Transition Metal-Free, Methoxide-Catalyzed Synthesis of Pyridoindolones

Abstract

A simple transition metal-free strategy for the synthesis of pyrido[1,2-a]indolone derivatives has been devised through sodium methoxide-catalyzed intramolecular cyclization of 2-alkenylated N-pyrimidyl indoles. The reactions involved a Smiles rearrangement/cyclization cascade, which resulted in a new series of N-fused indoles, potentially applicable skeletons in medicinal chemistry. This reaction presents simple eco-friendly reaction conditions, a high atom-and cost-economy, a short reaction time, and a broad range of substrate scope with high reaction efficiency.

Rhodium(iii)-catalyzed regioselective C2-alkenylation of indoles with CF3-imidoyl sulfoxonium ylides to give multi-functionalized enamines using a migratable directing group

“…Indole E underwent imine-enamine tautomerization to give the 2-enaminylated indole product E 0 . Finally, in the presence a base, the intramolecular nucleophilic aromatic substitution (SNAr) of compound E 0 occurred to deliver the desired enamine product 3 through a spiro-ring intermediate F. 4,5,16,18 The 1,5-pyrimidyl migration process in this reaction was further verified by the results of Scheme S1e (ESI †).…”

“…Also, the compound 3f′ could be readily transformed into product 3f with the promotion of strong base NaOEt, which was consistent with the results of the precedent literature (Scheme S1e, ESI†). 16 Finally, radical-trapping experiments were implemented by adding 2.0 equiv. of radical scavenger TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) and BHT (2,4-di- tert -butyl-4-methylphenol) and the reaction yields were not significantly affected.…”

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

“…Dihydropyrido [1,2-a]indolone (DHPI) skeletons are commonly found in natural products and pharmaceutical compounds (Figure 1) [1][2][3], which exhibit a wide range of biological and pharmaceutical activities [4]. For example, mersicarpine has been found to inhibit protein translation and induce apoptosis [5] and vinburnine acts as a vasodilator for the treatment of cerebrovascular insufficiency [6,7].…”

Facile synthesis of the spiro-pyridoindolone scaffoldviaa gold-catalysed intramolecular alkynol cyclisation/hydroindolylation

“…E-mail: vr.chepuri@ncl.res.in b lysts like Pd, Rh, Cu, Zn and Ir, as well as metal-free approaches, have been documented in the context of the synthesis of the pyridoindolone core. [13][14][15][16][17][18][19][20] However, as shown in Scheme 1, the product that results in the present cases has the potential for further nucleophilic additions that can be modulated for the synthesis of advanced intermediates documented in the total synthesis of this class of natural products. 21 For example, a simple addition of the ethyl anion at this spirocenter should deliver the known key intermediate employed in the mersicarpine synthesis and, importantly, in a short and convergent manner.…”