Sulfide derivatives cross-coupling

The thioboration of terminal alkynes with 9-(alkylthio)-9-borabicyclo[3.3.1]-nonanes (9-RS-9-BBN) proceeds regio- and stereoselectively by catalysis of Pd(Ph,P)4 to produce the 9-[(Z)-2-(alkylthio)-l-alkeny)]-9-BBN derivative 667 in high yields. The protonation of the product 667 with MeOH affords the Markownikov adduct 668 of thiol to 1-alkyne. One-pot synthesis of alkenyl sulfide derivatives 669 via the Pd-catalyzed thioboration-cross-coupling sequence is also possible. Another preparative method for alkenyl sulfides is the Pd-catalyzed cross-coupling of 9-alkyl-9-BBN with l-bromo-l-phe-nylthioethene or 2-bromo-l-phenylthio-l-alkene[534]. 

Another very important aspect of these transition metal-catalysed cross-coupling reactions stems from the high selectivity observed with stereo-defined vinyl sulfides. Applications to the stereoselective syntheses of pheromones were straightforward (see [321] and references therein), as shown in the two-step synthesis of muscalure from (Z)-l-bromo-2-phenylthioethylene [322] involving its sequential coupling through the bromo and phenylthio substituents with the appropriate derivatives. 

On the other hand, sodium methoxyalkenyldialkylborates derived from 9-BBN or dicyclohexylborane, undergo stereospecific cross-coupling at —15 °C with allylic halides in the pr ent of cuprous bromide-methyl sulfide to yield stereodefined 1,4-alkadienes (Eq, 94)... 

Alkenes. Titanocene bis(triethyl phosphite), which is prepared in situ from titanocene dichloride, triethylphosphite, and Mg, promotes carbonyl olefmation with gem-dichlorides and dithioacetals [e.g., l,l-bis(phenylthio)cyclobutane ] including those derived from enals (to give 1,3-dienes). Enol ethers-and alkenyl sulfides are obtained in the analogous reaction with dithioorthoformates and trithioorthoformates. Cross-coupling of dithioacetal and thiolesters furnishes predominantly (Z)-alkenyl sulfides. ... 

The general reaction mechanism has been shown to involve typical steps for cross-coupling [98, 113]. Oxidative addition of an aryl halide generates a Pd(II) species that undergoes transmetalation to form a Pd(II)-thiolate. C-S reductive elimination provides the aryl sulfide and regenerates the Pd(0) catalyst. More recently, Hartwig reported a detailed mechanistic analysis of the Pd/Josiphos system derived from different Pd precursors. The dominant Pd species were found to be off the catalytic cycle, which accounted for differences in rates between stoichiometric and catalytic reactions [114]. Thioketones are also effective thiolate nucleophiles for C-S bond formation. The reaction involves tandem Pd-catalyzed thioenolate alkylation, followed by 5-arylation (8) [102]. Presumably, the arylation process proceeds by a similar mechanism to related Pd-catalyzed transformations. 

Cross-coupling of the silyl derivatives of thiols R3SiSH led to the formation of vinyl (or aryl) silylsubstituted sulfides (Scheme 3.4) [10]. Further transformation of the products in alkylation or Pd-catalyzed alkenylation reactions was reported as a route to unsymmetric RSR sulfides as final products. This stepwise synthetic approach allowed avoidance of the use of some scarcely available Ar(Het)SH, which otherwise would be required to prepare the same final products in a single step utilizing crosscoupling. 

The sahent work of Wenkert and Julia [41, 69, 78] on aryl sulfide, sulfoxide, and sulfone derivative - Grignard cross-coupling may be advanced to S-arylcarbamates (Table 14.11, entries 10-12) for which more vigorous conditions than those... 

Dilithium tetrachlorocuprate is recommended as an additive for cross coupling of Grignard compounds with tosylates even allylic and benzylic acetates give good yields . a-Methylene-ketones, -carboxylic acids and -lactones have been prepared via sulfides and sulfoxides. A convenient and general synthesis of acetylene derivatives from boranes via the reaction of iodine with lithium 1-alkynyltriorganoborates has been published ar-Nitrostyrenes can be easily obtained by a Wittig synthesis with formaldehyde in an aqueous medium . A new synthesis of unsym. ketones by reaction of dialkyldiloroboranes with lithium aldimines has recently been published . Metallo aldimines have also served for the synthesis of a variety of other compound classes such as a-hydroxyketones, a-keto acids, nitriles, and for the asym. synthesis of a-amino acids . Polycondensations of malononitriles with benzylic chlorides have been carried out quantitatively under mild conditions in dimethyl sulfoxide with triethylamine as acid acceptor . Carbonyl compounds can react with dibromoacetonitrile to yield a-bromo esters with additional carbon atom . ... 

Palladium-catalyzed Cross-coupling Reactions. The Pd -catalyzed cross-coupling of vinyl and aryl halides with KSTIPS affords the corresponding silyl sulfides, which can be used either to prepare thiols or sulfides. The reaction proceeds with corr5>lete retention of configuration in the case of vinyl derivatives (eq 8). The yields are good to excellent (61-93%) when the reaction is earned out on a small scale (2 mmol). 

Arenethiols are important intermediates in chemical synthesis. While there are numerous reactions to introduce this functionality starting from aryl halides or phenols, most of these transformations require drastic reaction conditions and tolerate few if any functionalities. Despite the fact that in the last few years the efficiency of palladium-catalyzed cross-coupling reactions for the preparation of aryl ethers and aniline derivatives has improved greatly (see 5.1 and 5.2), analogous methods for the formation of aryl sulfides and especially arenethiols have lagged behind. The first report of a mild palladium-catalyzed synthesis of arenethiols came from Rane et followed by reports from a Zeneca Pharma group and a Merck group (Scheme 5-160). ... 

Ishiyama T, Nishijima K, Miyaura N, Suzuki A. Palladium (O)-catalyzed thioboration of terminal alkynes with 9-(alkylthio)-9-borabicyclo[3.3.1]nonane derivatives stereoselective synthesis of vinyl sulfides via the thioboration-cross-coupling sequence. J. Am. Chem. Soc. 1993 115 7219-7225. 

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