Confirmation by total synthesis of the revised structure of sporol: an application of cyclic thionocarbonate-initiated radical cyclization

✍ Scribed by Frederick E. Ziegler; Chester A. Metcalf III; Gayle Schulte

• Publisher: Elsevier Science
• Year: 1992
• Tongue: French
• Weight: 253 KB
• Volume: 33
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)79828-5

✦ Synopsis

The revised structure of sporol is confirmed by the synthesis of the racemate. Tri-nbutylstannyl radical induced fragmentation of a thionocarbonate and subsequent cyclization is employed to prepare a key component in the synthesis.

In 1988 we reported the synthesis of dioxolane 1, 2 which had been assigned as the smlcture of sporol.

After conducting detailed NMR analysis on structure 1 and natural sporol, we renamed dioxolane 1, neosporol, and the structure of sporol was reassigned as dioxane 2. 3 Because structures 1 and 2 differ only in a carbon-oxygen bond attachment, we have adapted our previous route to neosporol to the synthesis of sporol. Although the synthetic schemes parallel one another, construction of the precursor to the cyclopentene ring required a new strategy.

The synthetic plan required the allylic mesylate 8c (Scheme 1). Aldehyde 8a appeared to be a viable precursor but its preparation through an intramolecular aldol condensation was suspect owing to possible elimination reactions. Thionocarbonate-initiated radical cyclization proved to be a facile route to 8a.4 Alkynes 4s (1.7:l diastereomeric mixture; lR 2121 cm-l) were formed along with the diastereomeric allenes (IR 1958 cm-*) as an 11; 1 mixture from alcohol 36 by addition of the crude, intermediate homoglyceraldehyde acetonide to the organozinc reagent.7 The presence of the allenes was not considered detrimental because their anticipated radical cyclization products were expected to lead to the endocyclic, homoallylic isomer of 7a, which could be processed along with alcohol 7a. llnlike earlier studies,4 no products derived from cleavage of the primary C-0 bond of thionocarbonate 6 and cyclization of the resultant radical to give a six-membered ring were observed.8 The homoallyic alcohols 7a 3117