Vinylic imines, palladium-catalyzed coupling

Application of carbon-carbon cross-coupling/67C-electrocyclization cascade reactions in pyridine synthesis is well known. Larock and coworkers developed a palladium-catalyzed coupling of vinylic imines 279 with terminal alkynes 280 followed by subsequent copper-catalyzed cyclization of 281 to give aryl, vinyl, and alkyl-substituted pyridines 282 in moderate yields. ... 

In 2003, when the second edition appeared, it was clear that the Stille chemistr/ had really come of age, as shown by the increasing number of applications of palladium-catalyzed cross-coupling reactions of vinyl- and arylstannanes in natural product synthesis and in advanced organic synthesis. In the past decade, these types of applications, of course, remained very important and, in addition, the use of allylstannanes in palladium-catalyzed coupling reactions received much attention. Cross-coupling of allylstannanes with imines also forwarded the area of asymmetric catalysis. 

Larock and Dai developed the synthesis of isoquinolines via palladium-catalyzed coupling of organic halides with 2-(l-allqmyl)benzaldimines. Starting from N-tert-butyl-2-(l-alkynyl)benzaldimines and aiyl, allylic, benzylic, alkynyl halides, as well as a vinylic halide, the corresponding 3,4-disubstituted isoquinolines with aryl, allylic, benzylic, 1-alkynyl, and vinylic substituents, respectively, in the 4-position were produced in good yields. The reaetion appears to require an aiyl group on the end of the acetylene furthest from the imine functionality. 

Lithiation of compound 560 with s-BuLi-TMEDA in THF at —78 °C following an inverse addition protocol provided the anion 561. It reacts with primary alkyl iodides and triflates, silyl chlorides, diphenyl disulfide, epoxides, aldehydes, ketones, imines, acyl chlorides, isocyanates and sulfonyl fluorides to yield the expected compounds 562 (Scheme 152). The transmetallation of compound 561 with ZnBr2 allowed the palladium-catalyzed cross-coupling reaction with aryl and vinyl bromides837. When the reaction was quenched with 1,2-dibromotetrafluoroethane, the corresponding bromide 562 (X = Br) is obtained838. 

The installation of the pharmacologically important isoquinoline group was achieved by a Stille coupling. Reduction by diimide yielded the trans-fused perhydroindane subunit in 329. An oxidation, enol triflation and reduction sequence converted 329 to enone 331. Enol triflation and deprotection afforded 332. Palladium-catalyzed vinylation, followed by a Parikh-Doering oxidation gave 333. The final and rather splendid step consisted of dimethyl imine-formation and vinysilane cyclization to furnish cortistatin J in high yield and with the correct dimethylamine stereochemistry (Scheme 18.66). 

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