Yamaguchi酯化反应

该反应最早是由日本九州大学的Masaru Yamaguchi在1979年报道的。

羧酸和2,4,6-三氯苯甲酰氯作用生成混酐使羧酸得以活化，继而在DMAP的催化下与醇反应生成酯。该反应既可以用于普通酯的生成，也可以用于内酯的生成。对于大环内酯的生成尤为有效，所以在现代天然产物全合成研究中得到非常广泛的应用。

在合成大环内酯时，先与2,4,6-三氯苯甲酰氯作用后生混酐后，加入DMAP在高稀释条件下进行大环内酯化的反应。比Corey-Nicolaou法的活性要高，但通常也需要加热回流。

The aliphatic carboxylate adds to the carbonyl carbon of Yamaguchi reagent, forming a mixed anhydride, which is then attacked by DMAP regioselectively at the less hindered carbon, producing acyl-substituted DMAP. This highly electrophilic agent is then attacked by the alcohol to form the product ester.

The in situ formation of the symmetric aliphatic anhydride is proposed to explain the regioselectivity observed in the reactions of aliphatic acids, based on the fact that aliphatic carboxylates are more nucleophilic, and aliphatic anhydrides are more electrophilic towards DMAP and alcohol than their counterparts.

标签： macro-lactones