Department of Chemistry, Nara University of Education
Takabatake-cho, Nara 630-8528, Japan
(Last updated 2018/4/1)
We are interested in the development of new efficient reactions and synthetic methods, including use of renewable resources and their application to biologically active compounds and new organic materials. In our research to date, we have shown that ethenetricarboxylate derivatives are highly electrophilic Michael acceptors or electron-deficient C=C components in various synthetic reactions. Lewis acids also promote the reactions of ethenetricarboxylate derivatives efficiently. Novel cyclization and addition reactions gave the compounds shown below.
For example, reaction of allyl ethenetricarboxylates and the amides with Lewis acids such as TiCl4, TiBr4, AlCl3 and AlBr3 gave 3,4-trans halogenomethyl 2-oxotetrahydrofuran and pyrrolidine derivatives stereoselectively in high yields (1). Reaction of 2-substituted 2-propenyl amides with AlCl3 gave 2-oxo-5,6-dehydropiperidines as the major products. The preference for six- over five-membered-ring formation in the reactions of 2-substituted 2-alkenyl substrates has been observed (2).
Intramolecular [2+2] and [4+2] cycloaddition reactions of cinnamylamides of ethenetricarboxylate in sequential processes have been studied. Reaction of 1,1-diethyl 2-hydrogen ethenetricarboxylate and trans-cinnamylamines in the presence of EDCI/HOBt/Et3N led to pyrrolidine products in one pot, via intramolecular [2+2], [4+2] and some other cyclizations. The types of the products depend on the substituents on benzene ring and the reaction conditions (3). The reaction of the amides bearing cyclic ether and acetal groups in the presence of catalytic Lewis acid such as Sc(OTf)3 gave spirocyclic piperidine derivatives as major products. The cyclized products may be formed via intramolecular hydride transfer (4). The scope and limitations of the hydride transfer/cyclization reactions of amides of ethenetricarboxylates was investigated and morpholine formation by intramolecular oxy-Michael addition was also found.
Current Group Members:
Kakeru Go: Masaki Sawada: Mai Yamamoto: Hirotaka Sugiura (Osaka Pref. Univ.)
Representative Recent References:
Lewis Acid Catalyzed Cyclization Reactions of Ethenetricarboxylates via Intramolecular Hydride Transfer, Yamazaki, S.; Naito, T.; Niina, M.; Kakiuchi, K. J. Org. Chem. 2017, 82, 6748−6763.
Intramolecular [2+2] and [4+2] Cycloaddition Reactions of Cinnamylamides of Ethenetricarboxylate in Sequential Processes, Yamazaki, S.; Sugiura, H.; Ohashi, S.; Ishizuka, K.; Saimu, R.; Mikata, Y.; Ogawa, A. J. Org. Chem. 2016, 81, 10863-10886.
Efficient Synthesis of Heterocycles Using Highly Electrophilic Ethenetricarboxylates, Yamazaki, S. Heterocycles, 2016, 92, 1561-1597.
Sc(OTf)3-Catalyzed Cyclization of Allyl Amides of Ethenetricarboxylate, Yamazaki, S; Niina, M.; Kakiuchi, K. Synthesis, 2016, 48, 2889–2895.
Inter- and Intramolecular Diels-Alder Reaction of Ethenetricarboxylate Derivatives, Yamazaki, S.; Sugiura, H.; Niina, M.; Mikata, Y.; Ogawa, A. Heterocycles, 2016, 92, 485-510.
Stereospecific Cyclization Reaction of Alkenyl Esters and Amides of Ethenetricarboxylate, Yamazaki, S.; Wada, J.; Kakiuchi, K. Can. J. Chem. 2015, 93, 1122-1131.
Six-Membered Ring Formation from Lewis Acid Promoted Reactions of 2-Substituted 2-Alkenyl Amides and Esters of Ethenetricarboxylate, Yamazaki, S.; Ueda, K.; Fukushima, Y.; Ogawa, A.; Kakiuchi, K. Eur. J. Org. Chem. 2014, 7023-7033.
Lewis Acid-Promoted Cyclization/Halogenation of Allenyl Ethenetricarboxylates and the Amides: Stereoselective Synthesis of Haloalkenyl Five-membered Heterocycles, Fukushima, Y.; Yamazaki, S.; Ogawa, A. Org. Biomol. Chem. 2014, 12, 3964–3975.
Lewis Acid-Promoted Cyclization Reactions of Alkenyl Ethenetricarboxylates: Stereoselective Synthesis of 2-Oxotetrahydrofurans and 2-Oxopyrrolidines, Yamazaki, S.; Fujinami, K.; Maitoko, Y.; Ueda, K.; Kakiuchi, K. J. Org. Chem. 2013, 78, 8405-8416.