Synthesis of Thieno[3,2-b]indoles via Halogen Dance and Ligand-Controlled One-Pot Sequential Coupling Reaction

Abstract

A two-pot synthesis of thieno[3,2-b]indole from 2,5-dibromothiophene is described. A halogen dance of 2,5-dibromothiophene was performed with LDA, and subsequent Negishi coupling was performed with 2-iodoaniline derivatives to provide the corresponding coupling products. The resulting two bromo groups have different reactivities, which were utilized for the one-pot Suzuki-Miyaura coupling/intramolecular Buchwald-Hartwig amination to produce thieno[3,2-b]indole via an assisted tandem catalysis that involved in situ ligand exchange.

Magnesium Bisamide-Mediated Halogen Dance of Bromothiophenes

“…Despite this attractive synthetic potential, the scope of this substrate has not been investigated in detail probably because of difficulties in controlling the reactivity of the transient thienyllithium species. Recently, our research group published the first one-pot halogen dance/Negishi coupling for rapid access to multiple arylated thiophenes and furans in a regiocontrolled manner . During the course of the investigation, transmetalation of the transient organolithium species to organozinc species proved essential for smooth transformation.…”

Microflow Fluorinations of Benzynes: Efficient Synthesis of Fluoroaromatic Compounds

“…2-(Trimethylsilyl) phenyl trimethylsilyl ether 6a, which is a new benzyne precursor that was recently reported by our group, 95) was also successfully used in the benzyne fluorination reaction under microflow conditions using three syringes with two Comet X-01 micromixers, as shown in Chart 2. Hence, a solution of 6a (0.…”

Recent advances in the synthesis of thienoindole analogs and their diverse applications

“…Hayashi et al 34 reported the synthesis of thieno[3,2- b ]indole from 2,5 dibromothiophene 57 and lithium diisopropylamide (LDA), which resulted in the formation of transient thienyl anion species 58 via the mediated halogen dance reaction, 35 which led to the development of two chemical bonds in one pot, followed by Negishi coupling 36 and Suzuki–Miyaura coupling or Buchwald–Hartwig amination via tandem catalysis in the presence of 1,1′-bis(diphenylphosphino)ferrocene (dppf) and tri- tert -butylphosphine ( t Bu 3 P) ligand to give thieno[3,2- b ]indole.…”

“…The following sequential coupling reactions ( Scheme 34 ) were reported as tandem catalytic pathways. 34 …”

“…Hayashi et al 34 Convenient and cheap synthetic approaches are urgent to meet the growing demand of hetero-arylated thieno [3,2-b] indoles, which are widely used in optoelectronic material engineering. In this context, the retro-synthetic approach towards the synthesis of thienoindoles is shown in the following scheme (Scheme 35).…”