All-Carbon (4+2) Annulations Catalysed by N-Heterocyclic Carbenes

Abstract

Less than five years ago we reported the NHC-catalysed (4+2) annulation of dienol ethers and unsaturated acyl fluorides. From a mechanistic perspective, this reaction likely involves a vinylogous ­Michael addition followed by an aldol/β-lactonisation cascade. In this account, the discovery of this reaction and ensuing studies into its mechanism and utility in multistep synthesis will be examined. The subsequent development of chiral catalysts designed for this reaction and the achievement of a first-generation and later second-generation approach to an enantioselective variant of this reaction will be discussed. Finally, related redox isomerisation cascades leading to benzaldehydes will be introduced, as will reactions in the field of NHC catalysis that exploit similar reaction cascades.

1 Introduction

2 Reaction Design and Discovery

3 Mechanistic Studies and β-Lactone Interception

4 Enantioselective Cyclohexenyl β-Lactone Synthesis

5 Enantioselective Cyclohexadiene Synthesis

6 Redox Isomerisation

7 Related NHC Catalysis

8 Conclusions

Key words

NHC catalysis - vinylogous Michael - enantioselective - cascade catalysis - redox isomerisation

• References


For reactions that likely involve Brønsted base chemistry see:
• 1a Grasa GA, Kissling RM, Nolan SP. Org. Lett. 2002; 4: 3583
• 1b Nyce GW, Lamboy JA, Connor EF, Waymouth RM, Hedrick JL. Org. Lett. 2002; 4: 3587

For NHC catalyzed transesterification with amino alcohols and mechanistic comments see:
• 1c Movassaghi M, Schmidt MA. Org. Lett. 2005; 7: 2453
• 1d Schmidt MA, Müller P, Movassaghi M. Tetrahedron Lett. 2008; 49: 4316

For Lewis base addition to ahydrides see:
• 1e Sun X, Ye S, Wu J. Eur. J. Org. Chem. 2006; 4787

For Lewis base addition to enol carbonates see:
• 1f Thomson JE, Rix K, Smith AD. Org. Lett. 2006; 8: 3785
• 2 Ryan SJ, Candish L, Lupton DW. J. Am. Chem. Soc. 2009; 131: 14176
• 3 Candish L, Lupton DW In Strategies and Tactics in Organic Synthesis . Vol. 11. Harmata M. Elsevier; Amsterdam: 2015: 309
• 4 Ryan SJ, Candish L, Lupton DW. J. Am. Chem. Soc. 2011; 133: 4694

For selected examples from the Chi group with ester substrates see:
• 5a Hao L, Du Y, Lv H, Chen X, Jiang H, Shao Y, Chi YR. Org. Lett. 2012; 14: 2154
• 5b Hao L, Chen S, Xu J, Tiwari B, Fu Z, Li T, Lim J, Chi YR. Org. Lett. 2013; 15: 4956
• 5c Chen S, Hao L, Zhang Y, Tiwari B, Chi YR. Org. Lett. 2013; 15: 5822
• 5d Fu Z, Xu J, Zhu T, Leong WW. Y, Chi YR. Nat. Chem. 2013; 5: 835
• 5e Xu J, Jin Z, Chi YR. Org. Lett. 2013; 15: 5028
• 5f Fu Z, Wu X, Chi YR. Org. Chem. Front. 2016; 3: 145
• 5g Chen X, Fong JZ. M, Xu J, Mou C, Lu Y, Yang S, Song B.-A, Chi YR. J. Am. Chem. Soc. 2016; 138: 7212

For a recent example from the Xu group see:
• 5h Xu J, Yuan S, Miao M. Org. Lett. 2016; 18: 3822

For in situ anhydride formation and reaction see:
• 5i Lee A, Younai A, Price CK, Izquierdo J, Mishra RK, Scheidt KA. J. Am. Chem. Soc. 2014; 136: 10589
• 5j Chen X.-Y, Gao Z.-H, Song C.-Y, Zhang C.-L, Wang Z.-X, Ye S. Angew. Chem. Int. Ed. 2014; 53: 11611
• 5k Jin Z, Chen S, Wang Y, Zheng P, Yang S, Chi YR. Angew. Chem. Int. Ed. 2014; 53: 13506

For a selection of recent reviews of NHC catalysis see:
• 6a Enders D, Niemeier O, Henseler A. Chem. Rev. 2007; 107: 5606
• 6b Douglas J, Churchill G, Smith AD. Synthesis 2012; 44: 2295
• 6c Bugaut X, Glorius F. Chem. Soc. Rev. 2012; 41: 3511
• 6d Izquierdo J, Hutson GE, Cohen DT, Scheidt KA. Angew. Chem. Int. Ed. 2012; 51: 11686
• 6e Ryan SJ, Candish L, Lupton DW. Chem. Soc. Rev. 2013; 42: 4906
• 6f Hopkinson MN, Richter C, Schedler M, Glorius F. Nature 2014; 510: 485
• 6g Chauhan P, Enders D. Angew. Chem. Int. Ed. 2014; 53: 1485
• 6h Flanigan DM, Romanov-Michailidis F, White NA, Rovis T. Chem. Rev. 2015; 115: 9307

