Wang Lihong, Prabhudas Bodhuri, Clive Derrick L J
Chemistry Department, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
J Am Chem Soc. 2009 Apr 29;131(16):6003-12. doi: 10.1021/ja900857h.
A detailed study has been made of a method of ring closure categorized as an all-carbon intramolecular conjugate displacement (ICD). This reaction involves intramolecular addition of a carbanion, which is stabilized by at least one electron-withdrawing group, to a Michael acceptor which has a leaving group in an allylic position. The process formally resembles a combination of Michael addition and S(N)2' displacement. The overall result is formation of a ring with loss of the allylic leaving group and shift of the original double bond to a new location spanning the positions of the electron-withdrawing substituent of the Michael acceptor subunit and the original allylic leaving group. The starting materials are easily prepared by a selenium-based version of the Morita-Baylis-Hillman reaction. The cyclizations are transition metal free and occur under mild conditions, using DBU or Cs(2)CO(3) in MeCN or THF. Acetate is a suitable leaving group and the electron-withdrawing substituent of the Michael acceptor unit can be CO(2)R, SO(2)Ph, or CN. Six- and seven-membered rings are formed efficiently, and complex structures, such as those resembling the core of CP-225,917, are easily assembled. The products of these ICD reactions are themselves classical Michael acceptors. A range of mechanisms probably operates, depending on the structure of the starting material and the reaction conditions, but conclusive evidence for a stepwise mechanism was obtained in a suitably biased case, while other observations are compatible with a concerted process or a stepwise path involving a short-lived carbanion that evades capture by a proton source.
对一种归类为全碳分子内共轭位移（ICD）的环化方法进行了详细研究。该反应涉及一个碳负离子的分子内加成，该碳负离子由至少一个吸电子基团稳定，并加成到一个在烯丙基位置带有离去基团的迈克尔受体上。该过程在形式上类似于迈克尔加成和S(N)2'位移的组合。总体结果是形成一个环，同时烯丙基离去基团离去，原始双键转移到一个新位置，跨越迈克尔受体亚基的吸电子取代基和原始烯丙基离去基团的位置。起始原料可通过基于硒的森田-贝利斯-希尔曼反应轻松制备。环化反应无需过渡金属，在温和条件下进行，使用DBU或碳酸铯在乙腈或四氢呋喃中。乙酸盐是合适的离去基团，迈克尔受体单元的吸电子取代基可以是CO(2)R、SO(2)Ph或CN。六元环和七元环能高效形成，复杂结构，如那些类似于CP-225,917核心的结构，也能轻松组装。这些ICD反应的产物本身就是典型的迈克尔受体。可能存在一系列机制，这取决于起始原料的结构和反应条件，但在一个适当偏向的情况下获得了逐步机制的确凿证据，而其他观察结果与协同过程或涉及一个逃避质子源捕获的短寿命碳负离子的逐步路径相一致。
