Sulfides, alkenyl coupling reactions

Allyiic halides, alcohols, ethers, acetates, lactones, phosphates, epoxides, sulfides, sulfonium salts, se-lenides and ammonium salts undergo transition metal catalyzed coupling reactions with C(sp )—Li, —Mg, —B, —Al, —Sn, —Zt, —Cd and — Hg reagents. Table 1 summarizes the allyiic leaving groups, alkenyl and aryl metallic reagents, catalytically active metals and references and Table 2 the regio- and stereo-chemical aspects. 

Pyrimidines stannylated in the 4-position are active in coupling reactions. 5-Chloro-4-stannylpyrimidines, either as 2-sulfide or 2-one, are coupled with alkenyl or aryl halides to form 208, 210, and 212. With an acid chloride, ketone 213 is formed in the absence of catalyst, which has an otherwise deleterious effect on the reaction. The reaction between thiophene-2-carbonyl chloride and the 4-stannylpyrimidine is run at -78°C (94T275). 

Scheme 5.11 Ni-catalyzed cross-coupling reaction of a7lmagnesium reagents with a l and alkenyl sulfides [51, 52].

Hoshino, Y Ishiyama, T. Miyaura, N. Suzuki, A. 1988. A stereoselective route to alkenyl sulfides through the palladium-catalyzed cross-coupling reaction of 9-Alkyl-9-BBN with 1-Bromo-l-phenylthioethene or (E)- and (Z)-2-Bromo-l-phenylthioalkenes. Tetrahedron Lett. 29 3983-3986. 

This method has been exploited in a synthetic sequence leading to salvinorin A that shows potent K opioid agonist activity. Alkenyl sulfrdes can also be employed as electrophiles in iron-catalyzed cross-coupling reactions with Grignard reagents (Scheme 4-215). The reaction is chemoselective for alkenyl sulfides, whereas aryl sulfides show only very low reactivity. ... 

Aryl and alkenyl phenyl sulfides are prepared by the reaction of aryl and alkenyl halides and inflates with tributylstannyl phenyl sulfide. 2-Chloropyrimidine (737) is used for the coupling[606,607]. The diaryl or divinyl sulfide 739 is prepared by the reaction of distannyl sulfide (738)[548], N,N-Diethylaminotributyltin (740) reacts with aryl halides to give arylamines[608]. 

The iron-catalyzed cross-coupling between Grignard reagents and alkenyl sulfides was also studied (Scheme 26) . Unfortunately, this reaction is very sensitive to steric and electronic effects and only two products were synthesized in modest yields. In fact, the scope of the reaction is very limited since only vinyl sulfides can be used. 

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. ... 

Ma recently demonstrated that 2-haloanilides can undergo coupling with metal sulfides subsequent intramolecular condensation affords substituted benzothia-zoles (3). Thioamides and thioureas also serve as precursors to benzothiazoles (vide infra). In addition to S -arylation reactions, alkenyl halides are also effective... 

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. 

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