Stereoselective and Stereospecific Triflate‐Mediated Intramolecular Schmidt Reaction: Ready Access to Alkaloid Skeletons

Gnägi, Lars; Arnold, Remo; Giornal, Florence; Jangra, Harish; Kapat, Ajoy; Nyfeler, Erich; Schärer, Robin M.; Zipse, Hendrik; Renaud, Philippe (2021). Stereoselective and Stereospecific Triflate‐Mediated Intramolecular Schmidt Reaction: Ready Access to Alkaloid Skeletons. Angewandte Chemie (International ed.), 60(18), pp. 10179-10185. Wiley-VCH 10.1002/anie.202016892

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The stereoselectivity and stereospecificity of the triflate-mediated intramolecular Schmidt reaction of substituted 3-(1-azidocyclohexyl)propanol derivatives leading to octahydro-1H-pyrrolo[1,2-a]azepine, the structural skeleton of several important families of alkaloids such as the Stemona alkaloids, has been examined. The reaction involves an initial intramolecular SN2 reaction between the azide moiety and the triflate affording an intermediate spirocyclic aminodiazonoium salt that undergoes the expected 1,2-shift/N2-elimination followed by hydride-mediated iminium salt reduction. Remarkably, chiral alcohols are converted to the azabicyclic derivative with no or limited racemization. The initial asymmetric alcohol center controls the diastereoselectivity of the whole process, leading to the formation of one out of the four possible diastereoisomers of disubstituted octahydro-1H-pyrrolo[1,2-a]azepine. The origin of the stereoselectivity is rationalized based on theoretical calculations. The concise synthesis of (−)-(cis)-3-propylindolizidine and (−)-(cis)-3-butyllehmizidine, two alkaloids found in the venom of workers of the ant Myrmicaria melanogaster, is reported.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Gnägi, Lars; Arnold, Remo; Schärer, Robin Marc and Renaud, Philippe

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1433-7851

Publisher:

Wiley-VCH

Language:

English

Submitter:

Franziska Bornhauser-Rufer

Date Deposited:

24 Jun 2021 12:05

Last Modified:

24 Jun 2021 12:14

Publisher DOI:

10.1002/anie.202016892

BORIS DOI:

10.48350/157098

URI:

https://boris.unibe.ch/id/eprint/157098

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