Study and synthetic application of the Heck-Matsuda arylation of dehydrohydroxy esters and dehydroamino esters

Author(s)

Francisco de Azambuja

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2010-02-24

Examining board members

Carlos Roque Duarte Correia; Sergio Pinheiro; Fernando Antonio Santos Coelho

• Advisor: Carlos Roque Duarte Correia

Abstract

The arylation of 2-acetoxy or acetamido substituted acrylates was studied through the Heck reaction with arenediazonium salts. After evaluation of the catalyst, solvent, temperature and acidity of the reaction medium, methyl 2-acetoxyacrylate was arylated with p-methoxyphenyldiazonium tetrafluoroborate under Pd2dba3 catalysis, with 2,6-di-terc-butyl-4-methylpyridine as base in benzonitrile at 110 °C for 3 hours. The Heck adduct was obtained in 59 % of yield. Other diazonium salts did not furnished the expected adducts in good yields. Methyl 2-acetamidoacrylate arylation occurred in methanol at 65 °C, using Pd(OAc)2 as catalyst and 2,6-di-terc-butyl-4-methylpyridine as base. Yields between 24-73 % were observed using diazonium salts substituted with iodine, fluoro, methoxy or nitro groups, besides 2-naphthyl or benzenediazonium tetrafluoroborate. The lower yields were by-passed through methyl 2-trifluoroacetamidoacrylate arylation, under the same conditions, resulting in yields between 65-86 % for the same electrophiles. The aza-2-methoxylated adducts obtained were submitted to an elimination/reduction or alkylation protocol using BF3.OEt2 and silane nucleophiles. The protected phenylalanine derivatives were obtained in low to good yields and represent an alternative to prepare unnatural amino acids, a-substituted or not. A one-pot version of this reduction was briefly studied through triethylsilane hydride addition in the Heck reaction. The efficiency of this reaction was comparable with the two-step protocol (AU)

• FAPESP's process: 08/01985-2 - Study and synthetic application of Heck-Matsuda arylation with dehydrohidroxy esters and dehydroamino esters
• Grantee: Francisco de Azambuja
• Support Opportunities: Scholarships in Brazil - Master