O-Halophenol

A convenient preparation of dihydrobenzofurans has been achieved from the appropriately functionalized ort/ o-halophenol derivatives. Treatment of the aryl iodide (5)-33 with (TMS)3SiH and EtsB in the presence of air at room temperature, gave the aryl radical which cyclized in a 5-exo-trig mode and provided the bicyclic derivatives 34/35 as a 29 1 mixture of diastereoisomers in favour of 34 (Reaction 7.40) [51]. 

Benzofurans. 2-Substituted benzofurans can be obtained in 65-83% yield by reaction of o-iodophenols and 1-alkynes in the presence of Cu20 suspended in pyridine. This synthesis has been conducted in the past by reaction of copper(I) acety-lides with o-halophenols, but yields are somewhat lower. In addition, copper(I) acetylides can be explosive. 

Oxidative phenolic coupling.1 The vancomycin antibiotics are polypeptides with bridging diphenyl ether groups. Evans et al. have shown in model systems such as 1 that cyclization to o-halophenolic peptides (2) can be accomplished by oxidation with thallium(III) nitrate in THF-methanol or CH2Cl2-methanol followed by CrCl2 reduction of a para-quinol intermediate (a). In three cases the yield of cyclic products was 40-48%. 

Okuyama, M., and Ikawa, S.-I., Intramolecular hydrogen bond and molecular conformation. Part 3—effect of temperature and pressure on the IR spectra of o-halophenols in dilute solutions, J. Chem. Soc. Faraday Trans., 90, 3065-3069 (1994). 

Lin, T.-S., and Fishman, E., Enthalpies of intramolecular hydrogen bonds of o-halophenols and deuterated o-halophenols in the vapour phase, Spectrochim. Acta Part A, 23, 491-500 (1967). 

Dibenzo-1,4-dioxins are prepared from o-halophenols on treatment with Cu powder in the presence of K2CO3 or from 2-(2-hydroxyphenoxy)diazonium salts [126] ... 

The reaction of o-halophenols and terminal alkynes in the presence of Pd and/or Cu catalysts provides a very convenient, direct route to benzofurans (Eq.4). 

Recently, the sequential, one-pot Pd-catalyzed coupling of an o-halophenol and a terminal alkyne, followed by cross-coupling with a vinylic halide has provided an efficient approach to a complex benzofuran-containing natural product (Eq.6) [27]. 

The photochemical substitution reactions of 2-naphthoxide anion and o-halophenol (X = Br, I) in an aqueous sodium sulfite solution were also reported Photosubstitution of the sulfo group for hydrogen is observed under irradiation of sulfonated derivatives of hydroquinone. Benzo[a]phenanthridine-5-ones (156) (159) were synthesized by photo-induced substitution and cycloaddition of 3-chloroisoquinolin-l-ones... 

In 2010, Bao and Shen reported a novel and efficient procedure for the synthesis of benzoxazole and benzimidazole derivatives. The one-pot cascade process is based on Cul under ligand-free conditions. A variety of carbodiimides coupled with o-halophenols or o-haloanilines to give the products in moderate to excellent yields under the mild conditions (Scheme 2.134). 

This domino Sonogashira-cyclization strategy can also be applied to the synthesis of benzofurans. The use of o-halophenols, as opposed to anilines, and terminal alkynes results in 2-substituted benzofurans. Many research groups have reported the use of such a strategy, which incorporates both palladium and/or copper catalysis [166], An illustrative example is shown in Scheme 24.55. Bates et al. demonstrated that the combination of o-iodophenols and arylacetylenes using copper catalyst 88 led to the desired benzofuran products such as 89 in excellent yields [169]. 

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