Indole‐ and Pyrrole‐BX: Bench‐Stable Hypervalent Iodine Reagents for Heterocycle Umpolung

Abstract

Abstract:The one-step synthesis of the bench-stable hypervalent iodine reagents IndoleBX and PyrroleBX using mild Lewis acid catalyzed conditions is reported. The new reagents are stable up to 150 °C and were applied in the C-H arylation of unactivated arenes using either rhodium or ruthenium catalysts. A broad range of heterocyclic systems of high interest for synthetic and medicinal chemistry was accessed in high yields. The developed C-H functionalization could not be achieved using reported reagents or methods, highlighting the unique reactivity of Indole-and Pyrrole-BX.Pyrrole and indole heterocycles are omnipresent in natural and synthetic biologically active compounds and have found countless applications in the pharmaceutical and agrochemical industries.[1]

Benziodoxole Triflate as a Versatile Reagent for Iodo(III)cyclization of Alkynes

“…The synthesis and reactivity of arylbenziodoxolones derived from 2‐iodobenzoic acid and arenes have been studied before . Recently, Waser has developed a synthetic method for heteroarylbenziodoxolones from indole and related electron‐rich heteroarenes, and demonstrated their utility in rhodium‐ or ruthenium‐catalyzed directed C−H heteroarylation reactions . On the other hand, (hetero)arylbenziodoxoles such as those reported here are unprecedented in the literature, and their reactivity remains elusive.…”

“…[19] Recently,W aser has developed as ynthetic method for heteroarylbenziodoxolones from indole and relatede lectron-rich heteroarenes, andd emonstrated their utility in rhodium-or ruthenium-catalyzed directed CÀHh eteroarylation reactions. [20,21] On the other hand, (hetero)arylbenziodoxoles such as those reported here are unprecedentedi nt he literature, and their reactivity remains elusive. To explore the potential utility of these compounds, we examined severalt ransformations involvingC -I III bond cleavage (Scheme 6).…”

Recent Advances in the Catalytic Functionalization of “Electrophilic” Indoles

“…Finally, efforts towards the realization of bench‐stable hypervalent iodine‐indole reagents 58 , featuring umpolung reactivity, were finally carried out by Waser and colleagues . In particular, the authors proposed a straightforward synthesis of C(3)‐indole carrying benziodoxole (BX) unit that proved to be stable up to 150 °C and found remarkable applications in the Rh or Ru‐catalyzed arylation of variously substituted arenes ( 59 ).…”

“…(Scheme a). The same team extended this methodology also to the selective Rh or Ir‐catalyzed C—H activation of formyl group of ortho ‐substituted benzaldehydes and consequent heteroarylation with indole‐BX reagents 58 [26d] . The methodology enabled the direct preparation of acylated indoles 62 in high yields that are not trivially achievable via classic Friedel‐Crafts acylation reactions (Scheme b).…”

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

“…Aryl iodonium salts have been used successfully in transition-metal-catalyzed transformations [ 22 ], but only one application of indole iodonium salts in copper catalysis by You and co-workers had been reported until 2017 [ 23 ]. In this context, indole-based benziodoxole hypervalent iodine reagents, recently introduced by Yoshikai's and our group [ 24 – 27 ], appeared ideal partners to develop a new C–H heteroarylation of pyridinones.…”