochemical outcome of such additions has not been studied extensively [12,72,94],... 

Conjugated dienes and activated olefins like indene undergo intermolecular gold-catalyzed additions of sulfur nucleophiles. Aliphatic and aromatic thiols, as well as thioacids, afforded the hydrothiolation products with good yield in the... 

In 2005, J0rgensen et al. extended the conjugate addition of sulfur nucleophiles to a,P-unsaturated aldehydes under iminium catalysis with trimethylsilyl ether 56 (10 mol%) as catalyst [385]. Very high enantioselectivities (89-97% ee) were reported for the addition of aliphatic thiols to different aromatic and aliphatic enals at low temperatures (-24°C) where the employment of an acid cocatalyst (PhCOjH, 10 mol%) was mandatory in order to improve the reaction rate. This methodology has been incorporated into domino reactions by the same group and others to successfully prepare optically active sulfur-containing heterocyclic compounds [385, 386],... 

Recently an expansion of the electrophile scope of the conjugate addition of sulfur nucleophiles has been reported by different groups. As depicted in Fig. 2.29 for selected examples, Cinchona-denwed catalysts 203 and 205 promote highly enantioselective additions to nitrooleflns [387] and a,p-unsaturated V-acylated oxazolidin-2-ones [388] through non-covalent catalysis. Especially interesting results the Michael reaction to P-substituted nitroacrylates catalyzed by chiral thio-... 

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%). 

The organocatalyzed conjugate addition of sulfur nucleophiles to electron-poor alkenes is probably the most frequently used process for the asymmetric formation of C—S bond [2b, 5]. Analogously, the employment of selenium nucleophiles may, in principle, be used for the formation of C—Se bonds. Because previous reviews were already reported on this topic, more recent reports are especially highlighted in this chapter. 

Addition of Sulfur Nucleophiles to C-C Multiple Bonds 457 NHCbz (11.49)... 

The addition of sulfur nucleophiles to activated alkenes is a popular and valuable approach to the synthesis of sulfur-carbon(sp ) bonds. Due to the importance of the products, a vast array of catalysts and conditions have been developed to promote this reaction. One of the most direct approaches to these thia-Michael additions entailed simply stirring a thiol with the activated alkene in water (Scheme 5.4) [4]. This remarkably straightforward approach was also fast, and outstanding yields of a range of sulfides were obtained in less than 15 min. It should be noted that water was critical for the success of this reaction. Removing the water and performing the reaction under neat conditions was less successful. 

Table 2.17 Hetero Michael addition of sulfur nucleophiles...

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