Aryne multicomponent reaction

An aryne multicomponent reaction involving isoquinoline and 5-bromo-1-methylisatin resulted in spirooxazino isoquinolines (Scheme 66).The reaction occurs with a number of iV-substituted isatins. Quinoline can replace the isoquinoline as well. Carbonyls other than the isatins can trap the anion as well. A variety of aromatic, aliphatic, and heteroaromatic aldehydes can function as the electrophile. When pyridine replaces isoquinoUne as the nucleophilic trap, the reaction forms an oxindole but not an oxazino pyridine derivative (14SL608). 

As the intermolecular multicomponent reactions, three-component cycloaddition reactions (21.2 [2+2-1-2] cycloaddition and 21.3 [3+2+1] cycloaddition) and two-component cycloaddition reactions (21.4 [4+2] cycloaddition) are described. As the intramolecnlar single-component reactions, cycloaromatization reactions (21.5 intramolecular hydroarylation of alkynes and cychzation via transition metal vinybdenes) are described. Aromatic ring constrnction reactions involving aryne reactions (Chapter 12), rearrangement reactions (Chapters 16 and 18), metathesis reactions (Chapter 17), and coupling reactions (Chapters 19 and 20) are described in these different chapters. 

A. Bhunia, A.T. Biju, Employing arynes in transition-metal-free, N-heterocycles initiated multicomponent reactions, Synlett 25 (2014)... 

X. Huang, T. Zhang, Multicomponent reactions of pyridines, a-bromo carbonyl compotmds and silylaryl triflates as aryne precursors a facile one-pot synthesis of pyrido[2,l-a]isoindoles. Tetrahedron Lett. 50 (2009) 208-211. 

F. Sha, X. Huang, A multicomponent reaction of arynes, isocyanides, and terminal alkynes highly chemo- and regioselective synthesis of polysubstituted pyridines and isoquinolines, Angew. Chem. Int. Ed. 48 (2009) 3458-3461. 

A. Bhunia, T. Roy, P. Pachfule, P.R. Rajamohanan, A.T. Biju, Transition-metal-free multicomponent reactions involving arynes, N-heterocy-cles, and isatins, Angew. Chem. Int. Ed. 52 (2013) 10040-10043. 

A. Bhunia, D. Porwal, R.G. Gormade, A.T. Biju, Multicomponent reactions involving arynes, quinolines, and aldehydes, Org. Lett. 15 (2013) 4620-4623. 

Additionally, functionalizations of C-H or N-H bonds to form carboxylic acids by reaction with CO2 were achieved using [(NHC)Cu] complexes. For example, Koboyashi has described a new access to isocoumarins by a multicomponent reaction that involves the coupling of an aryne, an alkyne and CO2 in the presence of a copper catalyst [eqn (11.2)]. ... 

The multicomponent reactions involving arynes as key intermediates have been studied as a method that offers direct, metal-free access to unusual heterocyclic scaffolds and 1,2-disubstituted arenes. ... 

This multicomponent reaction gives rise to a variety of ortho-functionalized arylamines 315 and thioethers 316 in good overall yields. The reaction can be extended to functionalized benzynes. Thus, the sulfonate 317 readily provides the expected aryne that adds regioselectively magnesium thiolate 318 providing the magnesium derivative 319. Its copper(I)-catalyzed trapping furnishes the tetrasub-stituted benzene 320 in 72% yield (Scheme 4.71) 171]. 

With co-presence of Arl, alkynes, TlOAc and (dba)2Pd in the reaction pot in which the aryne is generated, multicomponent coupling directed toward phenanthrenes is realized/ ... 

Multicomponent coupling reaction of arynes for construction of heterocyclic skeletons 12H(85)1333. 

Multicomponent coupling represents a synthetically attractive approach for the assembly of complex and diverse molecules by a cascade of elementary chemical reactions. Mulhcomponent couplings involving aryne components have recently attracted considerable attention due to the extraordinary reactivity of the aryne species. 

A three component coupling reaction involving carbopallada-tion of the aryne followed by a Fleck coupling with tert-butyl acrylate affords oFtAo-substituted cinnamic acids in good yields (eq 11). An ene reaction between the aryne, generated in THF at room temperature, and an alkyne creates allenylbenzenes in moderate yields. The reaction of jr-allylpalladium species with the benzyne created from 2-(trimethylsilyl)phenyl triflate provides access to several types of products in multicomponent... 

E. Yoshioka, S. Kohtani, H. Miyabe, A multicomponent coupling reaction induced by insertionof arynes into the C=0bond of formamide, Angew. Chem. Int. Ed. 50 (2011) 6638-6642. 

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