The Selective Cross-Coupling of Secondary Alkyl Zinc Reagents to Five-Membered-Ring Heterocycles Using Pd-PEPPSI-IHept super(Cl)

• Published in: Angewandte Chemie Vol. 127; no. 33; pp. 9638 - 9642
• Main Authors: Atwater, Bruce, Chandrasoma, Nalin, Mitchell, David, Rodriguez, Michael J, Pompeo, Matthew, Froese, Robert DJ, Organ, Michael G
• Format: Journal Article
• Language: English
• Published: 01.08.2015
• Subjects: Catalysis; Catalysts; Chemical reactions; Derivatives; Furans; Palladium; Selectivity; Zinc
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201503941

The ability to cross-couple secondary alkyl centers is fraught with a number of problems, including difficult reductive elimination, which often leads to beta -hydride elimination. Whereas catalysts have been reported that provide decent selectivity for the expected (non-rearranged) cross-coupled product with aryl or heteroaryl oxidative-addition partners, none have shown reliable selectivity with five-membered-ring heterocycles. In this report, a new, rationally designed catalyst, Pd-PEPPSI-IHept super(Cl), is demonstrated to be effective in selective cross-coupling reactions with secondary alkyl reagents across an impressive variety of furans, thiophenes, and benzo-fused derivatives (e.g., indoles, benzofurans), in most instances producing clean products with minimal, if any, migratory insertion for the first time.Original Abstract: Die Kreuzkupplung unterschiedlicher Fuenfring-Heterocyclen mit sekundaeren Alkylzinkreagentien wird durch den neuen Praekatalysator Pd-PEPPSI-IHept super(Cl) ermoglicht, der ein sterisch anspruchsvolles N-heterocyclisches Carben traegt. Der Katalysator verhindert migratorische Insertionsreaktionen (Umlagerungen), und die gewuenschten Produkte werden mit hoher Selektivitaet gebildet.