A General Cp*Co^III‐Catalyzed Intramolecular C−H Activation Approach for the Efficient Total Syntheses of Aromathecin, Protoberberine, and Tylophora Alkaloids

Abstract

Herein,w er eport aC p*Co III -catalyzed CÀHa ctivation approach as the key step to create highly valuable isoquinolones and pyridones as building blocks that can readily be appliedi nt he total syntheses of av ariety of aromathecin, protoberberine, and tylophoraa lkaloids. This particular CÀHa ctivation/annulationr eaction was achieved with severalt erminal as well as internal alkyne coupling partners delivering ab road scope with excellent functional group tolerance. The synthetic applicability of this protocolr eportedh erein was demonstrated in the total syntheses of two To po-I-Inhibitors and two 8-oxyprotoberberine cores that can be further elaborated into the tetrahydroprotoberberinea nd the protoberberine alkaloid core. Moreover these building blocks were also transformed to six different tylophora alkaloids in expedient fashion.

Cp*CoIII‐Catalyzed Bis‐isoquinolone Synthesis by C−H Annulation of Arylamide with 1,3‐Diyne

“…Based on previous reports [6,11] ando ur preliminaryc ontrol experiments, [13] we propose the mechanisma st hat shown in Scheme5.C ationicc omplex A can undergo cyclometallation C followed by regioselective migratory insertion to provide Cobalt(III)alkenyl intermediate E,w hich may subsequently undergo reductive elimination.…”

“…[9] This is not only cost-effective, but also uniquei nt erms of its reactivity. [11] In our program focusingo nt he use of earth-abundant metalc atalysts for CÀH bond functionalizations, we envisioned the bis-annulation strategy for the synthesis of isoquinolones starting from benzamide and 1,3-diyne by employing Cp*Co III as the catalyst (Scheme 1c). Subsequently,J eganmohan and co-workersr eported the synthesis of isoquinolonesb y Cp*Co III catalysis through annulation of benzamides with alkynesu sing NÀOMe as an internal oxidant.…”

Comparison of the Reactivities and Selectivities of Group 9 [Cp*MIII] Catalysts in C−H Functionalization Reactions

“…Later,G lorius and co-workersi mproved this annulation reaction by using a [Cp*Co III ]c atalyst( Scheme8b). [17] Thus,t he use of [Cp*Co-(CO)I 2 ]i nt he presence of AgSbF 6 ,C sOPiv, and HOAc in TFE effectively furnished isoquinolones and pyridones. Interestingly, unlike the above-described rhodium catalysis, this reactionw as found to be facile for substrates that containedn ot only internal but also terminal alkynes, therebye nabling access to interesting natural products.…”

Developments in Cp*CoIII‐Catalyzed C−H Bond Functionalizations

“…In 2017, intramolecular version of isoquinolone synthesis was documented by Glorius and co‐workers with excellent regioselectivity under the Co(III)‐catalysis. (Scheme b) . The method was also applicable to the synthesis of pyridone derivatives employing acrylamide derivatives.…”