Iron‐Catalyzed Regioselective Hydroaryloxylation of CC Triple Bonds: An Efficient Synthesis of 2H‐1‐Benzopyran Derivatives

Abstract

An efficient, regioselective, iron-catalyzed intramolecular hydroaryloxylation of 2-propargylphenols or naphthols is reported. The reactions proceed through an endo-dig cyclization to afford benzopyran or naphthopyran derivatives in good to high yields using ironA C H T U N G T R E N N U N G (III) chloride as the catalyst with the assistance of aniline in dimethylformamide (DMF).Keywords: benzopyrans; hydroaryloxylation; iron catalysis; naphthopyrans; regioselective cyclizationThe transition metal-catalyzed or -mediated intramolecular O À H addition across unsaturated C À C bonds represents one of the most effective and atom-economical routes to oxygen-containing heterocycles. [1] These catalysts include lanthanide, [1a-c] Pt, [1d,i] Ru, [1p] Au, [1d,g,m,r] Ag, [1k,n] Cu [1e] etc. Oxygen-containing heterocyclic moieties such as benzopyran rings represent key structural units of a variety of natural compounds with interesting biological activities.[2] Different synthetic approaches to these compounds were reported in the literature, such as metal-catalyzed intramolecular ring closure, [1,3] acid-mediated condensation [4] and others.[5] Due to the drawbacks of the reported methods, for example, low yields, requirement of a large excess amount of one of the reagents or high catalyst costs, the development of sustainable, environmentally friendly and less expensive catalysts to accomplish the carbon-heteroatom bond forming process is highly desired. As a result, iron-catalyzed C À C and C À X bond formation has attracted considerable attention, because iron compounds are usually less toxic, low priced and easy to synthesize. There have been a lot of reports concerning the Fe-catalyzed C À C forming reactions with the assistance of Grignard reagents. [6,7] In the past few years, Fe-catalyzed C À C and C À X bond forming reactions without the utilization of Grignard reagents have also appeared. [8,9] In the course of our ongoing study on the development of new, transition metal-catalyzed, selective heterocycle forming protocols, [10] we found that iron-catalyzed benzopyran ring formation was accomplished with high regioselectivity with the assistance of amines. Herein we would like to present our results of the iron-catalyzed regioselective synthesis of 2H-1-benzopyran derivatives by the intramolecular hydroaryloxylation of C C triple bonds.For intramolecular 2-propargylphenol hydro-A C H T U N G T R E N N U N G aryloxyA C H T U N G T R E N N U N G lations, there exist two possible pathways, namely exo-dig or endo-dig cyclization to five-or sixmembered rings according to Baldwins rules [11] (Scheme 1). Generally, metal-mediated hydroaryloxylation facilitates an exo-attack to give five-membered rings [1a-e,12] there is only one example of the six-membered ring formation catalyzed by Ru.[1p] It is therefore attractive to develop a metal-catalyzed, regioselective hydroaryloxylation for six-membered ring formation.Scheme 1.

Iron Catalysis in Organic Synthesis

“…853 Thus, they synthesized a variety of benzo-and naphthopyrans in good yields and with high regioselectivity compared to the furan derivatives.…”

Iron‐Catalysed Hydrofunctionalisation of Alkenes and Alkynes

“…An iron-catalysed process was developed by Li for complementary 6-endo-dig cyclisation to give benzo-and naphthopyran derivatives 27 (Scheme 10). [28] FeCl 3 alone gave only low yields of naphthopyran product 27; however, good to excellent yields were obtained in the presence of aniline (0.2-2 equiv.). The addition of sodium carbonate or n-butylamine reversed the selectivity to give naphthofuran derivatives 26.…”

Access to 2,3‐Disubstituted Benzofurans through One‐Pot Acid‐Catalyzed Nucleophilic Substitution/TBAF‐Mediated Oxacycloisomerization

“…Tian et al have demonstrated a single example of the one‐pot synthesis of benzofuran from 2‐(1,3‐diphenylprop‐2‐yn‐1‐yl)phenol using ZnCl 2 (10 mol‐%) and TMSCl (50 mol‐%) at 70 °C in dichloroethane 10. Xiaobing Xu et al have observed the formation of benzofurans/naphthofurans under the action of 10 mol‐% FeCl 3 and Na 2 CO 3 at 135 °C, in their study 11. However, all these reactions require metal catalysts and, furthermore, they do not easily allow the generation of diversely substituted benzofurans.…”

“…[10] Xiaobing Xu et al have observed the formation of benzofurans/naphthofurans under the action of 10 mol-% FeCl 3 and Na 2 CO 3 at 135°C, in their study. [11] However, all these reactions require metal catalysts and, furthermore, they do not easily allow the generation of diversely substituted benzofurans. Herein, we describe a mild and general protocol for the synthesis of diversely 2,3-disubstituted benzofurans through a one-pot reaction under metal-free conditions.…”