Practical Synthesis of Chiral N-Heterocyclic Carbene Triazolium Salts Containing a Hydroxy Functional Handle

Published as part of the Bürgenstock Special Section 2018 Future Stars in Organic Chemistry

Abstract

A library of functionalized chiral pyrrolidine-based N-heterocyclic carbene triazolium salts containing a hydroxy handle is prepared from readily accessible chiral (S)-pyroglutamic acid in eight steps. This improved synthetic protocol affords increased yields for known structures and 18 new NHCs are prepared by this method. The presence of a hydroxy handle offers potential for further functionalization and for non-covalent control over catalytic reactions in which the NHCs can serve as organocatalysts or ligands for organometallic catalysis.

Key words

N-heterocyclic carbenes - triazolium salts - organocatalysis - organomagnesium reagents - arylhydrazines - benzyl alcohol - protecting groups - desilylation

• References

• 1a Paul M, Breugst M, Neudorfl J.-M, Sunoj RB, Berkessel A. J. Am. Chem. Soc. 2016; 138: 5044
• 1b Langdon SM, Legault CY, Gravel M. J. Org. Chem. 2015; 80: 3597
• 1c Neel AJ, Hilton MJ, Sigman MS, Toste FD. Nature 2017; 543: 637
• 1d Davis HJ, Phipps RJ. Chem. Sci. 2017; 8: 864
• 1e Toste FD, Sigman MS, Miller SJ. Acc. Chem. Res. 2017; 50: 609
• 1f Ward TR, Collot J, Gradinaru J, Loosli A, Skander M, Letondor C, Joseph E, Klein G. Chimia 2003; 57: 586
• 1g Dougherty DA. Science 1996; 271: 163
• 2a O’Toole SE, Connon SJ. Org. Biomol. Chem. 2009; 7: 3584
• 2b Baragwanath L, Rose CA, Zeitler K, Connon SJ. J. Org. Chem. 2009; 74: 9214
• 3a Flanigan DM, Romanov-Michailidis F, White NA, Rovis T. Chem. Rev. 2015; 115: 9307
• 3b Massey RS, Collett CJ, Lindsay AG, Smith AD, O’Donoghue AC. J. Am. Chem. Soc. 2012; 134: 20421
• 3c Li Z, Li X, Cheng JP. J. Org. Chem. 2017; 82: 9675
• 3d Niu Y, Wang N, Munoz A, Xu J, Zeng H, Rovis T, Lee JK. J. Am. Chem. Soc. 2017; 139: 14917
• 3e Marion N, Diez-Gonzalez S, Nolan SP. Angew. Chem. Int. Ed. 2007; 46: 2988
• 3f Fu Z, Xu J, Zhu T, Leong WW, Chi YR. Nat. Chem. 2013; 5: 835
• 3g Enders D, Niemeier O, Henseler A. Chem. Rev. 2007; 107: 5606
• 3h Rovis T. Chem. Lett. 2008; 37: 2
• 4a Zheng C, Yao W, Zhang Y, Ma C. Org. Lett. 2014; 16: 5028
• 4b Ye S, He L, Zhang Y.-R, Huang X.-L. Synthesis 2008; 2825
• 4c White NA, Rovis T. J. Am. Chem. Soc. 2014; 136: 14674
• 4d Sun LH, Liang ZQ, Jia WQ, Ye S. Angew. Chem. Int. Ed. 2013; 52: 5803
• 4e Soeta T, Tabatake Y, Ukaji Y. Tetrahedron 2012; 68: 10188
• 4f Nakano Y, Lupton DW. Angew. Chem. Int. Ed. 2016; 55: 3135
• 4g Kerr MS, Read de Alaniz J, Rovis T. J. Org. Chem. 2005; 70: 5725
• 4h He M, Uc GJ, Bode JW. J. Am. Chem. Soc. 2006; 128: 15088
• 4i Fang X, Chen X, Lv H, Chi YR. Angew. Chem. Int. Ed. 2011; 50: 11782
• 4j He M, Struble JR, Bode JW. J. Am. Chem. Soc. 2006; 128: 8418
• 4k Wurz NE, Daniliuc CG, Glorius F. Chem. Eur. J. 2012; 18: 16297
• 4l Piel I, Steinmetz M, Hirano K, Frohlich R, Grimme S, Glorius F. Angew. Chem. Int. Ed. 2011; 50: 4983
• 4m Hopkinson MN, Richter C, Schedler M, Glorius F. Nature 2014; 510: 485
• 4n Hirano K, Biju AT, Piel I, Glorius F. J. Am. Chem. Soc. 2009; 131: 14190
• 4o Zhang Y.-R, He L, Wu X, Shao P.-L, Ye S. Org. Lett. 2008; 10: 277
• 4p Ling KB, Smith AD. Chem. Commun. 2011; 47: 373
• 5a Enders D, Han J. Tetrahedron: Asymmetry 2008; 19: 1367
• 5b Campbell CD, Concellón C, Smith AD. Tetrahedron: Asymmetry 2011; 22: 797
• 6 Acevedo CM, Kogut EF, Lipton MA. Tetrahedron 2001; 57: 6353
• 7a Zheng P, Gondo CA, Bode JW. Chem. Asian J. 2011; 6: 614
• 7b Enders D, Niemeier O, Balensiefer T. Angew. Chem. Int. Ed. 2006; 45: 1463
• 7c Enders D, Grossmann A, Fronert J, Raabe G. Chem. Commun. 2010; 46: 6282
• 7d Knight RL, Leeper FJ. J. Chem. Soc., Perkin Trans 1 1998; 1891
• 8 An L, Xiao YL, Zhang S, Zhang X. Angew. Chem. Int. Ed. 2018; 57: 6921
• 9 Krasovskiy A, Knochel P. Synthesis 2006; 890
• 10 Dhayalan V, Knochel P. Synthesis 2015; 47: 3246
• 11 Kumar Y, Jaiswal Y, Kumar A. Org. Lett. 2018; 20: 4964
• 12 Suzuki N, Fujita T, Ichikawa J. Org. Lett. 2015; 17: 4984