An Ir(iii)-catalyzed aryl C–H bond carbenoid functionalization cascade: access to 1,3-dihydroindol-2-ones

Abstract

An Ir(iii)-catalyzed relay aryl C-H bond carbenoid insertion cascade of N-aryl-2-pyridinamines with diazo Meldrum's acid has been developed. This method provides an efficient approach to multifunctionalized 1,3-dihydroindol-2-ones with a broad range of functional group tolerance. Furthermore, this protocol could be applied for the concise synthesis of bioactive hematopoietic growth factor analogues.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…Scheme 147A ), 873 – 875 , 884 while the use of Meldrum's acid furnishes 1,3-dihydroindol-2-ones, although the product obtained strongly depends on the substitution pattern on the DG or the aryl ring ( Scheme 147K ). 885 2,3-Diarylated indoles can be obtained by reaction with alkynes, of which Kantam recently reported a heterogeneous version using Pd supported on nanocrystalline Mg oxide [NAP–Mg–Pd(0)] ( Scheme 147L ). 886 This heterogeneous catalyst could be recycled and reused for at least 4 runs without considerable changes in yields.…”

Rh(III)‐Catalyzed Csp2−Csp3 Bond Cleavage/Carbonylethylation of α‐Indolyl Alcohols

“…General procedure for the synthesis of arylalkylketone S3 : Indole (3.0 mmol) was coupled with 2‐bromopyridine (569 mg, 3.6 mmol) using K 3 PO 4 ⋅ 3H 2 O (1.68 g, 6.3 mmol), CuI (29 mg, 1.5 mmol), and N , N ‐dimethylcyclohexane‐1,2‐diamine (85 mg, 6.0 mmol). Flash chromatography on silica gel (petroleum ether: ethyl acetate=20:1) provided of the desired product S3 [13,23] …”

Diazo Compounds: Versatile Synthons for the Synthesis of Nitrogen Heterocycles via Transition Metal‐Catalyzed Cascade C–H Activation/Carbene Insertion/Annulation Reactions

“…[24] Ther eactiono fN-(para-substituted aryl)-2-pyridinamines provided double C-H functionalization products.H owever, those arylamines 35 having large steric hindrance produced only the mono-selective C-H carbenoid functionalization products 36.T he target product N-(2-pyridyl)-2,3-dihydroindol-2-one 36 could be converted to bioactive molecule analogues,s uch as the hematopoietic growth factor analogue 38 (Scheme 18). [24] Ther eactiono fN-(para-substituted aryl)-2-pyridinamines provided double C-H functionalization products.H owever, those arylamines 35 having large steric hindrance produced only the mono-selective C-H carbenoid functionalization products 36.T he target product N-(2-pyridyl)-2,3-dihydroindol-2-one 36 could be converted to bioactive molecule analogues,s uch as the hematopoietic growth factor analogue 38 (Scheme 18).…”

“…Iridium-catalyzed C-H activation of acetanilides to oxindoles. [24] Scheme17. Thesynthesis of isoindigo.…”

“…In 2017, Zeng and co‐workers developed an Ir‐catalyzed C−H bond carbenoid functionalization of N ‐aryl‐2‐pyridinamines 35 with diazo‐Meldrum's acid to provide 1,3‐dihydroindol‐2‐ones 36 (Scheme ) . The reaction of N ‐( para ‐substituted aryl)‐2‐pyridinamines provided double C–H functionalization products.…”