Economical Access to Diverse Enantiopure Tetrahydropyridines and Piperidines Enabled by Catalytic Borrowing Hydrogen
Teng Wei Ng
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544 Republic of Singapore
These authors contributed equally to this work.
Search for more papers by this authorRan Tao
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544 Republic of Singapore
Integrative Sciences and Engineering Programme, NUS Graduate School, National University of Singapore, 21 Lower Kent Ridge Road, Singapore, 119077 Singapore
These authors contributed equally to this work.
Search for more papers by this authorWilly Wei Li See
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544 Republic of Singapore
Search for more papers by this authorSi Bei Poh
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544 Republic of Singapore
Search for more papers by this authorCorresponding Author
Yu Zhao
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544 Republic of Singapore
Search for more papers by this authorTeng Wei Ng
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544 Republic of Singapore
These authors contributed equally to this work.
Search for more papers by this authorRan Tao
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544 Republic of Singapore
Integrative Sciences and Engineering Programme, NUS Graduate School, National University of Singapore, 21 Lower Kent Ridge Road, Singapore, 119077 Singapore
These authors contributed equally to this work.
Search for more papers by this authorWilly Wei Li See
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544 Republic of Singapore
Search for more papers by this authorSi Bei Poh
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544 Republic of Singapore
Search for more papers by this authorCorresponding Author
Yu Zhao
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544 Republic of Singapore
Search for more papers by this authorAbstract
We disclose herein a catalytic borrowing hydrogen method that enables an unprecedented, economical one-pot access to enantiopure tetrahydropyridines with minimal reagent use or waste formation. This method couples a few classes of readily available substrates with commercially available 1,3-amino alcohols, and delivers the valuable tetrahydropyridines of different substitution patterns free of N-protection. Such transformations are highly challenging to achieve, as multiple redox steps need to be realized in a cascade and numerous side reactions including a facile aromatization have to be overcome. Highly diastereoselective functionalizations of tetrahydropyridines also result in a general access to enantiopure di- and tri-substituted piperidines, which ranks the topmost frequent N-heterocycle in commercial drugs.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
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