Organocatalytic Asymmetric Michael Addition of Aliphatic Aldehydes to Indolylnitroalkenes: Access to Contiguous Stereogenic Tryptamine Precursors
有机催化的脂肪醛对吲哚硝基烯的不对称Michael 加成反应：制备相邻手性中心的色胺衍生物 Jian Chen(陈坚), Zhi-Cong Geng(耿智聪), Ning Li(李宁), Xiao-Fei Huang(黄晓飞), Feng-Feng Pan(潘锋锋), and Xing-Wang Wang(王兴旺)*
J. Org. Chem.2013, 78, 2362-2372.
Because of the importance of the indole framework and the versatile transformation of nitro and formyl groups, the efficient synthesis of optically pure 2-alkyl-3-(1H-indol-3-yl)-4-nitrobutanals, one type of tryptamine precursors are of great interest for pharmaceutical and biological research. Herein, the Michael addition of aliphatic aldehydes to indolylnitroalkenes has been developed using (S)-diphenylprolinol trimethylsilyl ether as an organocatalyst, which provides the desired optically pure syn 2-alkyl-3-(1H-indol-3-yl)-4-nitrobutanal derivatives in up to 98% yield with up to >99:1 dr and >99% ee. To show the synthetic usefulness of this methodology, optically active 2-alkyl-4-nitro-3-(1-tosyl-1H-indol-3-yl)butan-1-ol and tryptamine derivatives are readily obtained by stepwise systematic transformations.
