Fukuyama吲哚合成反应是由東京大学的福山透等人发现的自由基环化反应，可实现多取代吲哚的合成，分为第一代合成法和第二代合成法。通常用三丁基氢化锡作为自由基还原剂、AIBN或三乙基硼为自由基引发剂。该反应可用于合成含多取代吲哚结构的天然产物，如 aspidophytine、长春花碱和番木鳖碱，2002年，福山首次实现长春花碱的全合成。

第一代：异腈法

【J. Am. Chem. Soc. 1994, 116, 3127】 

第二代：异硫氰酸酯法

【J. Am. Chem. Soc. 1999,121, 3791】

特别是第二代方法，是引入多种取代基的有效方法 。在2位的sp3碳原子上引入基团（通过偶联反应通常不能实现）。

原料的硫氰酸酯，可由喹啉的开环反应制备，反应简便易行，并能应用于大量合成。

另外还可以通过2-卤代苯胺和炔进行Sonogashira偶联反应，得到芳基炔，在通过锌粉还原得到2-烯基苯胺，再和硫光气反应生成硫氰酸酯。

反应机理

两种方法都是由自由基环化机理进行的。烯烃是反式构型时，热力学稳定的六元环副产物（四氢喹啉）会增加。

＜第一代＞

＜第二代＞

反应实例

本吲哚合成是合成(+)-Vinblastine中至关重要的步骤,是有機合成化学金字塔中的一个经典实例。

Thioanilide 11 (43.3g, 75.0 mmol), tri-n-butyltin hydride (22.2 mL, 82.5 mmol) and 2,2’- azobisisobutyronitrile (1.23 g, 7.50 mmol) were dissolved in 3.0 L of toluene at room temperature. After bubbling of argon gas for 10 min, the resulting solution was heated to 110 °C and stirred for 10 min. After cooling to room temperature, to the resulting suspension was added 1.0 L of half-saturated aqueous potassium fluoride. The resulting two-phase mixture was stirred vigorously for 3 h. After removal of the organic layer, the aqueous layer was extracted with ethyl acetate twice. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered through a pad of Celite and concentrated in vacuo to give ca. 75 g of crude syrup. Another 22.3 g (38.6 mmol) of thioanilide was converted to ca. 60 g of crude indole in the same manner. These two crude indole was combined and purified with flash chromatography (SiO2 600 g, 20-40% ethyl acetate in hexane) to give 49.3 g (90.4 mmol, 79.6%) of acceptably pure indole 12 as a slightly yellow oil. A small amount of 12 was purified with preparative thin layer chromatography. This material was obtained as a mixture of two diastereomers.

【J. Am. Chem. Soc. 2002, 124, 2137】