Synthesis of Substituted Coumarins and 2‐Quinolinones by Cycloisomerisation of (Hydroxy/aminophenyl)propargyl Alcohols

Abstract

A new cycloisomerization strategy for the synthesis of coumarins and quinolinones is described. The addition of ethoxyacetylide to 2‐hydroxyacetophenones directly resulted in 4‐substituted coumarins by 6‐endo‐dig cycloisomerisation of the intermediate 3‐ethoxy‐1‐(2‐hydroxyphenyl)‐2‐propyn‐1‐ols. Under similar conditions, 2‐aminoacetophenone produced 2‐ethoxyquinoline, a masked quinolinone, which was converted into the quinolinone by acid treatment. N‐Protected intermediate 8 was isolated and converted into the quinolinone [with In(OTf)3 or H2SO4] or the 3‐iodo‐2‐quinolinone (with I2 and H+).

Recent Advances in Synthesis of 4-Arylcoumarins

“…In 2012, Reddy et al proposed an interesting method for the formation of the C(3)–C(4) double bond and O(1)–C(2) ester bond of 4-arylcoumarins by acetylide addition and subsequent cycloisomerization [ 89 ] ( Scheme 12 ). Treatment of 2-hydroxybenzophenone 65 with ethoxyacetylide provided propargyl alcohol intermediate 67 .…”

Carbonylative annulation of unsaturated compounds using molybdenum hexacarbonyl: an efficient synthesis of 2(1H)-quinolones

“…37 Thus, general and versatile synthetic methods for construction of these interesting frameworks are of great interest in synthetic organic chemistry. Although various classic methodologies exist for construction of 2-quinolinones, [38][39][40][41][42][43][44][45][46][47] their utility in construction of 3,4-disubstituted quinolones are limited and they usually lead to monosubstituted scaffolds. On the other hand, only few examples of metal-catalyzed strategies which provide more powerful and practical route to heterocycles, are reported for construction of substituted quinolones.…”