Sulfur nucleophiles, reaction with aryl halides

Other sulfur nucleophiles can be used in the metal-catalyzed C—S bond-forming chemistry. Takagi, Iwachido, and Hayama reported the reaction of aryl halides with thioamide nucleophiles to produce 2-alkylbenzothiazoles, as shown in Eq. 10. ° The presence of CaO base increased the yield significantly, and the use of phosphorus ligands increased the turnover numbers of the catalysts. This chenustry tolerated 2-CH3, 2-CH2OCH3, 2-CH2CN, 4-Br, 5-Cl, 5-CH3, and 5-CF3 substitution of the iodo aniline, bnt not 2-aryl substitution. 

This section describes selected arylations of phosphorus, sulfur, and halide nucleophiles under metal-free and metal-catalyzed conditions. Arylations of other nucleophiles, e.g., selenium and tellurium, have been reviewed previously [4]. Aryl phosphonates [ArPO(OR)2] can be synthesized by arylation of phosphite anions with diaryliodonium salts and NaH in DMF at 70-80 °C [158]. A copper-catalyzed arylation of various phosphorous nucleophiles, e.g., diarylphosphine oxides and //-phosphonates, was recently reported to proceed at room temperature. The observed chemoselectivity with unsymmetric salts was opposite to the general trend in metal-catalyzed reactions (see Sect. 2.1), which was explained by a radical mechanism [159]. 

In summary, sulfonamides are most commonly prepared by the reaction of amines with sulfonyl halides. Aryl sulfonyl chlorides may be accessed from C-H bonds by chlorosulfonylation, from C-S bonds by oxidation, from C-N bonds by diazotization, or from C-X bonds by metalation. Approaches to all l sulfonamides are more limited as they are typically prepared by either oxidative chlorination of thiols or addition of organometallic nucleophiles to sulfur electrophiles. Traditional sulfonamide preparation has frequently necessitated harsh reagents and conditions, but the development of Pd-catalysed approaches and discovery of new sulfur dioxide sources allow for operationally simple sulfonamide synthesis under mild conditions. Future directions in sulfonamide synthesis will likely involve the direct C-H installation of sulfonamides without the use of hazardous reagents. 

The synthetic utility of many of the substitution reactions described so far is limited because there are well-established thermal routes to the same products. However, a third group of photochemical nucleophilic substitutions involves aryl halides and nucleophiles based on sulfur, phosphorus or, of particular importance, carbon. Two examples are the reaction of bromobenzene with the anion of t-butyl methyl ketone 13.12), and the replacement of bromine by cyanomethyl in 2-bromopyridine (3.13). This type of reaction offers a clear advantage over lengthy thermal alternatives, and intramolecular versions have been used in the synthesis of indoles (e.g. 3.14) or benzofurans from o-iodoaniline or o-iodoanisole respectively. 

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