Synthesis of Benzodihydrofurans by Asymmetric C-H Insertion Reactions of Donor/Donor Rhodium Carbenes
Synthesis of Benzodihydrofurans by Asymmetric C-H Insertion Reactions of Donor/Donor Rhodium Carbenes
复制标题
DOI：
10.1002/chem.201701630
复制
发表时间：
2017-09-04
影响因子：
4.3
通讯作者：
Shaw, Jared T.
中科院分区：
文献类型：
--
作者：
Lamb, Kellan N.;Squitieri, Richard A.;Shaw, Jared T.
附加有两个给电子基团的金属卡宾（称为供体/供体卡宾）与醚底物发生非对映和对映选择性铑催化的 C-H 插入反应，形成苯并二氢呋喃。与连接有吸电子基团的金属卡宾的反应不同，亲电子性减弱使得这些反应能够在路易斯碱性溶剂（例如乙腈）和水存在下进行。这些物质的重氮前体是使用温和的化学选择性氧化剂 (MnO2) 由腙原位制备的。尽管这一序列通常可以在一锅中进行，但对照实验已经阐明了为什么两锅法通常更有效。对非手性催化剂的彻底筛选表明，空间阻碍催化剂是非对映选择性反应的最佳选择。尽管观察到烯丙基和炔丙基 C-H 键的有效插入，但注意到某些底物存在竞争性偶极环加成过程。描述了这种有用的苯并二氢呋喃合成方法的完整底物范围、副反应机制以及立体选择性起源的计算支持。
Metal carbenes appended with two electron-donating groups, known as donor/donor carbenes, undergo diastereo- and enantioselective rhodium-catalyzed C-H insertion reactions with ether substrates to form benzodihydrofurans. Unlike the reactions of metal carbenes with electron-withdrawing groups attached, the attenuated electrophilicity enables these reactions to be conducted in Lewis basic solvents (e.g., acetonitrile) and in the presence of water. The diazo precursors for these species are prepared in situ from hydrazone using a mild and chemoselective oxidant (MnO2). Although this sequence often can be performed in one-pot, control experiments have elucidated why a two-pot process is often more efficient. A thorough screening of achiral catalysts demonstrated that sterically encumbered catalysts are optimal for diastereoselective reactions. Although efficient insertion into allylic and propargylic C-H bonds is observed, competing dipolar cycloaddition processes are noted for some substrates. The full substrate scope of this useful method of benzodihydrofuran synthesis, mechanisms of side reactions, and computational support for the origins of stereoselectivity are described.