Adler-Becker oxidation

We thus postulated that the Adler-Becker oxidation could be used for this purpose (Figure 2). This approach would also benefit from the use of common intermediates previously synthesized during our Wessely oxidation campaign. Our new retrosynthetic route is outlined in Scheme 6 and apart from the key oxidative dearomatization step, it is identical to the previous one (Scheme 2). We envisioned that the more substituted site of the resulting epoxide could be selectively reduced after cycloaddition to reveal the desired C4-secondary alcohol found in vinigrol with correct stereochemistry. We were surprised to learn from the Adler-Becker oxidation literature that there were only a handful of examples employing secondary benzylic alcohols, and none of them were part of systematic studies in fact, the vast majority of published examples used only methylene alcohol derivatives as substrates. 

Acyclic and Pyran-Fused Adler-Becker Oxidation Substrates... 

Curious about these strained products, we wondered if more rigid starting structure could be used for the Adler-Becker/Diels-Alder sequence (Scheme 10). We decided to see if chromanones could be substituted with benzofuian stractures. SUylation of resorcinol 44 was followed by bromination and cyclizatiOTi to form benzofuran 46. As shown previously, triahylatiOTi and allyl ether deprotection yielded ketone 47, which was subsequently reduced to the benzylic alcohol however, this required much harsher conditions than those in the chromanone series (LiAlHj vs. NaBHj). Although less efficient than the chromanone derivative, the Adler-Becker oxidation proceeded to provide epoxy benzofuranone 48... 

SCHEME 10 Adler-Becker oxidation of benzofuranone framework. 

Although the Wessely and Adler-Becker oxidation explorations did not serve our vinigrol synthesis goals, we were pleased to have tested those hypotheses and learn the limitations of key chemical transformations. Still committed to... 

Results for the test Adler-Becker substrates, both precursors from our Wessely oxidation studies, are presented in Scheme 7. Interestingly, our first experiments revealed a dramatic difference in oxidation performance between acyclic and fused secondary benzylic alcohol substrates. While the acyclic substrate 30 afforded none of the epoxide quinone product 31, the fused pyran substrate 32 underwent oxidation smoothly to produce the desired epoxide product 32 in high yields. Encouraged by this excellent dearomatization... 

Becker H-D, Adler E (1961) Zur Oxydation mit Chinonen. Acta Chem Scand 15 218-219 Browning BL (1967) Methods of wood chemistry, Vol. II. Interscience, New York, 717-746 Chang H-m, Allan GG (1971) Oxidation. In Sarkanen KV, Ludwig CH (eds) Lignins. 

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