Enantioselective Construction of Sila-bicyclo[3.2.1] Scaffolds Bearing Both Carbon- and Silicon-Stereocenters
Abstract
A carbon-to-silicon switch in bioactive heterocycles has become a popular strategy in drug discovery. With the prevalence of chiral bridged biycyclic skeletons in numerous pharmacophores and alkaloids, the investigation of sila-bridged bicyclic skeletons as a potent bioisostere is significant. However, because organosilicon compounds are not available in nature, expanding their diversity fully depends on the development of effective synthetic methods. An optically active bridged bicyclic silicon scaffold has been clearly unprecedented to date due to the lack of an efficient synthetic method. Our study herein represents a rapid and enantioselective assembly of sila-bicyclo[3.2.1]octanes bearing both C- and Si-stereocenters, which involves the combined Heck reaction and enantioselective desymmetrization of silacyclopentenes with aryl halides in an intramolecular fashion. The synthetic utilities of these products and the origin of asymmetric induction are further investigated by diverse stereospecific downstream transformations and DFT calculations. We believe our study is highly sought after because of the prevalence of carbon congeners in biologically active molecules.
Additional Information
We are grateful for the financial support from the National Natural Science Foundation of China (22071114, 22022103, 21871146), Haihe Laboratory of Sustainable Chemical Transformations, the National Key Research and Development Program of China (2019YFA0210500; 2020YFA0711504), the "Frontiers Science Center for New Organic Matter", Nankai University (Grant Number 63181206), and the Fundamental Research Funds for the Central Universities and Nankai University.Additional details
- Eprint ID
- 118307
- Resolver ID
- CaltechAUTHORS:20221212-795726500.14
- 22071114
- National Natural Science Foundation of China
- 22022103
- National Natural Science Foundation of China
- 21871146
- National Natural Science Foundation of China
- Haihe Laboratory of Sustainable Chemical Transformations
- 2019YFA0210500
- National Key Research and Development Program of China
- 2020YFA0711504
- National Key Research and Development Program of China
- 63181206
- Nankai University
- Fundamental Research Funds for the Central Universities
- Created
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2023-01-12Created from EPrint's datestamp field
- Updated
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2023-01-12Created from EPrint's last_modified field