Synthesis of Dibenzofurans Directly from Aryl Halides and ortho-Bromophenols via One-Pot Consecutive SNAr and Intramolecular Palladium-Catalyzed Aryl-Aryl Coupling Reactions

Abstract

Tandem reactions involve a sequence of reactions performed in the same reaction vessel.1) Nowadays, tandem reactions have emerged as powerful tools to meet the demands of modern organic chemistry due to the synthetic efficiency, molecular diversity, and low production costs, etc.2-5) Recently, we discovered tandem sequences for the efficient synthesis of diaryl ethers from arylmethanesulfonates and aryl halides.6) Meanwhile, it is well-known that dibenzofurans are good candidates for the study of molecular recognition, [7][8][9] catalytic reactions [10][11][12] and the geometry of metal-binding sites.13) Although Ames et al. had reported the synthesis of dibenzofurans, step-wise procedures were needed and the corresponding yields were also not good 14) ; lately, Liu et al. discovered that the dibenzofurans could be prepared by the reaction of ortho-iodophenols with silylaryl triflates in the presence of CsF and palladium, but expensive and excess base and not easily available starting material were used. 15)Thereby, the construction of dibenzofurans with simple, cheap and easily available organic molecules and base in a facile and efficient one-pot reaction is highly desirable. In the continuation of our program aimed at the discovery and development of new tandem reactions, 6) herein we report the synthesis of dibenzofurans directly from aryl halides with ortho-bromophenols via one-pot C(sp 2 )-O bond formation reaction (SNAr) in the presence of anhydrous K 2 CO 3 , followed by C(sp 2 )-C(sp 2 ) bond formation reaction (intramolecular aryl-aryl coupling reaction) catalyzed by Pd(OAc) 2 (Chart 1). Results and DiscussionDibenzofurans were efficiently and conveniently prepared via one-pot C(sp 2 )-O bond formation reaction (SNAr), followed by C(sp 2 )-C(sp 2 ) bond formation reaction (intramolecular palladium-catalyzed aryl-aryl coupling reaction) between aryl halides and ortho-bromophenols. As shown in Table 1, the dibenzofurans (3a-j) were obtained in 32-99% isolated yields. Take entry 1 (Table 1) for example, the mixture of 2-bromophenol (0.5 mmol), 4-fluoronitrobenzene (0.5 mmol), and anhydrous K 2 CO 3 (1.0 mmol) in DMF (3 ml) was stirred at 90°C under an argon atmosphere. When the starting materials were nearly consumed after 0.75 h according to thin-layer chromatography (TLC) analysis, Pd(OAc) 2 (0.025 mmol) and PPh 3 (0.05 mmol) were added to the above mixture, which was continued to be stirred at 90°C for 0.5 h under an argon atmosphere to give 2-nitrodibenzofuran (3a) in a 97% yield.It was found that the steric effects between 4-fluoronitrobenzene and 2-fluoronitrobenzene was obvious. For example, when 4-fluoro-or 2-fluoronitrobenzene was reacted with ortho-bromophenols, 2-nitrodibenzofuran (3a) and 4-nitrodibenzofuran (3b) were obtained in 97% for 1.25 h and 85% for 3.5 h yields, respectively (entries 1 vs. 2); 7-fluoro-2-nitrodibenzofuran (3e) and 7-fluoro-4-nitrodibenzofuran (3f) were obtained in 79% for 1 h and 64% for 6 h yields, respectively (entries 5 vs. 6); 8-methoxy-2-nitrodibenzofuran (3i) and...

Recent advances in the synthesis of dibenzofurans

“…Xu and Fan realized the synthesis of dibenzofurans from aryl halides and ortho -bromophenols by first creating a C–O bond by S N Ar followed by an intramolecular cyclization giving access to the dibenzofuran skeleton (Scheme 23). 58 The S N Ar reaction creating the C–O bond of ortho -bromodiarylether intermediates occurred in a short reaction time of 0.75 h in hot DMF. Then Pd(OAc) 2 and PPh 3 were added to the crude mixture, and the solution was heated various times depending on the substrates.…”

A One-Pot Synthesis of Dibenzofurans from 6-Diazo-2-cyclohexenones

“…To date, an array of approaches have emerged for the synthesis of the dibenzofuran motifs, which can be divided into two main categories (Scheme ). First, cyclization of unsubstituted (X = H) or 2-substituted phenoxybenzenes (X = halogen, CO 2 H, BF 3 K, OTs, N 2 + ) − was used to assemble the dibenzofuran framework through the formation of a C–C bond in the presence of a Cu, Ag, Pd, or Rh catalyst (eq 1). Second, Pd- or Cu-catalyzed intramolecular O-arylation of 2-arylphenols or 2-(2′-haloaryl)­phenols opened up a new path to dibenzofurans (eq 2).…”