Green oxidation of indoles using halide catalysis

Abstract

Oxidation of indoles is a fundamental organic transformation to deliver a variety of synthetically and pharmaceutically valuable nitrogen-containing compounds. Prior methods require the use of either organic oxidants (meta-chloroperoxybenzoic acid, N-bromosuccinimide, t-BuOCl) or stoichiometric toxic transition metals [Pb(OAc)4, OsO4, CrO3], which produced oxidant-derived by-products that are harmful to human health, pollute the environment and entail immediate purification. A general catalysis protocol using safer oxidants (H2O2, oxone, O2) is highly desirable. Herein, we report a unified, efficient halide catalysis for three oxidation reactions of indoles using oxone as the terminal oxidant, namely oxidative rearrangement of tetrahydro-β-carbolines, indole oxidation to 2-oxindoles, and Witkop oxidation. This halide catalysis protocol represents a general, green oxidation method and is expected to be used widely due to several advantageous aspects including waste prevention, less hazardous chemical synthesis, and sustainable halide catalysis.

Catalytic Enantioselective Synthesis of Spirooxindoles by Oxidative Rearrangement of Indoles

“…Recently, Tong and co‐workers reported an elegant green protocol with in situ generated Br + as oxidant (Scheme 1 a). [8] We hypothesized that catalytic asymmetric halogenation in the indole 3‐position might lead to an enantioenriched 3‐halo indolenine intermediate. The good leaving ability of halide should allow the subsequent stereospecific rearrangement to take place under mild conditions (Scheme 1 c).…”

Ring-fused dimethoxybenzimidazole-benzimidazolequinone (DMBBQ): tunable halogenation and quinone formation using NaX/Oxone

“…The halide with Oxone gives oxidative transformations with an accompanying halogenation of naphthols and phenols, 11 and with and without halogenation for indoles. 12,13 Other metal-free oxidations, such as N-bromosuccinimde (NBS) with a small amount of H 2 SO 4 , 14,15 and PhI(OCOCF 3 ) 2 (PIFA), 8,16,17 are reported to induce conversion of p-dimethoxybenzenes to p-quinones without halogenation. The disadvantage of using NBS and PIFA is the generation of organic waste products.…”

Efficient Access to Aliphatic Esters by Photocatalyzed Alkoxycarbonylation of Alkenes

“…Furoindoline moiety is broadly found in the core structure of biologically active compounds and natural products. [35][36][37][38][39][40][41][42] Considering that oxindole-3-acetates are versatile building blocks for constructing heterocycle-fused indolines, 43,44 we decided to apply the above method to the preparation of furoindoline derivatives. As shown in Table 3, by treatment of N-arylacrylamides 7 and ethyl chlorooxoacetate 2a under the optimal conditions, followed by reduction with LiAlH 4 at 0 o C, furoindolines 9 were obtained as expected with excellent diastereoselectivities.…”

“…As shown in Table 3, by treatment of N-arylacrylamides 7 and ethyl chlorooxoacetate 2a under the optimal conditions, followed by reduction with LiAlH 4 at 0 o C, furoindolines 9 were obtained as expected with excellent diastereoselectivities. 43 This route was highly e cient, and a range of furoindoline derivatives was readily produced in only two steps from simple precursors. Additionally, N-(4methoxyphenyl)-N-methylmethacrylamide reacted with ethyl chlorooxoacetate 2a under the standard conditions, giving rise to the desired tricyclic furoindoline 9m, which could be readily converted into bioactive alkaloid physovenine in two steps.…”