Thieme Chemistry Journals Awardees – Where Are They Now?
Carbene Organocatalysis for Stetter, Benzoin, Domino, and Ring-Expansion Reactions

^◊ These authors contributed equally to this work.

Abstract

N-Heterocyclic carbene catalysis allows the rapid formation of functionalized carbon–carbon bonds. Our group has spent the previous decade focusing on broadening practical applications of this type of catalysis. The design and discovery of novel reactivities and catalysts in our group can best be divided into work focusing on the Stetter, ring-expansion, and cross-benzoin reactions. Along with our expansion of the reaction scope, our introduction of novel bis(amino)cyclopropenylidene catalysts for the Stetter reaction successfully suppresses formation of side products, increasing synthetic utility. Concurrent work on ring-expansion reactions allows access to functionalized lactones and lactams. In addition to expanding the scope of the cross-benzoin reaction through use of α-ketoesters and α-amino aldehydes, the introduction of a new triazolylidene catalyst has allowed access to general chemoselective cross-benzoin reactions between aliphatic and aromatic aldehydes.

1 Introduction

2 Stetter Reactions

2.1 Domino Stetter Reactions

3 Ring-Expansion Reactions

4 Cross-Benzoin Reactions

5 Summary and Outlook

Key words

N-heterocyclic carbenes - organocatalysis - Stetter reaction - benzoin - enantioselective catalysis - ring expansion - cross-benzoin reaction

• References

• 1 Ukai T, Tanaka R, Dokawa T. J. Pharm. Soc. Jpn. 1943; 63: 296
• 2a Enders D, Niemeier O, Henseler A. Chem. Rev. 2007; 107: 5606
• 2b Moore JL, Rovis T. Carbene Catalysts . In Topics in Current Chemistry, Asymmetric Organocatalysis . Vol. 291. List B. Springer-Verlag; Berlin: 2009: 77
• 2c Phillips EM, Chan A, Scheidt KA. Aldrichimica Acta 2009; 42: 55
• 2d Chiang P.-C, Bode JW. N-Heterocyclic Carbenes: From Laboratory Curiosities to Efficient Synthetic Tools . Díez-González S. Royal Society of Chemistry; Cambridge: 2010: 339
• 2e Campbell CD, Ling KB, Smith AD. Carbene Catalysts . Vol. 32. Springer; Dordrecht: 2011: 263
• 2f Bugaut X, Glorius F. Chem. Soc. Rev. 2012; 41: 3511
• 2g Thai K, Sánchez-Larios E, Gravel M. N-Heterocyclic Carbenes in Organocatalysis. In Comprehensive Enantioselective Organocatalysis: Catalysts, Reactions, and Applications. Dalko PI. Wiley-VCH; Weinheim: 2013: 495-522
• 2h Hopkinson MN, Richter C, Schedler M, Glorius F. Nature 2014; 510: 485
• 2i Flanigan DM, Romanov-Michailidis F, White NA, Rovis T. Chem. Rev. 2015; 115: 9307
• 3 Breslow R. J. Am. Chem. Soc. 1958; 80: 3719
• 4a Stetter H, Schrecke M. Angew. Chem., Int. Ed. Engl. 1973; 12: 81

For reviews, see:
• 4b Stetter H. Angew. Chem., Int. Ed. Engl. 1976; 15: 639
• 4c Read de Alaniz J, Rovis T. Synlett 2009; 1189
• 4d Holmes JM, Gravel M. The Stetter Reaction . In Comprehensive Organic Synthesis II . Molander GA, Knochel P. Elsevier; Amsterdam: 2014
• 4e Yetra SR, Patra A, Biju AT. Synthesis 2015; 47: 1357 ; see also Ref. 2i

For select recent examples and studies of the Stetter reaction, see:
• 4f Ema T, Nanjo Y, Shiratori S, Terao Y, Kimura R. Org. Lett. 2016; 18: 5764
• 4g Fischer M, Harms K, Koert U. Org. Lett. 2016; 18: 5692
• 4h Lin Q, Li Y, Das DK, Zhang G, Zhao Z, Yang S, Fang X. Chem. Commun. 2016; 52: 6459
• 4i Rafinski Z. ChemCatChem 2016; 8: 2599
• 4j Rej RK, Acharyya RK, Nanda S. Tetrahedron 2016; 72: 4931
• 5 Rehbein J, Ruser SM, Phan J. Chem. Sci. 2015; 6: 6013
• 6 Enders D, Breuer K, Runsink J, Teles JH. Helv. Chim. Acta 1996; 79: 1899
• 7a Enders D, Han JW. Synthesis 2008; 3864
• 7b Enders D, Han JW, Henseler A. Chem. Commun. 2008; 3989
• 7c Liu Q, Perreault S, Rovis T. J. Am. Chem. Soc. 2008; 130: 14066
• 7d DiRocco DA, Oberg KM, Dalton DM, Rovis T. J. Am. Chem. Soc. 2009; 131: 10872
• 7e Liu Q, Rovis T. Org. Lett. 2009; 11: 2856
• 7f DiRocco DA, Rovis T. J. Am. Chem. Soc. 2011; 133: 10402
• 7g Jousseaume T, Wurz NE, Glorius F. Angew. Chem. Int. Ed. 2011; 50: 1410
• 8 Fang XQ, Chen XK, Lv H, Chi YR. Angew. Chem. Int. Ed. 2011; 50: 11782
• 9 Wurz NE, Daniliuc CG, Glorius F. Chem. Eur. J. 2012; 18: 16297
• 10 Sanchez-Larios E, Thai K, Bilodeau F, Gravel M. Org. Lett. 2011; 13: 4942
• 11 Yoshida ZI, Tawara Y. J. Am. Chem. Soc. 1971; 93: 2573
• 12a Lavallo V, Canac Y, Donnadieu B, Schoeller WW, Bertrand G. Science 2006; 312: 722
• 12b Lavallo V, Ishida Y, Donnadieu B, Bertrand G. Angew. Chem. Int. Ed. 2006; 45: 6652
• 13a Holschumacher D, Hrib CG, Jones PG, Tamm M. Chem. Commun. 2007; 3661
• 13b For the sole example of bis(amino)cyclopropenylidenes as organocatalysts since our own work, see: Ramanjaneyulu BT, Mahesh S, Anand RV. Org. Lett. 2015; 17: 3952
• 14 Wilde MM. D, Gravel M. Angew. Chem. Int. Ed. 2013; 52: 12651

