Intramolecular Diels-Alder reactions of the retinoid side chain

• Published in: Tetrahedron Vol. 52; no. 2; pp. 405 - 424
• Main Authors: Shealy, Y. Fulmer, Riordan, James M., Frye, Jerry L., Campbell, Sheila R.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 08-01-1996
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/0040-4020(95)00898-5

Retinyl propynyl ether (RPE) undergoes an intramolecular Diels-Alder reaction to form a tetrahydroisobenzofuran derivative by addition of the alkyne group at positions 11 and 14 of the retinoid side chain. The Diels-Alder product can be isolated after RPE has been heated in refluxing ethanol. The Diels-Alder reaction also occurs very slowly in the solid state at low temperatures. The tetrahydroisobenzofuran is readily dehydrogenated to an aromatic retinoid, a 1,3-dihydroisobenzofuran. 2-Butynyl and 2-propenyl retinyl ethers undergo intramolecular cyclization to similar Diels-Alder products that can be isolated in yields of 50–60% after the ethers have been heated in refluxing toluene.
Retinyl 2-propynyl ether (
3b) and similar retinoids undergo an intramolecular Diels-Alder reaction at the 11,14-diene part of the retinoid side chain. The bicyclic Diels-Alder product (
4a) is readily dehydrogenated to an aromatic structure (
6a).
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