Isomerization coupling

Likewise, an efficient one-pot multicomponent synthesis of annelated 2-amino pyridines (e.g., 17) utilizing [4+2] cycloadditions has been described <06JOC3494>. The process involves the in situ generation of 1-aza-1,3-butadiene from a palladium-catalyzed coupling-isomerization reaction of aryl halides (e.g., 18) with propargyl V-tosylamines (e.g., 19). The resulting butadiene then undergoes cycloadditions with V.S -ketene acetals (e.g., 20) to form annelated pyridines (e.g., 17). 

Palladium-catalyzed cyclization reactions with aryl halides have been used to synthesize pyrazole derivatives. V-Aryl-lV-(c>-bromobenzyl)hydrazines 26 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2W-indazoles 27 . Palladium-catalyzed cascade intermolecular queuing-cyclocondensation reaction of o-iodophenol (28) with dimethylallene and aryl hydrazines provided pyrazolyl chromanones 29 <00TL7129>. A novel one-pot synthesis of 3,5-disubstituted-2-pyrazolines 32 has been achieved with an unexpected coupling-isomerization sequence of haloarene 30, propargyl alcohol 31, and methylhydrazine <00ACIE1253>. 

Reactions Based on a Pd /Cu-catalyzed Coupling-Isomerization Process... 

Since the late 1990s, new multicomponent reactions based on a palladium/ copper-catalyzed coupling-isomerization sequence of 1-aryl prop-2-yn-l-ols and electron-deficient sp2-hybridized halogen compounds leading to the correspond-... 

The use of palladium-based chemistry continues to generate methods for heterocyclic synthesis. In a four-component reaction, ring-fused pyridines can be synthesized in one pot, referred to as a coupling-isomerization-enamine addition-cyclocondensation sequence (Scheme 106) <2005EJ01834>. 

Scheme 5.21 Propargyl activation and coupling-isomerization reaction as an entry to novel MCRs.

The CIR is exceptionally well suited as an entry to multi-component syntheses of aromatic heterocycles and on this basis Muller and coworkers [91f, 92] designed a coupling-isomerization-Stetter-Paal-Knorr sequence as a diversity-oriented approach to highly substituted furans and pyrroles (Scheme 5.22). 

Notes Value adjusted for coupled isomerization in water. 

Another option for Sonogashira coupling as an initiator of sequential catalysis is the coupling isomerization reaction (CIR) of electron-deficient halide and 1-aryl propargyl alcohols giving rise to the formation of chalcones [115, 116]. Based upon the CIR of electron-deficient halides 163 and l-(p-bromo phenyl) propyn-l-ol (164) Muller and Braun [117] presented a consecutive... 

Scheme 63 Sequential coupling-isomerization-Sonogashira coupling [117]...

Scheme 8 Propargyl activation by Sonogashira coupling of an electron-poor halide as an entry to coupling-isomerization (Cl) sequences...

Multicomponent Synthesis of Heterocycles by Coupling-Isomerization-Cyclocondensation Sequences... 

Muller TJJ, Ansorge M, Aktah D (2000) An unexpected coupling-isomerization. Sequence as an entry to novel three-component-pyrazoline syntheses. Angew Chem Int Ed 39 1253-1256... 

---