A Multicomponent Reaction of Arynes, Isocyanides, and Terminal Alkynes: Highly Chemo‐ and Regioselective Synthesis of Polysubstituted Pyridines and Isoquinolines

Abstract

Many components make light work: A novel synthetic strategy for the preparation of pyridines and isoquinolines in high chemo- and regioselectivity has been developed. By manipulating the reaction conditions, either product can be generated smoothly in a highly efficient and atom-economic manner (see scheme).

4.09 Nucleophilic Coupling with Arynes

“…229 Similar reactions using N-heteroaromatics (pyridine and isoquinoline) 230 cyclic ethers [232][233][234] as nucleophiles also readily occur in the presence of such protic electrophiles as nitriles, ketones, terminal alkynes, and chloroform (Scheme 78).…”

Sustainable Chemistry Metrics

“…[63] MCR reactions are powerful synthetic tools that have been extensively applied in combinatorial chemistry to prepare libraries of chemical compounds. Despite their long history, MCRs continue to attract the attention of synthetic chemists for the development of new reactions [64] and strategies [65] towards new families of compounds. MCRs satisfy many of the principles of Green Chemistry.…”

Transition-Metal-Free Synthesis of Benzo-Fused Five- and Six-Membered Heterocycles Employing Arynes

“…Recently, Sha and Huang reported a unique MCR involving arynes, isocyanides, and terminal alkynes, which resulted in a direct access to isoquinolines 88 or polysubstituted pyridines 89 with excellent selectivity [69]. Notably, the combination of four molecules took place in a highly efficient, selective, and atom-economic manner.…”

“…Synthesis of isoquinoline derivatives using aryne MCRs [69]. SCHEME 45 Synthesis of pyridine derivatives using aryne MCRs [69].…”

“…Mechanism of the formation of isoquinolines and polysubstituted pyridines [69]. SCHEME 47 Synthesis of disubstituted pyridine derivatives using aryne MCRs [70].…”