Unexpected high regiocontrol in Heck reaction of fluorine-containing electron-deficient olefins—Highly regio- and stereoselective synthesis of β-fluoroalkyl-α-aryl-α,β-unsaturated ketones

Evolution and Synthetic Applications of the Heck–Matsuda Reaction: The Return of Arenediazonium Salts to Prominence

“…In a subsequent study, other electron-withdrawing groups in the place of the ketone including esters, sulfones, phosphonate esters, and a nitro group were found to influence the efficacy of the reaction and provided very low yields of the products. [66] Besides the fact that yields were moderate for the unsaturated ketones, the most peculiar aspect of these results was the predominant formation of α-arylated Heck adducts 22 and 23 in preference to the expected β-arylated unsaturated ketone. Optimization studies also revealed that the presence of a phosphane ligand was strikingly beneficial for improving yields, which is contrary to the current understanding of the HM reaction.…”

“…[86] Another example of a stereoselective total synthesis using an arylated oxygen heterocycle derived from a HM reaction is observed in the synthesis of (-)-isoaltholactone (66). The opposite enantiomer is a natural product that belongs to the styryllactone family.…”

Pd-Catalyzed Mizoroki-Heck Reactions Using Fluorine-Containing Agents as the Cross-Coupling Partners

“…Moreover, 77 could be easily separated by F-SPE (Fluorous solid phase extraction) technique and reused three times without significant loss of activity. Later, Cai and co-worker developed a PCP Pincer-Pd catalyst (77), which was favorably used in Mizoroki-Heck cross-couplings between perfluoroalkyl alkenes (74) and aryl halides (78) for the preparation of perfluoroalkenylated aryl compounds (79) (Scheme 15) [71]. Due to the unique tridentate coordination architecture, the Pincer complex was stable, selective, and highly reactive, and it permitted low catalyst loadings and gave the possibility of fine-tuning the catalytic properties of the metal center.…”

“…The reaction presumably proceeded via (1) oxidative addition of aryldiazonium salt (106) to Pd(0), leading to an arylpalladium complex (110), (2) (108) were formed as byproducts in most cases [77]. Later, the same research group extended the scope of the heck reaction to other types of fluorine-containing electron-deficient olefins (Scheme 21) [78]. They found that the electronwithdrawing group (EWG) on alkenes had a big influence on the efficacy of the reaction.…”

“…Additionally, changing the fluoroalkyl group from CF3 to CF2H group caused a significant decrease in the chemical yield, although the relatively high regioselectivity was obtained. A plausible reaction mechanism was suggested in Scheme 21 [78]. The reaction presumably proceeded via (1) oxidative addition of aryldiazonium salt (106) to Pd(0), leading to an arylpalladium complex (110), (2) Arylboronic acids are an important class of compounds for coupling reactions, which are stable in air and to moisture, and they are compatible with a broad range of common functional groups [62][63][64].…”