《ART》章末总结7

《ART》第七章，用几道习题来结束这本书吧。

Chapter VII

2. The following sequence of reactions was reported recently as part of a synthesis of the natural product qinghaosu, the active ingredient in a number of Chinese folk medicines. Qinghaosu is an antimalarial drug, a property of increasing importance as new strains of malaria appear that are resistant to the drugs that have been used until now.

The compound in brackets has been shown to be an intermediate in the conversion of the hydroperoxide to the endoperoxide. Air is not required for its formation. In fact, it is isolable at low temperatures (-20 °C) when air is excluded. If it is then exposed to air, it is transformed to the endoperoxide.

Draw mechansisms for each of the steps in this sequence. Your mechanisms should take the preceding information into account.

Ans

首先来看第一步，条件是 氧气 + Rose Bengal + 光照。氧气在基态情况下是以 triplet oxygen 存在的，因此在 autoxidation 过程中作为 diradical 发挥作用，但是此处的光照和 Rose Bengal（即酸性红94，常作为光敏剂）是经典的生成 singlet oxygen 条件，因此该反应的机理即为单线态氧参与的 Ene reaction。

接着，题干提示第二步转化的中间体不需要空气存在，这说明重排过程中没有额外氧气分子引入，中间体的两个氧均来自于反应物。

然后中间体进一步转化为过氧产物，这一步显然需要外部氧气存在，机理是经典的 autoxidation 类型，生成的 hydroperoxidation product 通过极性机理生成半缩醛。

最后是形成半缩醛和酯化的两步串联反应。

4. The technology used in the preparation of isocomene can be modified to carry out several other interesting transformations.

(a) Draw mechanism for each transformation from 1 to 4.

Ans

本题摘出来主要是为了讨论从 3 至 4 的转化。

注意该反应中使用了 2 当量的三丁基锡氢，很容易想到第一当量的自由基环化反应，通过 5-exo-trig 环化生成五元桥环。我们还注意到左侧三元环打开了，结合一旁的羰基结构，我们推测可能是通过羰基碳自由基的 β-scission 开环的，因而第二当量三丁基锡氢的作用就呼之欲出了。

5. Draw a reasonable mechanism for each step in the following synthesis sequence.

Ans

d