Rational Development of Remote C−H Functionalization of Biphenyl: Experimental and Computational Studies

A simple and efficient nitrile‐directed meta‐C−H olefination, acetoxylation, and iodination of biaryl compounds is reported. Compared to the previous approach of installing a complex U‐shaped template to achieve a molecular U‐turn and assemble the large‐sized cyclophane transition state for the remo...

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Veröffentlicht in:Angewandte Chemie 2020-03, Vol.132 (12), p.4800-4807
Hauptverfasser: Fan, Zhoulong, Bay, Katherine L., Chen, Xiangyang, Zhuang, Zhe, Park, Han Seul, Yeung, Kap‐Sun, Houk, K. N., Yu, Jin‐Quan
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Sprache:eng
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Zusammenfassung:A simple and efficient nitrile‐directed meta‐C−H olefination, acetoxylation, and iodination of biaryl compounds is reported. Compared to the previous approach of installing a complex U‐shaped template to achieve a molecular U‐turn and assemble the large‐sized cyclophane transition state for the remote C−H activation, a synthetically useful phenyl nitrile functional group could also direct remote meta‐C−H activation. This reaction provides a useful method for the modification of biaryl compounds because the nitrile group can be readily converted to amines, acids, amides, or other heterocycles. Notably, the remote meta‐selectivity of biphenylnitriles could not be expected from previous results with a macrocyclophane nitrile template. DFT computational studies show that a ligand‐containing Pd–Ag heterodimeric transition state (TS) favors the desired remote meta‐selectivity. Control experiments demonstrate the directing effect of the nitrile group and exclude the possibility of non‐directed meta‐C−H activation. Substituted 2‐pyridone ligands were found to be key in assisting the cleavage of the meta‐C−H bond in the concerted metalation–deprotonation (CMD) process. Ferngesteuert: Eine Nitril‐dirigierte meta‐C‐H‐Funktionalisierung von Biphenylderivaten wurde durch die Verwendung von 2‐Pyridon als Ligand realisiert. DFT‐Rechnungen zeigen, dass ein neuartiger, ligandhaltiger Pd‐Ag‐ Übergangszustand für die meta‐Selektivität verantwortlich ist.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201915624