Highly regioselective Friedlander annulations with unmodified ketones employing novel amine catalysts: Syntheses of 2-substituted quinolines, 1,8-naphthyridines, and related heterocycles

被引：143

作者：

Dormer, PG ^{[1
]}

Eng, KK ^{[1
]}

Farr, RN ^{[1
]}

Humphrey, GR ^{[1
]}

McWilliams, JC ^{[1
]}

Reider, PJ ^{[1
]}

Sager, JW ^{[1
]}

Volante, RP ^{[1
]}

机构：

[1] Merck & Co Inc, Dept Proc Res, Rahway, NJ 07065 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2003年 / 68卷 / 02期

关键词：

D O I：

10.1021/jo026203i

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Catalysts were evaluated on the preparation of 2-substituted quinolines, 1,8-naphthyridines, and chromone derivatives from unmodified methyl ketones and o-aminoaromatic aldehydes. While oxide catalysts yielded the 2,3-dialkyl substituted products, cyclic secondary amines provided the 2-alkylsubstutited products regioselectively. In particular, pyrrolidine derivatives provided the highest regioselectivity favoring the 2-substituted products. The most reactive and regioselective catalyst was the bicyclic pyrrolidine derivative, TABO (1,3,3-trimethyl-6-azabicyclo[3.2.1] octane), yielding 1,8-naphthyridines with as high as 96:4 regioselectivity. Regioselectivity increased with slow addition of the methyl ketone substrate to the reaction mixture, and was positively related to temperature. Isolated yields of single regioisomers were typically 65-84%, while observed regioselectivities were greater than or equal to90:10 for 1,8-naphthyridines and greater than or equal to84:16 for quinolines.

引用

页码：467 / 477

页数：11

共 41 条

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