Gabriele Bartolo, Mancuso Raffaella, Salerno Giuseppe, Lupinacci Elvira, Ruffolo Giuseppe, Costa Mirco
Dipartimento di Scienze Farmaceutiche, Università della Calabria, 87036 Arcavacata di Rende (Cosenza), Italy.
J Org Chem. 2008 Jul 4;73(13):4971-7. doi: 10.1021/jo8006495. Epub 2008 Jun 10.
1-(2-Aminoaryl)-2-yn-1-ols, easily obtained by the Grignard reaction between 1-(2-aminoaryl)ketones and alkynylmagnesium bromides, were subjected to carbonylative conditions in the presence of the PdI2-KI catalytic system, in the presence and in the absence of an external oxidant. Under oxidative conditions (80 atm of a 4:1 mixture of CO-air, in MeOH as the solvent at 100 degrees C and in the presence of 2 mol % of PdI2 and 20 mol % of KI), 1-(2-aminoaryl)-2-yn-1-ols bearing a primary amino group were selectively converted into quinoline-3-carboxylic esters in fair to good yields [45-70%, based on starting 1-(2-aminoaryl)ketones], ensuing from 6-endo-dig cyclization followed by dehydration and oxidative methoxycarbonylation. On the other hand, indol-2-acetic esters, deriving from 5-exo-dig cyclization followed by dehydrating methoxycarbonylation, were selectively obtained in moderate to good yields [42-88%, based on starting 1-(2-aminoaryl)ketones] under nonoxidative conditions (90 atm of CO, in MeOH as the solvent at 100 degrees C and in the presence of 2 mol % of PdI2 and 20 mol % of KI), in the case of 1-(2-aminoaryl)-2-yn-1-ols bearing either a primary or secondary amino group and substituted with a bulky group on the triple bond.
1-(2-氨基芳基)-2-炔-1-醇可通过1-(2-氨基芳基)酮与炔基溴化镁之间的格氏反应轻松制得，在PdI₂-KI催化体系存在下，于有或无外部氧化剂的情况下进行羰基化反应。在氧化条件下（4:1的CO-空气混合物80个大气压，以甲醇为溶剂，100℃，存在2 mol%的PdI₂和20 mol%的KI），带有伯氨基的1-(2-氨基芳基)-2-炔-1-醇通过6-内型环化，随后脱水和氧化甲氧基羰基化，以中等至良好的产率[基于起始的1-(2-氨基芳基)酮为45-70%]选择性地转化为喹啉-3-羧酸酯。另一方面，在非氧化条件下（90个大气压的CO，以甲醇为溶剂，100℃，存在2 mol%的PdI₂和20 mol%的KI），对于在三键上带有伯氨基或仲氨基且被庞大基团取代的1-(2-氨基芳基)-2-炔-1-醇，通过5-外型环化，随后脱水甲氧基羰基化，可选择性地以中等至良好的产率[基于起始的1-(2-氨基芳基)酮为42-88%]得到吲哚-2-乙酸酯。
