Estudo da reação de arilação de Heck de enecarbamatos, enamidas e enoleteres endociclicos utilizando sais de diazonio

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

The Heck arylation of olefins with aryltriflates and arylhalides is a well-established synthetic methodology for C-C bond formation. The Heck arylation employing diazonium salts (Heck-Matsuda reaction) is a much less explored methodology but offers a number of advantages over the traditional Heck protocol. These advantages comprise its mildness, shorter reaction times, and phosphine-free conditions. Despite several applications of the Heck reaction to the synthesis of a number of biologically important heterocycles and alkaloids by our research a systematic investigation of this reaction was still needed. Therefore, we decided to carry out a study to probe the scope of the Heck arylation with aryldiazonium tetrafluoroborates employing endocyclic enecarbamates, enamides e enol ethers as olefin partners. We also tested several different reaction variables in order to find optimum reaction conditions. First, a series of endocyclic enecarbamates, enamides and enolethers of varying ring size were synthesized and submitted to the Heck-Matsuda arylation. Also examined were: the stoichiometry of reaction, the eletronic characteristic of the substituents on the diazonium salt, the catalyst, the amount of catalyst used, the temperatura, the solvente and the use of additives. For the five-membered enecarbamate, we noticed that yields of the Heck reaction depend on the nature of the aryldiazonium salt. Yields are usually good to hight (60-86%) with electron-donating substituents on aryldiazonium salt (R=OMe, H, Me), whereas electron-withdrawing groups (R=Cl, F) led to a decrease in yields (8-40%). For enamides yields ranged from good to excellent (75-90%) when R=OMe, Me, H or Cl. Strong electron-withdrawing groups such as fluor led to a sharp decrease in yields (40%). No reaction was observed when R=NO2 or CO2Me. Endocyclic enolethers reacted smoothly with aryldiazonium salts bearing electron-donating substituents (95-98% for R=OMe, H). However no reaction was observed when R=Cl, NO2 or CO2Me. Six-membered endocyclic enecarbamates were equally reactive but contrary to five membered enecarbamates they provided mixtures of regioisomer in variable ratios. Several reaction conditions had been tested in an attempt to control the isomerization of the double bond, with only moderate success. The use of paladacycle, at 110°C , gave the arylated enecarbamate as the major Heck adduct. Six-membered enolethers were as reactive as six-membered enecarbamates toward arylation. Seven-membered enecarbamates behaved similarly to five-membered enecarbamates. Heck arylation with diazonium salts afforded essencially a single regioisomer in good to excelente yields (72-97%). Heck arylation of the electron rich enecarbamates, enamides and enolethers with aryldiazonium salts is an effective arylation protocol with great synthetic potencial. With exception of six-membered system, Heck arylations produced a single regioisomeric adduct in good to excellent yields. Enecarbamates are more sensitive to electronic nature of the substituent on the aryldiazonuim salts, whereas the less electron-rich enamides and enol ethers seem less sensitive to such effects. The results obtained in this study had also allowed a better comparison between Heck arylation with diazonium salts and Heck arylation with halides and trifates. We observed strong indications that the Heck arylation with electron-rich olefins involves a ionic mechanism, with the participation of a cationic palladium intermediate, partially stabilized for the solvent.

ASSUNTO(S)

compostos organicos arilação reação de adição

ACESSO AO ARTIGO

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