Substrate-directed Heck-Matsuda reaction

SUBSTRATE-DIRECTED HECK-MATSUDA REACTION 2.1 Some Preliminary Results... 

DEVELOPMENT AND SYNTHETIC APPLICATIONS OF THE SUBSTRATE-DIRECTED HECK-MATSUDA REACTION... 

TABLE 4 Substrate-Directed Heck-Matsuda Reaction with Allylamine Derivatives... 

SCHEME 28 Substrate-directed Heck-Matsuda reaction of olefins 112 and 113. 

In summary, the substrate-directed Heck-Matsuda reaction was successfully applied for the synthesis of polyfunctionalized cyclopentenes under very mild conditions. The method is very robust, and aryldiazonium salts with distinct electronic or steric properties were well tolerated. The power of this methodology was demonstrated by the total synthesis of the VPC01091 (130), an agonist of the SlPi receptor, a potential new drug for the treatment of multiple sclerosis. ... 

In this review, we described the development of the substrate-directed Heck-Matsuda reaction from its detection as an unplanned result, which stimulated our imagination and curiosity, leading to its realization as a valuable tool in organic synthesis. 

This methodology was also applied to the stereoselective arylation of substituted cyclic compounds to provide highly complex aryl-substituted cyclo-pentene scaffolds with total control of the double bond position. This unique substrate-directed Heck-Matsuda reaction was applied in the total synthesis of the SlPi agonist VPC01091 (130). 

As the substrate-directed Heck-Matsuda reactimi promoted a significant increase in structural complexity, we envisioned that VPC01091 (131) could be synthesized in a straightforward manner starting from the Heck adducts of the reaction between 112 and the corresponding aryldiazonium salt (Scheme 31). 

These substrate-directed Heck reactions allowed the synthesis of pharmacologically active compounds in a very straightforward way. For example, compotmd 26 was oxidized with DDQ to provide the natural product yango-nine 27. Additionally, methysticin 28 was obtained in 59% yield (95% based on recovered starting material) directly from the Heck-Matsuda reaction. The chemoselective reduction of the least hindered double bond of 28, using Pd/C as catalyst, provided dehydromethysticine 29 in 95% yield (Scheme 11). 

---