Enantioselective carbon-nitrogen bond formation directed by a chiral cation Nicholas J. Hodson, Alexander Fanourakis, Arthur R. Lit, Robert J. Phipps 1 Yusuf Hamied Department of Chemistry, University of Cambridge, UK Enantioenriched amines are ubiquitous in industrially relevant and naturally occurring molecules. Current innovation in chiral amine synthesis is driven by the need to selectively functionalise simple starting materials, such as feedstock alkenes and C( sp 3 )-H bonds. 1 In this regard, catalytic nitrene insertion has been a useful tool for the synthesis of nitrogen-containing target compounds. 2 Although dirhodium tetracarboxylate catalysts have been at the forefront of progress in nitrene chemistry, 3 a general chiral ligand framework is yet to be realised for effective enantioselective reactions. We sought to address this in our previous study, which showcased a new family of chiral dirhodium tetracarboxylate catalysts. 4 Through sulfonation of the ligand scaffold, we introduced chirality by ion-pairing the anionic metal complex with a chiral cinchona alkaloid-derived cation. In this work, we have applied our family of ion-paired catalysts to an enantioselective aziridination of alkenyl alcohols. 5 The scope of the aziridination process was far more general than our previous amination report, 4 with simple aliphatic alkenyl alcohols used in addition to cis -styrenyl alcohols. Because of the breadth in alkene substitution patterns tolerated, we developed a practical mnemonic for predicting successful substrates and the stereochemistry of aziridine products. Lastly, we highlighted the synthetic versatility of aziridine intermediates by showcasing a variety of post-functionalisation protocols, including the formation of various oxa-spirocycles. In further studies, we have developed alternative chiral catalysts through rational variation of the position of the sulfonate group on the ligand skeleton. One family of next generation catalysts has enabled a successful C( sp 3 )-H amination to access enantioenriched γ -amino alcohols. 6 We have demonstrated the reaction tolerates electron- rich heteroarenes and is successful in desymmetrisation and diastereoselective modes.
References 1. A. Trowbridge, S. M. Walton and M. J. Gaunt, Chem. Rev., 2020, 120 , 2613–2692 2. J. L. Roizen, M. E. Harvey and J. Du Bois, Acc. Chem. Res., 2012, 45 , 911–922 3. C. G. Espino, K. W. Fiori, M. Kim and J. Du Bois, J. Am. Chem. Soc., 2004, 126 , 15378–15379 4. A. Fanourakis, B. D. Williams, K. J. Paterson and R. J. Phipps, J. Am. Chem. Soc., 2021, 143 , 10070–10076 5. A. Fanourakis, N. J. Hodson, A. R. Lit and R. J. Phipps, J. Am. Chem. Soc., 2023, 145 , 7516–7527 6. N. J. Hodson, A. Fanourakis and R. J. Phipps, unpublished results
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