P-26 キラルアミン反応剤を用いる不斉Michael付加反応の開発と(+)-negamycinへの応用(ポスター発表の部)

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We investigated Michael addition of chiral amine (-)-2 derived from (+)-10-ketopinic acid as a part of our studies on the asymmetric Michael addition. After scrutinizing the reaction condition using tert-butyl cinnamate as a Michael acceptor, it was found that solvents and additives crucially affected both chemical yields and stereoselectivities. Namely, the reaction attained in THE afforded the ester of (S)-β-amino acid derivative 4A in good yield and with satisfied diastereomeric excess while adding lithium triflate into the reaction medium increased in the yield and the diastereoselectivity. Surprisingly, the reaction conducted in Et_2O gave the ester of (R)-β-amino acid derivative 4B. Further studies revealed that the Michael addition was applicable to various α,β-unsaturated esters to give esters of β-amino acids in 73-90 % yield within 87-99 %de (Table 2). Fortunately oxidation of tertiary amine with NIS or deprotection of benzyl group by hydrogenolysis and following regioselective oxidation of secondary amines with NIS proceeded without loss of stereochemical integry to furnish β-amino esters 5 with >99 %ee in good yield (Table 3). Finally, we report the synthetic application to the asymmetric total synthesis of (+)-Negamycin (Scheme 4).
天然有機化合物討論会の論文
2007-08-24