Heck arylations with diazonium salts: methodology and applications in the synthesis of chiral ligands, natural products and analogues

Author(s)

Angélica Venturini Moro

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2010-04-16

Examining board members

Carlos Roque Duarte Correia; Alessandro Bolis Costa Simas; Adriano Lisboa Monteiro; Paulo Cesar Muniz de Lacerda Miranda; Antonio Claudio Herrera Braga

• Advisor: Carlos Roque Duarte Correia

Abstract

The present work was centered in the Heck arylation of several olefins with diazonium salts and application of the arylated products in the syntheses of chiral ligands, natural products and analogues. In studies involving the Heck arylation of styrenes with diazonium salts an efficient, short, regio- and stereoselective synthesis of resveratrol, DMU-212 and analogues was developed. In the Heck reaction of allylic esters with diazonium salts high chemo-, regio- and stereoselectivity was obtained. The arylated allylic esters were synthesized in high yields and with retention of the traditional leaving group. Moreover, the arylation of cyclic allylic esters was developed, and the products were used in the total synthesis of natural kavalactones. The total synthesis of (-)-isoaltholactone was successfully accomplished in 12 steps in 13 % overall yield. The key-step involved highly stereoselective Heck arylation between the phenyldiazonium salt and chiral dihydrofuran. The phenyl group was introduced with high diastereoselectivity and had a crucial role in directing the formation of the remaining stereocenters of the molecule. In the studies towards the synthesis of aza-altholactone, unexpected difficulties were found in some steps, particularly in the oxidation of alcohols to aldehydes by traditional protocols. These problems were circumvented by changing the synthetic route, but additional problems were found in the lactonization and hampered the obtention of the aza-altholactone, until the present moment. New chiral amino alcohols were synthesized by arylation of enecarbamates with diazonium salts. These compounds were used as chiral ligands in the catalytic asymmetric arylation of aldehydes and the diarylmethanols were prepared in high yields and enantiomeric excesses. (AU)

• FAPESP's process: 05/05150-4 - Study of Heck arylation reaction of non-activated olefins with diazonium salts and their application in stereo controlled total synthesis of neuro excitatory amino acids of the acromelate family
• Grantee: Angélica Venturini Moro
• Support Opportunities: Scholarships in Brazil - Doctorate