Oxidative cyclization, phenol ethers

In this route a dihydroisoquinoline (58) is N alkylated with a highly functionalized o -bromoacetophenone (59) to give a quaternary salt (60), which is treated with base and cyclizes to a pyrroloisoquinoline (60). The pyrrole nucleus is then formylated under Vilsmeier-Haack conditions at position 5 and a proximate mesylated phenolic group is deprotected with base to yield a pen-tasubstituted pyrrole (61). Subsequent oxidative cyclization of this formylpyr-role produces the 5-lactone portion of lamellarin G trimethyl ether (36). This sequence allows for rapid and efficient analog synthesis as well as the synthesis of the natural product. 

Oxidative Cyclization of Substituted Phenols and Phenol Ethers. . 103... 

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

Not only phenols but also their 0-silyl derivatives and phenol ethers reacted similarly. In 0-silylated phenols bearing an aminoquinone moiety at their para-position BTI oxidation resulted in the formation of cyclized products in high yield [21] ... 

DAIB and BTIB oxidations of phenols proceed through aryloxyiodane 129 and/or aryloxenium ion 130 intermediates and are quite useful for the preparation of quinones, quinol ethers, and quinone acetals (e.g., Scheme 39) (88TL677, 92MI2, 93JCS(P1)1891, 01OR327). When phenols bearing nucleophilic side chains are used as substrates, such oxidations provide fertile ground for the assembly of heterocyclic structures. This can be accomplished by oxidative-cyclization reactions of different types. 

It has to be noted that 97 and 98 could not be obtained, by a biomimetic way, i.e. oxidative cyclization of the corresponding open chain phenols 137 and 138 respectively. In contrast the bromo compound 157 prepared from 154 could be induced to undergo photocyclization yielding a mixture of myricanone and its mono and dibenzyl ethers. 

Tyrosinase initiates conversion of phenol into o-benzoquinone, which forms Diels-Alder adducts. Employment of oxygen instead of other cooxidants in the oxidative cyclization of compounds containing a silyl enol ether and alkenyl side chain is desirable. ... 

The oxidative cyclization of substituted benzophenones using DDQ can give sensitive spirocoumaranones (eq 35). This phenolic cyclization is unusual in that it involves a highly constrained tetra-orf/zo-substituted benzophenone arrangement which, under other oxidative conditions, traditionally results in decomposition or further reaction to give diphenyl ether products through cleavage of the benzylic ketone. ... 

Additional examples of intramolecular oxidative coupling of phenolic ethers include the oxidative biaryl coupling of various N-substituted 1-benzyltetrahydroisoquinolines 313 to the corresponding aporphines 314 [374], the oxidative cyclization of 3,4-dimethoxyphenyl 3,4-dimethoxyphenylacetate (315) leading to the seven-membered lactone 316 [375] and the conversion of phenol ether derivatives 317 into the products of... 

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%. 

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