Studies on the enantioselective Heck-Matsuda arylation of N-protected 3-pyrrolines

Author(s)

Danilo Machado Lustosa

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2014-01-12

Examining board members

Carlos Roque Duarte Correia; Fernanda Gadini Finelli; Luiz Carlos Dias

• Advisor: Carlos Roque Duarte Correia

Abstract

The conventional Heck reaction consists of a reaction between olefins and vinyl or aryl halides catalyzed by palladium. The variant Heck-Matsuda (HM) uses arenediazonium salts, more reactive than the corresponding aryl or vinyl halides. For a long time the HM was seeing as a limited synthetic method due to the absence of its enantioselective version. In 2012, the group of prof. Carlos Correia reported the first enantioselective Heck-Matsuda reaction. Aiming at making this methodology a powerful synthetic tool, as well as to get mechanistic insights, this dissertation describes our studies on the enantioselective HM employing chiral, non-racemic, palladium complexes for the arylation of 3-N-protected- pyrrolines. With the use of Pd/pyridine-oxazoline complexes chiral Heck adducts were obtained containing electron rich substituents in good to excellent yields in enantiomeric ratios from moderate to good. When making use of arenediazonium salts with electron withdrawing substituents, the Heck adducts were obtaining in low from good yields in enantiomeric ratios from good to excellent. Some of the Heck adducts were selected in order to synthesize baclofen analogues and butyrolactams to demonstrate not only the applicability of the new method but also to determine the absolute stereochemistry of the Heck adducts (comparison of our [a]D values with those reported in the literature). Finally, with the absolute stereochemistry of the products determined, a rationale for this new enantioselective Heck-Matsuda was provided (AU)

• FAPESP's process: 12/18360-0 - Studies on the enantioselective Heck-Matsuda arylation of N-protected 3-pyrroline and the evaluation of phosphite-oxazolines as ligands.
• Grantee: Danilo Machado Lustosa
• Support Opportunities: Scholarships in Brazil - Master