Imino Diels-Alder-based construction of a piperidine a-ring unit for total synthesis of the marine hepatotoxin cylindrospermopsin

Geoffrey R. Heintzelman, Steven M. Weinreb, Masood Parvez

Research output: Contribution to journalArticlepeer-review

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Abstract

The synthesis of a piperidine A-ring precursor to the alkaloid cylindrospermopsin (1) is described. The initial approach to the A-ring precursor focused on the imino Diels-Alder reaction of diene 8 with ethyl (N-tosylimino)acetate (9) to form the cycloadduct 10 as a single stereoisomer. However, all attempts to convert ester 10 to a requisite diene such as 5 were unsuccessful. An alternative strategy involved the Diels-Alder cycloaddition of N-tosylimine 9 with oxygenated diene 19 under either thermal or Lewis acid-catalyzed conditions to produce a mixture of cis and trans enones 20 and 21. Although the undesired cis-enone 20 was the major product under all reaction conditions, it could be converted to the desired trans enone 21 by acid-catalyzed isomerization. Copper-mediated conjugate addition of vinylmagnesium bromide to cis-enone 20 followed by stereoselective ketone reduction with L-Selectride produced alcohol 23, whose structure was confirmed by X-ray crystallography. Similarly, trans-enone 21 was converted to alcohol 25 whose structure and stereochemistry were also established by X-ray analysis. Alcohol 25 was then protected as the silyl ether 26, which was hydroborated at the terminal olefin to produce primary alcohol ester 28 having the stereochemistry and functionality needed for cylindrospermopsin.

Original languageEnglish (US)
Pages (from-to)4594-4599
Number of pages6
JournalJournal of Organic Chemistry
Volume61
Issue number14
StatePublished - Jul 12 1996

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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