Macrocyclic diaryl ethers

Both TIN and TTA [Tl(OAc)3] have been known to act as electrophiles toward olefinic double bonds, enolizable ketones and nitrogen-containing compounds to afford a variety of natural products or their synthons. As already shown in Scheme 162, TIN was applied to phenolic oxidation by Yamamura and Nishiyama . In particular, this method which consists of TIN oxidation in MeOH followed by Zn reduction in AcOH is effective for the construction of macrocyclic diaryl ethers from the corresponding open-ring precusors, which are required to possess two o,o -dihalophenol moieties. 

Fourteen new macrocyclic diaryl ether heptanoids have been described (Table 4). The total syntheses of compounds 88, 89, 90, 91, 94 and 101 have also been reported (cf. Table 4). Based on synthetic and spectroscopic evidence, the structure of garuganin III has been revised to 101 [46]. 

Type I non-phenolic linear diarylheptanoids Type II phenolic linear diarylheptanoids Type III macrocyclic biarylheptanoids Type IV macrocyclic diaryl ether heptanoids Type V diarylheptanoids with cyclised C7-chain. 

Zhu et al. [103] reported a fadle access to biologically relevant macrocycles bearing an endo diaryl ether bond by means of a tandem Ugi-4CR/SNAr. The reaction between 3-hydroxyphenylacetic [or 3-(3-hydroxyphenyl)propionic] acid, aldehydes, amines, and isocyanide 197 gave the expected dipeptide derivatives 198 as a 1 1 mixture of diastereoisomers. The reaction gave high yields when performed in tri-... 

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