Phenols SNAr reaction

SNAr reactions also provide an important strategy for the preparation of various kinds of diaryl ethers. p-Dinitrobenzene reacts with even sterically hindered phenols to give the corre-... 

Sawyer and coworkers have developed an efficient alternative Ullmann synthesis of diaryl ethers, diaryl thioethers, and diarylamines using the SNAr reaction. Phenol, thiophenol, or aniline reacts with an appropriate aryl halide, in the presence of KF-alumina and 18-crown-6 in acetonitrile or DMSO to give the corresponding diaryl ether or diaryl thioether as shown in Eqs. 9.6 and 9.7.9a... 

Boger and co-workers used the intramolecular SNAr reaction on o-fluoronitro substrate 24 with NaH to prepare 25. Compound 25 was then converted in three steps into phenol 26, the cycloisodityrosine subunit of deoxybouvardin (2) and RA-VII (3) (Scheme 7). 24,25 Small amounts of the C9 epimer were also detected in the cyclization reaction, and when K2C03 was employed as the base, this epimer was formed nearly exclusively. 25 ... 

The optically pure bis-naphthalene ortho-methoxy amide 117 cyclized to the l,4-diazepin-5-one 118 in 86% yield and with >95% ee upon refluxing in ethylenediamine for 5 h to provide the first axially chiral 1,4-diazepine derivative (Scheme 64) <2000SL1616>. This example of a type g ring closure in which the leaving group is MeOH, proceeded in lower yield with an ot/ o-hydroxy substituent, with product distribution largely redirected toward an imidazolidine derivative in which the ethylenediamine reacted solely with the ester. In the structurally simpler salicylic acid ester series, activation of the phenol as the trifluoromethanesulfonate facilitated the SnAr reaction <1995TL7595>. 

Anilines (23 R = 2-Pr, PhCPfc X = Cl, Br, I) have been obtained in high yields (40-95%) from the reaction of the primary amines 2-propylamine and benzylamine with the ethers (24 R = Me, CH2=CHCH2, CH2-oxirane) in EtOH at room temperature.127 With secondary amines dealkylation of the aromatic ether to the corresponding phenol took place rather than SNAr dealkoxylation. 

In addition to the ruthenium SNAr chemistry discussed in Section 11.7.2, an analogous copper-assisted S Ar cyclization reaction of a boronic acid and a phenol has been reported to construct biaryl ethers 146 (Scheme 11.19). Specifically, this functionality was then incorporated into MMP inhibitors. The mild conditions were shown to tolerate amides and esters in the substrate, although the presence of an additional phenol resulted in only trace product. Some other transformations involving copper mediation are presented in Section 11.8. 

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