For selected reviews of dienamine catalysis see:
• 7a Ramachary DB, Reddy YV. Eur. J. Org. Chem. 2012; 865
• 7b Jiang H, Albrecht Ł, Jørgensen KA. Chem. Sci. 2013; 4: 2287

For all-carbon (4+2) annulations through vinylogous Michael aldol-type cascades see:
• 7c Bench BJ, Liu C, Evett CR, Watanabe CM. H. J. Org. Chem. 2006; 71: 9458
• 7d Hong B.-C, Wu M.-F, Tseng H-C, Huang G.-F, Su C.-F, Liao J.-H. J. Org. Chem. 2007; 72: 8459
• 7e Stiller J, Poulsen PH, Cruz DC, Dourado J, Davis RL, Jørgensen KA. Chem. Sci. 2014; 5: 2052
• 7f Weber AK, Schachtner J, Fichtler R, Leerman TM, Neudörfl JM, von Wangelin AJ. Org. Biomol. Chem. 2014; 12: 5267
• 8 For a study on the unsaturated acyl azolium as a conjugate acceptor see: Samanta RC, Maji B, De Sarkar S, Bergander K, Fröhlich R, Mück-Lichtenfeld C, Mayr H, Studer A. Angew. Chem. Int. Ed. 2012; 51: 5234

For NHC-catalyzed reactions involving β-lactones see:
• 9a Nair V, Vellalath S, Poonoth M, Suresh E. J. Am. Chem. Soc. 2006; 128: 8736
• 9b Chiang P.-C, Kaeobamrung J, Bode JW. J. Am. Chem. Soc. 2007; 129: 3520
• 9c Wadamoto M, Phillips EM, Reynolds TE, Scheidt KA. J. Am. Chem. Soc. 2007; 129: 10098
• 9d He M, Bode JW. J. Am. Chem. Soc. 2008; 130: 418
• 9e Kaeobamrung J, Bode JW. Org. Lett. 2009; 11: 677
• 9f Phillips EM, Roberts JM, Scheidt KA. Org. Lett. 2010; 12: 2830
• 10 For related reports see: Bappert E, Müller P, Fu GC. Chem. Commun. 2006; 2604

For a useful review on 2-pyrones and 2-pyridones in synthesis see:
• 11a Afarinkia K, Vinader V, Nelson TD, Posner GH. Tetrahedron 1992; 48: 9111

For recent examples in catalysis see:
• 11b Singh RP, Bartelson K, Wang Y, Su H, Lu X, Deng L. J. Am. Chem. Soc. 2008; 130: 2422
• 11c Soh JY.-T, Tan C.-H. J. Am. Chem. Soc. 2009; 131: 6904

For enzymatic versions see:
• 11d Ose T, Watanabe K, Mie T, Honma M, Watanabe H, Yao M, Oikawa H, Tanaka I. Nature 2003; 422: 185
• 11e Serafimov JM, Westfeld T, Meier BH, Hilvert D. J. Am. Chem. Soc. 2007; 129: 9580

For selected studies in total synthesis see:
• 11f Martin SF, Rüeger H, Williamson SA, Grzejszczak S. J. Am. Chem. Soc. 1987; 109: 6124
• 11g Baran PS, Burns NZ. J. Am. Chem. Soc. 2006; 128: 3908
• 11h Nelson HM, Stoltz BM. Org. Lett. 2008; 10: 25

For methodologies see:
• 11i Li L, Chase CE, West FG. Chem. Commun. 2008; 4025
• 11j Afarinkia K, Abdullahi MH, Scowen IJ. Org. Lett. 2010; 12: 5564
• 12 Biswas A, De Sarkar S, Fröhlich R, Studer A. Org. Lett. 2011; 13: 4966
• 13 We would like to thank the groups of Tomislav Rovis, Jonathan Morris and Michel Gravel for their generous donation of homochiral NHC catalysts.
• 14 Ryan SJ, Stasch A, Paddon-Row MN, Lupton DW. J. Org. Chem. 2012; 77: 1113
• 15 Candish L, Forsyth CM, Lupton DW. Angew. Chem. Int. Ed. 2013; 52: 9149
• 16 Levens A, An F, Breugst M, Mayr H, Lupton DW. Org. Lett. 2016; 18: 3566
• 17 Candish L, Levens A, Lupton DW. J. Am. Chem. Soc. 2014; 136: 14397
• 18 Levens A, Zhang C, Candish L, Forsyth CM, Lupton DW. Org. Lett. 2015; 17: 5332
• 19 Zeitler K. Org. Lett. 2006; 8: 637
• 20 Candish L, Levens A, Lupton DW. Chem. Sci. 2015; 6: 2366
• 21a Zhu T, Zheng P, Mou C, Yang S, Song B.-A, Chi YR. Nat. Commun. 2014; 5: 5027
• 21b Zhu T, Mou C, Li B, Smetankova M, Song B.-A, Chi YR. J. Am. Chem. Soc. 2015; 137: 5658
• 22 Bera S, Samanta RC, Daniliuc CG, Studer A. Angew. Chem. Int. Ed. 2014; 53: 9622
• 23a Bera S, Daniliuc CG, Studer A. Org. Lett. 2015; 17: 4940
• 23b Liang Z.-Q, Wang D.-L, Zhang H.-M, Ye S. Org. Lett. 2015; 17: 5140