Padwa A, Brodney M A, Dimitroff M, Liu B, Wu T
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
J Org Chem. 2001 May 4;66(9):3119-28. doi: 10.1021/jo010020z.
A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels--Alder cycloaddition reaction (IMDAF) of furanyl carbamates bearing tethered alkenyl groups. The initially formed [4 + 2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. A synthetic route to (+/-)-mesembrane and (+/-)-crinane was accomplished using this methodology. It was possible to carry out a stereoselective reduction of the initially formed hexahydroindolinone ring to produce the cis-3a-aryl-hydroindole skeleton. A related [4 + 2]-cycloaddition/rearrangement sequence was also used for a formal synthesis of the Chinese ornamental orchid (+/-)-dendrobine. The tricyclic alkaloid core was formed stereoselectivity from the thermolysis of N-[(2-methyl-2-cyclopentenyl)methyl]-N-(4-isopropyl-furan-2-yl)carbamic acid tert-butyl ester. Kende's advanced intermediate 33 was prepared in seven additional steps by standard transformations, thereby completing a formal synthesis of (+/-)-dendrobine.
通过带有连接烯基的呋喃基氨基甲酸酯的分子内狄尔斯-阿尔德环加成反应（IMDAF），实现了各种取代六氢吲哚酮的便捷合成。最初形成的[4 + 2]环加成物经历氮辅助的开环，随后对所得两性离子进行去质子化，得到重排的酮。IMDAF环加成的立体化学结果是，连接烯基的侧链相对于氧桥呈顺式取向。使用该方法完成了（±）-膜萼马钱子碱和（±）-长春花碱的合成路线。对最初形成的六氢吲哚酮环进行立体选择性还原，以生成顺式-3a-芳基-氢化吲哚骨架是可行的。一个相关的[4 + 2]环加成/重排序列也被用于中国观赏兰花（±）-石蒜碱的形式合成。三环生物碱核心由N-[(2-甲基-2-环戊烯基)甲基]-N-(4-异丙基-呋喃-2-基)氨基甲酸叔丁酯的热解立体选择性地形成。通过标准转化，再经过七个额外步骤制备了肯德的高级中间体33，从而完成了（±）-石蒜碱的形式合成。
