Organocatalytic asymmetric azidation of sulfoxonium ylides: mild synthesis of enantioenriched α-azido ketones bearing a labile tertiary stereocenter |
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| Authors: | Wengang Guo Feng Jiang Shijia Li Jianwei Sun |
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| Affiliation: | Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou China.; Department of Chemistry and the Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration & Reconstruction, The Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon Hong Kong SAR China.; Shenzhen Research Institute, HKUST, No. 9 Yuexing 1st Rd, Shenzhen 518057 China |
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| Abstract: | Disclosed here is a catalytic asymmetric azidation reaction for the efficient synthesis of α-azido ketones bearing a labile tertiary stereocenter. With a superb chiral squaramide catalyst, a mild asymmetric formal H–N3 insertion of α-carbonyl sulfoxonium ylides proceeded with excellent efficiency and enantioselectivity. This organocatalytic process not only complements the previous α-azidation approaches for the formation of quaternary stereocenters and mostly for 1,3-dicarbonyl compounds, but also has advantages over the well-known metal-catalyzed asymmetric carbene insertion chemistry using α-diazocarbonyl compounds. Detailed mechanistic studies via control reactions and NMR studies provided important insights into the reaction pathway, which features reversible protonation and dynamic kinetic resolution. The curiosity in mechanism also led to the development of a simplified alternative protocol with a cheaper HN3 source.An organocatalytic asymmetric H–N3 insertion of α-carbonyl sulfoxonium ylides has been developed, providing efficient access to α-azido ketones bearing labile tertiary stereocenters and complementing the metal carbene insertion chemistry. |
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