For comprehensive reviews of the Stetter reaction in domino/cascade reactions, see:
• 15a Grossmann A, Enders D. Angew. Chem. Int. Ed. 2012; 51: 314
• 15b Yetra SR, Patra A, Biju AT. Synthesis 2015; 47: 1357
• 15c Vetica F, de Figueiredo RM, Orsini M, Tofani D, Gasperi T. Synthesis 2015; 47: 2139
• 16 Sanchez-Larios E, Gravel M. J. Org. Chem. 2009; 74: 7536
• 17a Sanchez-Larios E, Holmes JM, Daschner CL, Gravel M. Org. Lett. 2010; 12: 5772
• 17b Sanchez-Larios E, Holmes JM, Daschner CL, Gravel M. Synthesis 2011; 1896
• 18a Chow KY. K, Bode JW. J. Am. Chem. Soc. 2004; 126: 8126
• 18b Reynolds NT, de Alaniz JR, Rovis T. J. Am. Chem. Soc. 2004; 126: 9518
• 18c Chan A, Scheidt KA. Org. Lett. 2005; 7: 905
• 18d Sohn SS, Bode JW. Org. Lett. 2005; 7: 3873
• 18e Reynolds NT, Rovis T. J. Am. Chem. Soc. 2005; 127: 16406
• 18f Sohn SS, Bode JW. Angew. Chem. Int. Ed. 2006; 45: 6021
• 18g Zeitler K. Org. Lett. 2006; 8: 637
• 18h Alcaide B, Almendros P, Cabrero G, Ruiz MP. Chem. Commun. 2007; 4788
• 18i Bode JW, Sohn SS. J. Am. Chem. Soc. 2007; 129: 13798
• 18j Li GQ, Li Y, Dai LX, You SL. Org. Lett. 2007; 9: 3519
• 18k Vora HU, Rovis T. J. Am. Chem. Soc. 2007; 129: 13796
• 18l Vesely J, Ibrahem I, Zhao GL, Rios R, Cordova A. Angew. Chem. Int. Ed. 2007; 46: 778
• 18m Zhao GL, Cordova A. Tetrahedron Lett. 2007; 48: 5976
• 18n Du D, Wang ZW. Eur. J. Org. Chem. 2008; 4949
• 18o Ibrahem I, Zhao GL, Rios R, Vesely J, Sunden H, Dziedzic P, Cordova A. Chem. Eur. J. 2008; 14: 7867
• 18p Li GQ, Li Y, Dai LX, You SL. Adv. Synth. Catal. 2008; 350: 1258
• 18q Maki BE, Chan A, Scheidt KA. Synthesis 2008; 1306
• 18r Vora HU, Moncecchi JR, Epstein O, Rovis T. J. Org. Chem. 2008; 73: 9727
• 18s Phillips EM, Wadamoto M, Roth HS, Ott AW, Scheidt KA. Org. Lett. 2009; 11: 105
• 19a Wang L, Thai K, Gravel M. Org. Lett. 2009; 11: 891
• 19b Thai K, Wang L, Dudding T, Bilodeau F, Gravel M. Org. Lett. 2010; 12: 5708
• 20 Davidson RW. M, Fuchter MJ. Chem. Commun. 2016; 52: 11638
• 21a Izquierdo J, Hutson GE, Cohen DT, Scheidt KA. Angew. Chem. Int. Ed. 2012; 51: 11686
• 21b O’Bryan EA, Scheidt KA. Acyloin Coupling Reactions . In Comprehensive Organic Synthesis II . Marek I, Knochel P. Elsevier; Amsterdam: 2014. 2nd ed., Vol. 3, 621-655
• 21c Bugaut X. Benzoin and Aza-benzoin . In Comprehensive Organic Synthesis II . Marek I, Knochel P. Elsevier; Amsterdam: 2014. 2nd ed., Vol. 1, 424-470 ; see also Ref. 2i

