Domino Reactions of Tertiary Enamides in Organic Synthesis

Abstract

Studies in recent decade have shown that tertiary enamides, once thought of as unreactive and marginally useful enamine variants, are shelf-stable yet versatile nucleophilic intermediates in organic synthesis. Many compounds, especially N-heterocycles, have been synthesized by monofunctionalization reactions of tertiary enamides. By taking advantage of intramolecular and intermolecular interception of the putative acyliminium intermediates formed by the initial nucleophilic reactions of tertiary enamides, we have established several novel difunctionalization reaction methods for constructing diverse complex fused heterocyclic products. In this Account, we summarize our endeavors to develop difunctionalization reactions of tertiary enamides in a domino fashion.

1 Introduction

2 Strategic Considerations

3 Domino Reactions of Tertiary Enamides

3.1 Type I Domino Reactions

3.2 Type II Domino Reactions

3.3 Type III Domino Reactions

4 Conclusion and Perspectives

Key words

enamides - domino reaction - nucleophilic addition - asymmetric synthesis - N-heterocycles - alkaloids

• References

• 1a Stork G, Terrel R, Szmuszkovicz J. J. Am. Chem. Soc. 1954; 76: 2029
• 1b Stork G, Landesman HK. J. Am. Chem. Soc. 1956; 78: 5128
• 2 The Chemistry of Enamines . Rappoport Z. Wiley; Chichester: 1994
• 3a MacMillan DW. C. Nature 2008; 455: 304
• 3b Mukherjee S, Yang JW, Hoffmann S, List B. Chem. Rev. 2007; 107: 5471
• 4 Carbery DR. Org. Biomol. Chem. 2008; 6: 3455

For selected publications, see:
• 5a Shen R, Porco JA. Jr. Org. Lett. 2000; 2: 1333
• 5b Su S, Kakeya H, Osada H, Porco JA. Jr. Tetrahedron 2003; 59: 8931
• 6a Beltran F, Miesch L. Synthesis 2020; 52: 2497
• 6b Gigant N, Chausset-Boissarie L, Gillaizeau I. Chem. Eur. J. 2014; 20: 7548 ; and references cited therein
• 7 Milner PH, Coates NJ, Gilpin ML, Spear SR, Eggleston DS. J. Nat. Prod. 1996; 59: 400
• 8 Yang L, Deng G, Wang D.-X, Huang Z.-T, Zhu J, Wang M.-X. Org. Lett. 2007; 9: 1387
• 9a Wang M.-X, Lin S.-J, Liu C.-S, Zheng Q.-Y, Li J.-S. J. Org. Chem. 2003; 68: 4570
• 9b Wang M.-X. Acc. Chem. Res. 2015; 48: 602
• 10 Yang L, Zheng Q.-Y, Wang D.-X, Huang Z.-T, Wang M.-X. Org. Lett. 2008; 10: 2461
• 11 Yang L, Wang D.-X, Zheng Q.-Y, Pan J, Huang Z.-T, Wang M.-X. Org. Biomol. Chem. 2009; 7: 2628
• 12 Xu X.-M, Lei C.-H, Tong S, Zhu J, Wang M.-X. Org. Chem. Front. 2018; 5: 3138
• 13 Zhu W, Zhao L, Wang M.-X. J. Org. Chem. 2015; 80: 12047
• 14 Tong S, Yang X, Wang D.-X, Zhao L, Zhu J, Wang M.-X. Tetrahedron 2012; 68: 6492
• 15 Tong S, Wang D.-X, Zhao L, Zhu J, Wang M.-X. Angew. Chem. Int. Ed. 2012; 51: 4417
• 16 Yang L, Wang D.-X, Huang Z.-T, Wang M.-X. J. Am. Chem. Soc. 2009; 131: 10390
• 17 Tong S, Wang M.-X. Synlett 2019; 30: 483
• 18 Zhang X.-Y, Xu X.-M, Zhao L, You J, Zhu J, Wang M.-X. Tetrahedron Lett. 2015; 56: 3898
• 19 Zhu W, Tong S, Zhu J, Wang M.-X. J. Org. Chem. 2019; 84: 2870

For selected domino reactions of tertiary enamides developed by other research groups, see:
• 20a Satyanarayana G, Maichle-Mössmer C, Maier ME. Chem. Commun. 2009; 1571
• 20b Feltenberger JB, Hayashi R, Tang Y, Babiash ES. C, Hsung RP. Org. Lett. 2009; 11: 3666
• 20c Undeela S, Chandra R, Nanubolu JB, Menon RS. Org. Biomol. Chem. 2019; 17: 369
• 20d Beltran F, Miesch L. Org. Lett. 2019; 21: 1569
• 20e Zheng Y, Andna L, Bistri O, Miesch L. Org. Lett. 2020; 22: 6771
• 21 Xu X.-M, Zhao L, Zhu J, Wang M.-X. Angew. Chem. Int. Ed. 2016; 55: 3799
• 22 Xu X.-M, Xie M, Li J, Wang M.-X, Zhu J. Org. Chem. Front. 2021;
• 23 Zhen L, Tong S, Zhu J, Wang M.-X. J. Org. Chem. 2020; 85: 13211
• 24a Lehman AJ. Proc. Soc. Exp. Biol. Med. 1936; 33: 501
• 24b Dyke SF, Quessy SN. In The Alkaloids: Chemistry and Physiology, Vol. 18. Rodrigo RG. A. Academic Press; New York: 1981: 1
• 24c Sano T, Tsuda Y. In The Alkaloids: Chemistry and Pharmacology, Vol. 48. Cordell GA. Academic Press; New York: 1996: 249
• 25 Zhen L, Tong S, Zhu J, Wang M.-X. Chem. Eur. J. 2020; 26: 401
• 26 He L, Zhao L, Wang D.-X, Wang M.-X. Org. Lett. 2014; 16: 5972
• 27 He L, Liu H.-B, Zhao L, Wang D.-X, Wang M.-X. Tetrahedron 2015; 71: 523

For selected reviews, see:
• 28a Zhu J. Eur. J. Org. Chem. 2003; 1133
• 28b Dömling A. Chem. Rev. 2006; 106: 17
• 29 Lei C.-H, Wang D.-X, Zhao L, Zhu J, Wang M.-X. J. Am. Chem. Soc. 2013; 135: 4708
• 30 Lei C.-H, Wang D.-X, Zhao L, Zhu J, Wang M.-X. Chem. Eur. J. 2013; 19: 16981
• 31 Lei C.-H, Zhao L, Wang D.-X, Zhu J, Wang M.-X. Org. Chem. Front. 2014; 1: 909