Asymmetric synthesis of N-bridged [3.3.1] ring systems by phosphonium salt/Lewis acid relay catalysis

Jian-Ping Tan, Kehan Li, Boming Shen, Cheng Zhuang, Zanjiao Liu, Kai Xiao, Peiyuan Yu (), Bing Yi (), Xiaoyu Ren and Tianli Wang ()
Additional contact information
Jian-Ping Tan: Sichuan University
Kehan Li: Sichuan University
Boming Shen: Southern University of Science and Technology
Cheng Zhuang: Sichuan University
Zanjiao Liu: Sichuan University
Kai Xiao: Sichuan University
Peiyuan Yu: Southern University of Science and Technology
Bing Yi: Hunan Institute of Engineering
Xiaoyu Ren: Sichuan University
Tianli Wang: Sichuan University

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Optically pure pseudo-natural products (PNPs), particularly exemplified by azabicyclo[3.3.1]nonane molecules and their analogs provide an attractive platform for structure−activity relationship studies, and also lead new compound discovery in drug development. However, there are currently no examples of guiding catalytic asymmetric strategies available to construct such important PN-scaffolds, thus limiting their broad use. Here, we report a general and modular method for constructing these pseudo-natural N-bridged [3.3.1] ring systems via cascade process by bifunctional phosphonium salt/Lewis acid relay catalysis. A wide variety of substrates bearing an assortment of functional groups (59 examples) are compatible with this protocol. Other features include a [3 + 2] cyclization/ring-opening/Friedel-Crafts cascade pathway, excellent reactivities and stereoselectivities, easily available starting materials, step economy and scalability. The obtained enantioenriched products showed potential of preliminary anticancer activities. Insights gained from our studies are expected to advance general efforts towards the catalytic synthesis of challenging even unprecedented chiral PNPs, offering new opportunities for bioactive small-molecule discovery.

Date: 2022
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28001-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28001-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28001-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().