For select recent examples and studies of the cross-benzoin reaction, see:
• 21d Collett CJ, Massey RS, Taylor JE, Maguire OR, O’Donoghue AC, Smith AD. Angew. Chem. Int. Ed. 2015; 54: 6887
• 21e Rafinski Z, Kozakiewicz A. J. Org. Chem. 2015; 80: 7468
• 21f Ramanjaneyulu BT, Mahesh S, Vijaya Anand R. Org. Lett. 2015; 17: 6
• 21g Sanchez-Diez E, Fernandez M, Uria U, Reyes E, Carrillo L, Vicario JL. Chem. Eur. J. 2015; 21: 8384
• 21h Li Y, Yang S, Wen G, Lin Q, Zhang G, Qiu L, Zhang X, Du G, Fang X. J. Org. Chem. 2016; 81: 2763
• 21i Rafinski Z. Tetrahedron 2016; 72: 1860
• 21j Shirke RP, Reddy V, Anand RV, Ramasastry SS. V. Synthesis 2016; 48: 1865
• 21k Zhang G, Yang S, Zhang X, Lin Q, Das DK, Liu J, Fang X. J. Am. Chem. Soc. 2016; 138: 7932
• 21l Wen G, Su Y, Zhang G, Lin Q, Zhu Y, Zhang Q, Fang X. Org. Lett. 2016; 18: 3980
• 22 Lapworth A. J. Chem. Soc. Trans. 1903; 83: 995
• 23a Stetter H, Dambkes G. Synthesis 1977; 403
• 23b Jin MY, Kim SM, Han H, Ryu DH, Yang JW. Org. Lett. 2011; 13: 880
• 23c Jin MY, Kim SM, Mao H, Ryu DH, Song CE, Yang JW. Org. Biomol. Chem. 2014; 12: 1547
• 24a O’Toole SE, Rose CA, Gundala S, Zeitler K, Connon SJ. J. Org. Chem. 2011; 76: 347
• 24b Piel I, Pawelczyk MD, Hirano K, Frohlich R, Glorius F. Eur. J. Org. Chem. 2011; 5475
• 24c Rose CA, Gundala S, Connon SJ, Zeitler K. Synthesis 2011; 190
• 24d Haghshenas P, Gravel M. Org. Lett. 2016; 18: 4518
• 24e Dünkelmann P, Kolter-Jung D, Nitsche A, Demir AS, Siegert P, Lingen B, Baumann M, Pohl M, Müller M. J. Am. Chem. Soc. 2002; 124: 12084
• 24f Collett CJ, Massey RS, Taylor JE, Maguire OR, O’Donoghue AC, Smith AD. Angew. Chem. Int. Ed. 2015; 54: 6887
• 25 Mathies AK, Mattson AE, Scheidt KA. Synlett 2009; 377
• 26a Hachisu Y, Bode JW, Suzuki K. J. Am. Chem. Soc. 2003; 125: 8432
• 26b Enders D, Niemeier O. Synlett 2004; 2111
• 26c Enders D, Niemeier O, Balensiefer T. Angew. Chem. Int. Ed. 2006; 45: 1463
• 26d Enders D, Niemeier O, Raabe G. Synlett 2006; 2431
• 26e Takikawa H, Hachisu Y, Bode JW, Suzuki K. Angew. Chem. Int. Ed. 2006; 45: 3492
• 26f Takikawa H, Suzuki K. Org. Lett. 2007; 9: 2713
• 26g Li Y, Feng Z, You SL. Chem. Commun. 2008; 2263
• 26h Ema T, Oue Y, Akihara K, Miyazaki Y, Sakai T. Org. Lett. 2009; 11: 4866
• 26i Enders D, Henseler A. Adv. Synth. Catal. 2009; 351: 1749
• 26j Enders D, Henseler A, Lowins S. Synthesis 2009; 4125
• 26k Enders D, Grossmann A, Fronert J, Raabe G. Chem. Commun. 2010; 46: 6282
• 26l Kuhl N, Glorius F. Chem. Commun. 2011; 47: 573
• 26m Takada A, Hashimoto Y, Takikawa H, Hikita K, Suzuki K. Angew. Chem. Int. Ed. 2011; 50: 2297
• 26n Rose CA, Gundala S, Fagan CL, Franz JF, Connon SJ, Zeitler K. Chem. Sci. 2012; 3: 735
• 26o Thai K, Langdon SM, Bilodeau F, Gravel M. Org. Lett. 2013; 15: 2214
• 27 Langdon SM, Wilde MM. D, Thai K, Gravel M. J. Am. Chem. Soc. 2014; 136: 7539
• 28 Langdon SM, Legault CY, Gravel M. J. Org. Chem. 2015; 80: 3597
• 29 Many triazolium–aldehyde adducts have been found to be stable, see: Collett CJ, Massey RS, Maguire OR, Batsanov AS, O’Donoghue AC, Smith AD. Chem. Sci. 2013; 4: 1514 . See also Ref. 27
• 30 Wilde MM. D, Gravel M. Org. Lett. 2014; 16: 5308