A Procedure for Transforming Indoles into Indolequinones

Abstract

A procedure that converts a series of structurally diverse, readily available indole derivatives to their corresponding indolequinones is described. The three-step route commences with an iridium catalyzed C-H borylation to give a 7-borylindole that upon oxidation-hydrolysis affords the 7-hydroxyindole. Subsequent oxidation provides the indolequinone.

Iridium‐Catalysed C−H Borylation of Heteroarenes: Balancing Steric and Electronic Regiocontrol

“…Owing to the prevalence of indole in pharmaceutical agents, the Ir-catalysed CÀH borylation of many substituted indole derivatives has been well documented and this discussion will focus on this, emphasising differences with the other heterocycles where relevant. [111][112][113][114][115][116][117][118] Bisborylation of indole affords the 2,7-disubstituted product 128, and other C-2 substituted indoles, such as 2-phenylindole, also undergo selective borylation at C-7. Significantly, reaction of 2phenylindole is selective for the fused arene ring, leaving the phenyl substituent intact (Scheme 15 c,d).…”

Acyl‐Directed ortho‐Borylation of Anilines and C7 Borylation of Indoles using just BBr3

“…However,5 -SMe,5 -NO 2 and 4-CN substituted indoles did not furnish isolable C-BPin products,while attempts with abulkier group at C6, 6-(p-tolyl)-N-pivaloyl-indole,led to C2 borylation dominating (35:65 C7:C2). Compounds 8x are useful in Suzuki-Miyaura cross couplings,a llylations and halogenations, [8] and we note that 8a readily undergoes oxidation with H 2 O 2 /NaOH to form 7-hydroxy-indole.…”

“…[5] To date the selective C5 À H/C7 À Hb orylation of indoles in the presence of C2 À H/ C3 À Hr equires prefunctionalised indoles (e.g.h alide at C5/ C7) or functionalisation of the more reactive C2ÀH/C3ÀH site prior to C5ÀH/C7ÀHb orylation and then unmasking of the C2 À H/C3 À H. [6] To the best of our knowledge,o ne example of directed iridium-catalysed C À Hb orylation [7] provides the only exception to these requirements (Scheme 1, middle left). [8] This process while notable uses ruthenium and iridium catalysts and substrates containing C6 substituents are not viable (6,7-disubstituted indoles are also bioactive motifs for example,i ndole isosteres of combrestatins). [5, 6c,9] Therefore as imple,p recious metal free route for the C À Hb orylation of indoles that is selective for:( i) C7 (over C2), including for C6 substituted indoles,a nd (ii)C5 (over C3), would be highly notable particularly if using areadily removed directing group.…”

Iridium-Catalyzed Triborylation of 3-Substituted Indoles

“…[9] Although a solitary example that results in a regioisomeric mixture, this observation indicates that the iridium-catalyzed borylation could potentially be used to selectively functionalize the indole heterocycle at sites in addition to C2, C3, and C7, further extending the utility of this reaction. In an extension of our ongoing interest in the iridium-catalyzed borylation of indoles, [10,11] we report herein that several 3-substituted indoles undergo a one-pot regioselective, iridiumcatalyzed triborylation at the C2, C5, and C7 sites, delivering tetrasubstituted indoles with a substitution pattern that is difficult to prepare using traditional methods.…”