Scalable Rhodaelectro-Catalyzed Expedient Access to Seven-Membered Azepino[3,2,1- hi ]indoles via [5 + 2] C–H/N–H Annulation

Abstract

A rhodaelectro-catalyzed [5+2] N-H/C-H oxidative annulation of alkynes by 7-arylindoles has been accomplished, enabling the synthesis of seven-membered azepino[3,2,1-hi]indoles using electricity as the sole oxidant. The reaction can be scaled up to gram-scale by flow-electrocatalysis. Two key rhodium(III) intermediates were isolated and fully characterized. Cyclovoltammetric analysis, XPS studies and DFT calculations are suggestive of a rhodium(III-IV-II-III) manifold.

Review of electrochemical transition‐metal‐catalyzed C−H functionalization reactions

“…[26] Ackermann and his co-workers developed a method to synthesize a seven-membered azepino[3,2,1-hi]indoles from 7arylindoles by rhoda-electro-catalyzed [5 + 2] NÀ H/CÀ H oxidative annulation of alkynes using electricity as the oxidant (Scheme 20). [27] The reaction was carried out for different substituent at different position of the substrate. With the formyl group at the 3-position favored the reaction with an excellent yield, while other substitution patterns at C-3 proved less suitable.…”

Theoretical Study on the Rhodium-Catalyzed Electrochemical C–H Phosphorylation: Insights into the Effect of Electro-oxidation on the Reaction Mechanism

“…However, adding two molecules of Cu(OAc) 2 as the two-electron external oxidant could further facilitate reductive elimination, which can be regarded as equivalent to Rh(V). For Rh-catalyzed C−N bond formation upon reductive elimination, Ackermann and co-workers 49 demonstrated that electrochemical one-electron oxidation of Rh(III) to Rh(IV) could already inaugurate reductive elimination. The present catalytic reaction involves the formation of an even weaker C−P bond, which would require further oxidation of Rh(IV) to Rh(V) to gain more driving force for reductive elimination.…”

“…Recently, organic electrochemistry has attracted increasing attention due to its economical and environmentally benign reaction conditions, which involve the use of electricity instead of adding sacrificial oxidants or reductants to achieve target transformation. − Hitherto, the combination of electrochemistry and transition-metal catalysis has evolved into an appealing protocol in exploring oxidative C–H bond functionalization for achieving challenging transformations. − The pivotal electro-oxidation processes are presumed to oxidize the organometallic precursors to a higher oxidation state, allowing a more readily bond-forming reductive elimination. − Notably, a series of conversions regarding the electro-oxidation-driven Rh-catalyzed C–H functionalization have been successfully realized. − …”

Rh(iii)-catalyzed (5 + 2)-cycloaddition reactions of ortho-hydroxyethyl phenols with internal alkynes: efficient synthesis of benzoxepines

“…3,148.6,139.2,135.3,132.7,131.9,130.5,130.1,129.86,128.3,128.2,127.6,127.3,127.1,121.7,116.1,112.1,55.6. HRMS calcd (ESI) 2,3,oxepine (3ea). 4d,f Synthesized using the general procedure from 1e (21.4 mg, 0.1 mmol) and 2a (17.8 mg, 0.1 mmol).…”

“…1 However, there are only a limited number of reports on metal-catalyzed (4 + 3)-and (5 + 2)-cycloaddition reactions for the construction of seven-membered heterocyclic and carbocyclic scaffolds. 2 The benzoxepine is a very important seven-membered structural motif as it constitutes the main building block of several pharmaceutically important compounds and bioactive natural products (Fig. 1).…”