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Chiral aminophosphines derived from hydroxyproline and their application in allene–imine [4 + 2] annulation


A robust synthetic route from l-hydroxyproline (l-Hyp) to phosphines has established an expandable library of six chiral aminophosphines, which were then applied to the phosphine-catalyzed [4 + 2] allene–imine annulation. The enantioinduction in the annulations—induced by a purely steric effect—were moderate (up to 57% ee). A switch of the reaction site from the γ- to the β′-carbon atom of the allenoate was observed during the annulations performed using sterically demanding chiral phosphines.

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Financial support for this study was provided by the NIH (R01GM071779). We thank Dr. Saeed Khan (UCLA) for the crystallographic analyses. C.X. thanks Prof. Neil K. Garg and Sarah Anthony (UCLA) for sharing their SFC instrument.

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Correspondence to Ohyun Kwon.

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Khong, S.N., Xie, C., Wang, X. et al. Chiral aminophosphines derived from hydroxyproline and their application in allene–imine [4 + 2] annulation. J Antibiot 72, 389–396 (2019).

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