Synthesis of multisubstituted phenols by formal [4 + 2] cycloaddition of nucleophilic alkynes with 3-ethoxycyclobutanones

Abstract

Nucleophilic alkynes bearing sulfonamide, trimethylsilyl, or p-methoxyphenyl groups at the sp carbon reacted with 3-ethoxycyclobutanones to give formal [4 + 2] cycloadducts by activation with TiCl. Reactions with 2-monoalkyl and 2-nonsubstituted 3-ethoxycyclobutanones gave phenol derivatives directly by benzannulation, while the use of 2,2-dimethyl-3-ethoxycyclobutanone gave the corresponding dienones, which were converted to pentasubstituted phenols by dienone-phenol rearrangement. Regioselectivity that depended on the activation conditions of dienone-phenol rearrangement is also described.

Cleavage of Carbon–Carbon σ-Bonds of Four-Membered Rings

“…Discussed herein are only examples reported afterward (Table ). 3-Alkoxycyclobutanone 287 undergoes formal (4 + 2) cycloaddition reactions with quinoline 291 , azobenzene 293 , and ynamide 295 . A reaction of α-monosubstituted alkoxycyclobutanone 297 with nitorosobenzene 298 was developed as well .…”

“…3-Alkoxycyclobutanone 287 undergoes formal (4 + 2) cycloaddition reactions with quinoline 291, 136 azobenzene 293, 137 and ynamide 295. 138 A reaction of α-monosubstituted alkoxycyclobutanone 297 with nitorosobenzene 298 was developed as well. 139 3-Arylcyclobutanone 300 undergoes a (4 + 2) cycloaddition reaction with nitriles.…”

Ring forming transformations of ynamides via cycloaddition

“…During the last decade, extensive work on ynamides revealed their attractive synthetic features and broad application spectrum that considerably stimulated the development of the asymmetric synthesis of Nheterocycles. [110][111][112][113][114][115][116][117][118] In addition to this, the synthetic applications of the developed methodologies for the total synthesis of natural products with biological and optoelectronic properties have been achieved. [119][120][121] Further the application of the transformations could be extended for the synthesis of biologically active and pharmaceutical molecules via late-stage functionalization.…”

Regioselective Rearrangement of 4,4-Disubstituted 2-Hydroxycyclohexa-2,5-Dienones under Deoxyfluorination Conditions

“…The dienone-phenol rearrangement is a powerful tool for the synthesis of multisubstituted phenols that are not readily available by conventional aromatic substitution chemistry . Its application to spiro compounds provides easy access to polycyclic structures by ring expansion of the spirocyclic system .…”