From Chiral ortho-Benzoquinone Monoketals to Nonracemic Indolinocodeines through Diels–Alder and Cope Reactions

The S-dienol (−)-4 containing 10 carbons and one oxygen of the final product was prepared in 98.6% ee and 39% yield from cyclohexan-1,3-dione. It was attached to the aromatic ring as a monoether of catechol S-(−)-6 and subsequently subjected to oxidative ketalization in methanol. The allylated phenanthrofuran obtained was selectively oxidized at the terminal double bond. The fifth ring was completed by a “one-pot” amidation–cyclization process promoted by palladium acetate. The final homochiral indolinocodeine (−)-31 was obtained in 16 steps and 3.6% overall yield from cyclohexan-1,3-dione.

以环己烷-1,3-二酮为起始原料，以98.6%的对映体过量（enantiomeric excess, ee）和39%的产率制备得到了目标产物中含10个碳原子与1个氧原子的(-)-4号S-二烯醇（S-dienol）。将其作为儿茶酚（catechol）S-(-)-6的单醚连接至芳香环上，随后在甲醇中进行氧化缩酮化反应。所得烯丙基化菲并呋喃在末端双键处发生选择性氧化。通过乙酸钯（palladium acetate）促进的一锅法酰胺化-环化过程完成了第五个环的构建。从环己烷-1,3-二酮出发，经16步反应，以3.6%的总产率得到了最终的手性纯吲哚啉可待因（indolinocodeine）(-)-31。