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세미나1.

제  목 :  Asymmetric hetero-Michael reaction of α,β-unsaturated carboxylic acid derivatives

연  사 : Yoshiji Takemoto (Graduate School of Pharmaceutical Sciences, Kyoto University)
 

일  시 : 2014년 11월 3일 (월) 오후 4시 30분

장  소 : 화학관 세미나실 (330226호실)

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 Asymmetric hetero-Michael reaction of α,β-unsaturated
carboxylic acid derivatives

              

     Chiral oxygen-containing heterocycles such as isoxazolines, isoxazolidines, chromans, and dihydrobenzofurans can be found in numerous natural products and biologically active compounds. O-Heterocycles bearing amide moiety, in particular, such as roxifiban and erythrococcamide, exhibit pharmaceutically important activities, and the related carboxylic acids, such as acivicin and raxofelast, have been used as biological tools for drug discovery.
Significant efforts have been focused on development of synthetic methods capable of providing facile access to these materials, but no successful reactions with unsaturated amides and carboxylic acids have been reported. Bifunctional hydrogen bond (HB)-donor organocatalysts have now come to represent a particularly promising approach to accomplish
highly enantioselective reactions, although there is still a strong drive to improve upon their catalytic activities and expand the scope of applicable reactions. We envisaged that improvements to the HB-donating ability could activate the poorly reactive Michael acceptor, and that this would be more important for an effective cyclization than increasing the basicity
of the catalyst to activate the O-nucleophile.
     In the lecture, we report the asymmetric intramolecular oxa-Michael (AIOM) reaction of unactivated α,β-unsaturated amides and esters using powerful HB-donor organocatalysts.1)
Furthermore, the products obtained from this reaction have been used for the straightforward
asymmetric synthesis of several natural products and biologically important compounds.

     We will also describe a new synthetic method for the AIOM reaction of α,β-unsaturated carboxylic acids using a dual arylboronic acid-aminothiourea catalytic system. We found that aminoboronic acid could be used to facilitate the intramolecular aza- and oxa-Michael reactions of α,β-unsaturated carboxylic acids. In addition, the combination of an arylboronic acid with a chiral aminothiourea provided the desired heterocycles in high yields and ee’s.2)
The overall utility of this dual catalytic system was demonstrated by a one-pot enantioselective synthesis of (+)-erythrococcamide B, which proceeded via sequential Michael and amidation reactions.