Arylation of Phenols, Alcohols, and Thiols

Ring arylation of phenols with aryl halides to produce arylphenols is competitive with aryl ether formation. As discussed in Chapter 3.3.2, it is known that the ring arylation proceeds with Pd(0)-PPh3 catalyst. 

Efficient formation of aryl t-butyl ethers from electron-rich chlorides or bromides can be carried out using biphenyl-type monophosphines (IV-1, IV-4, IV-12) [5]. The aryl r-butyl ether 12 was prepared from electron-rich m-chloroanisole (11) using IV-4 as a ligand. The t-butyldimethylsilyl ether 13 was obtained from the electron-deficient bromides 5 using DPPF (XI-1) [1], Also t-butyl ether formation is carried out by using P(t-Bu)3. 

The aryl r-butyl ether 15 and silyl ether 18, prepared by the Pd-catalyzed reaction, can be converted easily to phenols 16, and these reactions offer convenient synthetic methods for phenols 16 from aryl halides 14 and 17. Based on this reaction, the first synthesis of 4-chlorobenzofiiran (18c), which is difficult to synthesize by conventional methods, was carried out. Selective mono-r-butoxylation of 2,6-dichloroacetaldehyde dimethylacetal (18a) using P(r-Bu)3 as a ligand gave the r-butyl ether 18b, and subsequent treatment with aq. HCl afforded 4-chlorobenzofuran (18c) in 51 % overall yield. Further conversion of 18c to various 4-substituted benzofurans is possible by Pd-catalyzed substitutions of the 4-chloro group in 18c [6]. 

Strongly electron-deficient aryl halides react with alcohols without any catalyst. Catalyzed reaction is sometimes better than uncatalyzed reaction as shown by the reaction of 4-bromo-2-chlorobenzonitrile (25) with cyclohexanol. The ether 26 was obtained in 80 % yield using Pd(0)-VI-9 as a catalyst. On the other hand, the uncatalyzed reaction gave equal amounts of 26 and 27 [7]. 

Preparation of cyclic ethers by intramolecular reactions of the primary (29 and 33) and the secondary alcohols (31 and 35) proceeds more easily using CS2CO3 or K3PO4, and binaphthyl-based monophosphine ligands VI-1, VI-9 [9], The five-, six-, and seven-membered cyclic ethers 30, 32, and 34 were prepared from the aryl chloride 31 and bromides 29 and 33. The benzoxazapine 36 was obtained without racemization of chiral alcohol by the cyclization of the optically active bromo alcohol 35. 

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