Exceptionally Mild Palladium(II)-Catalyzed Dehydrogenative C–H/C–H Arylation of Indolines at the C-7 Position under Air

Abstract

An improved method for the dehydrogenative C-H/C-H cross-coupling at the C-7 position of indolines containing a urea as a directing group is reported. The new protocol is a rare example of an aerobic palladium(II)-catalyzed cross dehydrogenative coupling (CDC) reaction that proceeds at low temperature. The use of either Cu(OAc)2 in an open flask or dioxygen (balloon) at 50 °C tolerates indolines not substituted at C-2 and C-3, thereby extending the scope of the previous method that suffers from indoline-to-indole oxidation.

Synthetic Applications of Oxidative Aromatic Coupling—From Biphenols to Nanographenes

“…Cross‐coupled products such as 125 – 127 were obtained in yields ranging from 31 % to 95 %. A closely related reaction, namely the palladium(II)‐catalyzed dehydrogenative coupling of arenes with indolines at C7, has also been reported (products 128 ; Figure ) …”

“…[116] Crosscoupled products such as 125-127 were obtained in yields ranging from 31 %to95%.Aclosely related reaction, namely the palladium(II)-catalyzed dehydrogenative coupling of arenes with indolines at C7, has also been reported (products 128;F igure 8). [117] Guan and co-workers showed that biaryls of type 129 can be synthesized by coupling tertiary benzamides with arenes by utilizing the in situ generated palladium(II) triflate as the catalyst and dipotassium peroxodisulfate as the oxidant (Figure 8). [118] Homo-and cross-dehydrogenative coupling reactions yielding biaryls were also reported by Zhang and Rao,w ho used HFIP as the solvent and sodium periodate/dipotassium peroxodisulfate as oxidants.…”

RhIII‐Catalyzed CF3‐Carbenoid C‐7 Functionalization of Indolines

“…Because of the significance of C‐7‐substituted indolines, the direct functionalization of the C–H bond at that position by using a transition‐metal‐catalyzed C–H activation strategy is highly desirable. Recently, several research groups have reported examples of transition‐metal‐catalyzed chelation‐assisted functionalizations at the C‐7 position of indolines by using various coupling partners in arylation, alkenylation, alkynylation,[5f], amination, acylation, allylation, thiolation, selenation, and alkylation reactions as well as the use of a C–H functionalization/annulation reaction sequence to build 1,7‐fused indolines . To the best of our knowledge, however, there is only one report of the direct metal‐catalyzed C‐7 functionalization of indolines by using diazo compounds, mainly diazomalonate derivatives, as cross‐coupling partners.…”

Regioselective C-H Functionalization of the Six-Membered Ring of the 6,5-Fused Heterocyclic Systems: An Overview

“…The selective functionalization at the C7 position of indoles is also very difficult to achieve and usually requires the substituents at the C2 in order to block this reactive position [83,84]. However, an efficient route including reduction of indoles to the corresponding indoline derivatives followed by C-H functionalization at the C7 position, then oxidation, successfully provided the expected C7-functionalized products (Scheme 23) [85][86][87][88][89][90]. However, the development of the appropriate methods allowing the direct C-H arylation of indoles at the C7 position without additional steps of reduction and oxidation is highly needed.…”