Angewandte Chemie - International Edition
Angewandte Chemie - International Edition
5 years ago

Enantioselective Silver and Amine Co-catalyzed Desymmetrizing Cycloisomerization of Alkyne-Linked Cyclohexanones

Enantioselective Silver and Amine Co-catalyzed Desymmetrizing Cycloisomerization of Alkyne-Linked Cyclohexanones
Darren J. Dixon, Swarup Datta, Rubén Manzano, Robert S. Paton
A silver(I) and amine co-catalyzed desymmetrization of 4-propargylamino cyclohexanones for the direct enantioselective synthesis of 2-azabicyclo[3.3.1]nonanes is described. Exploiting reactivity arising from dual activation of the pendant terminal alkyne by silver(I) and the ketone moiety through transient enamine formation, this synthetically relevant transformation is easy to perform, efficient and broad in scope. High enantioselectivity (up to 96 % ee) was achieved by exploiting a significant matching effect between the chirality of a cinchona alkaloid-derived aminophosphine ligand for the silver(I) salt and the 2-bis(aryl)methylpyrrolidine catalyst which was rationalized by DFT calculations. This allowed for the preparation of both enantiomers of the bicyclic product with near-identical stereocontrol. A matching effect between a chiral aminocatalyst and a chiral ligand for silver is exploited in the title reaction of 4-propargylamino cyclohexanones for the direct enantioselective synthesis of 2-azabicyclo[3.3.1]nonanes. The reaction is efficient, broad in scope and proceeds with high enantioselectivity.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201612048

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.