Antimycobacterial Benzofuro[3,2-f]chromenes from a 5-Bromochromen-6-ol

Abstract

A n t i m y c o b a c t e r i a l B e n z o f u r o [ 3 , 2 -f ] c h r o m e n e s f r o m a 5 -B r o m o c h r o m e n -6 -o l Abstract:In the course of our work on the synthesis of analogues of the specific antimycobacterial 3,3-dimethyl-3H-benzofuro[3,2-f]chromene, we prepared the previously unreported 5-bromo-2,2-dimethyl-2H-chromen-6-ol. We wish to report here an original synthetic scheme using this compound. The preparation of various 5-bromo-2,2-dimethyl-6-(aryloxy)-2H-chromenes was first investigated. This was followed by a palladium-catalysed cyclisation reaction, which takes place only in the presence of air, and leads to 3,3-dimethyl-3H-benzofuro[3,2-f]chromenes or 3,3-dimethyl-3H-4,7-dioxa-10-aza-benzo[c]fluorene. The antimycobacterial properties of these analogues have been investigated.

Access to Electron‐Rich Dibenzofurans through NBu4OAc‐Mediated Palladium Catalysis

“…[1][2][3] Consequently, synthetic routes toward dibenzofurans have garnered keen interest from synthetic chemists. [4][5][6][7][8][9][10][11][12][13][14][15][16] Retrosynthetic analysis of dibenzofuran reveals two separate intramolecular coupling strategies (Figure 1A): CÀ C bond formation through a diarylether 2 (Pathway A), or CÀ O bond formation through a biaryl motif 3 (Pathway B). Direct arylation has been applied successfully to form a decent range of dibenzofurans.…”

“…As such, the methodology can be less successful, depending on the electronic properties of the diarylether substituent. [4][5][6][7][8][9][10][11][12][13][14][15][16] That said, it should be noted that a number of mechanisms can be envisaged here, [20,21] most recently one which relies on the transmetalation step (rather than the CÀ H cleavage step) to determine regioselectivity. [22] Recently we reported a methodology on the synthesis of substituted dibenzofurans through a palladium-mediated intramolecular direct arylation of a diarylether utilising a quinoline ligand (Figure 1B).…”

“…The dibenzofuran framework 1 , and its analogues, represent a prominent class of natural products and biologically active entities [1–3] . Consequently, synthetic routes toward dibenzofurans have garnered keen interest from synthetic chemists [4–16] . Retrosynthetic analysis of dibenzofuran reveals two separate intramolecular coupling strategies (Figure 1A): C−C bond formation through a diarylether 2 (Pathway A), or C−O bond formation through a biaryl motif 3 (Pathway B).…”

“…This mechanistic pathway usually relies on the ‘acidity’ of the aryl C−H bond and thus, is less applicable to electron‐rich substrates. As such, the methodology can be less successful, depending on the electronic properties of the diarylether substituent [4–16] . That said, it should be noted that a number of mechanisms can be envisaged here, [20,21] most recently one which relies on the transmetalation step (rather than the C−H cleavage step) to determine regioselectivity [22] .…”

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

“…These compounds are presumably multitargeting drugs because of the diverse applications as insulin-like growth factor 1 receptor (IGF-1R) inhibitors [22], selective GSK-3β inhibitors important in Alzheimer's disease [23,24], and cyclin-dependent kinase (CDK) inhibitors [25][26][27]. Lastly, the aza analogue 9 of previously reported furo[3,2f]chromene 6 was examined for antimycobacterial activity [28]. This evidence encouraged us to investigate new methodologies for the synthesis of aza analogues of dibenzofuran from com-mercially available aminochloropyridines.…”