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DOI: 10.1055/s-0028-1088146
Synthesis of 2-epi-Pumiliotoxin C via a Challenging Intramolecular Hydroamination Key Step
Publikationsverlauf
Publikationsdatum:
20. März 2009 (online)
Abstract
The synthesis of 2-epi-pumiliotoxin C was achieved in ten steps from cyclohexadiene oxide, using a challenging Cope-type hydroamination key step. This cyclization was performed on a mixture of two epimeric hydroxylamines, and a boat transition state is proposed to explain the kinetic preference observed for the cyclization of the epimer leading to N-hydroxy-epipumiliotoxin C.
Key words
total synthesis - alkaloids - amination - cyclization - heterocycles
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References and Notes
To the best of our knowledge, there are only few reported examples of a formation of six-membered piperidine ring via hydroamination onto an internal alkene: see ref. 4e,g,z for examples.
9O’Neil has reported cyclizations of unsaturated N-methyl-hydroxylamines leading to various six-membered ring systems: see ref. 8h-m. The cyclization to form morpholine N-oxides is compatible with distal alkene substitution: see ref. 8k,l.
10A first generation synthesis designed to provide access to various hydroamination precursors is shown in Scheme [8] .
16None of the hydroxylamine 1a could be recovered from the reaction mixture. ¹³C NMR analysis indicated that recovered hydroxylamine 1b was diastereomerically pure (within detection limits).
20This rationale is consistent with results from DFT calculations in simpler systems: Dr. Serge I. Gorelsky, private communication.
21Complete experimental procedures and characterization data for all new compounds can be obtained from the authors.