Rhodium‐Catalyzed Copper‐Assisted Intermolecular Domino C−H Annulation of 1,3‐Diynes with Picolinamides: Access to Pentacyclic π‐Extended Systems

• Published in: Chemistry : a European journal 2019-04, Vol.25 (22), p.5733-5742
• Main Authors: Martínez, Ángel Manu, Alonso, Inés, Rodríguez, Nuria, Gómez Arrayás, Ramón, Carretero, Juan C.
• Format: Article
• Language: English
• Subjects: Activation; Alkynes; annulation; Chemical reactions; Chemistry; Copper; Copper compounds; fused-ring systems; Hydrogen bonds; Insertion; Intermediates; nitrogen heterocycles; Organic chemistry; reaction mechanisms; Regioselectivity; Rhodium; Substrates
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201900162

A new mode of reactivity of 1,3‐diynes in rhodium‐catalyzed oxidative annulation reactions has enabled the rapid assembly of extended π systems from readily available picolinamide derivatives. The process involves a double C−H bond activation and the iterative annulation of two 1,3‐diyne units, with each alkyne moiety engaged in an orchestrated insertion sequence with high regiocontrol, leading to the formation of five new C−C bonds and the construction of four fused rings in a single operation. Either isoquinoline‐1‐carboxamides or fused polycyclic systems can be accessed by a switch in the regioselectivity of the second diyne insertion depending on the reaction conditions. DFT theoretical calculations have elucidated that the cooperative participation of both rhodium and copper in substrate activation, favored in the presence of excess of the copper(II) salt, is key to such a reversal of regioselectivity and subsequent multiple cyclization leading to fused polycyclic products. The role of copper was found to be essential in assisting both multiple insertion and rhodium‐walking sequences, with the implication of intermediates with a Rh−Cu bond (2.60 Å). Rh‐catalyzed ring fusion: A rhodium‐catalyzed copper‐assisted method for the intermolecular annulation of picolinamides with two diaryl‐1,3‐diyne molecules is described. The four alkyne units participate in an orchestrated sequence of insertions and annulations, thereby enabling the assembly of up to four fused rings in a single step through double C−H bond activation and the construction of five C−C bonds (see scheme).