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Synthesis 2017; 49(10): 2205-2214
DOI: 10.1055/s-0036-1588716
DOI: 10.1055/s-0036-1588716
paper
Amine-Catalyzed Three-Component Cascade Reaction between Alcohols or Thiols, Activated Alkenes, and Enones: A Simple and Chemoselective Synthesis of Densely Functionalized Compounds
Further Information
Publication History
Received: 24 December 2016
Accepted after revision: 23 January 2017
Publication Date:
21 February 2017 (online)
![](https://www.thieme-connect.de/media/synthesis/201710/lookinside/thumbnails/ss-2016-h0882-op_10-1055_s-0036-1588716-1.jpg)
Abstract
A highly chemoselective three-component cascade reaction among alcohols or thiols, electron-deficient alkenes, and α,β-unsaturated ketones takes place under the catalysis of triethylamine, providing densely functionalized chain products in 44–99% yields. The transformation presumably proceeds through a sequential cascade of hetero-Michael/Michael reactions.
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1588716.
- Supporting Information
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References
- 1a Zhu J, Bienayme H. Multicomponent Reactions . Wiley-VCH; Weinheim: 2005
- 1b Orru RV. A, Greef M. Synthesis 2003; 1471
-
2a Yu J, Shi F, Gong L.-Z. Acc. Chem. Res. 2011; 44: 1156
- 2b de Graaff C, Ruijter E, Orru RV. A. Chem. Soc. Rev. 2012; 41: 3969
- 2c Volla CM. R, Atodiresei I, Rueping M. Chem. Rev. 2014; 114: 2390
- 3a Tannert R, Moran A, Melchiorre P In Comprehensive Enantioselective Organocatalysis: Catalysts, Reactions, and Applications . Dalko PI. Wiley-VCH; Weinheim: 2013: 1285
- 3b Marigo M, Melchiorre P. ChemCatChem 2010; 2: 621
- 3c Newhouse T, Baran PS, Hoffmann RW. Chem. Soc. Rev. 2009; 38: 310
- 4a Jung ME In Comprehensive Organic Synthesis . Vol. 4. Trost BM, Fleming I. Pergamon; Oxford: 1991: 1
- 4b Perlmutter P. Conjugate Addition Reactions in Organic Synthesis. Pergamon; Oxford: 1992
- 4c Tsogoeva SB. Eur. J. Org. Chem. 2007; 1701
- 5a Guo H.-C, Ma J.-A. Angew. Chem. Int. Ed. 2006; 45: 354
- 5b Vicario JL, Badia D, Carillo L. Synthesis 2007; 2065
- 5c Enders D, Luttgen K, Narine AA. Synthesis 2007; 959
- 5d Nising CF, Brase S. Chem. Soc. Rev. 2008; 37: 1218
- 5e Nising CF, Brase S. Chem. Soc. Rev. 2012; 41: 988
- 5f Sanchez-Rosello M, Acena JL, Simon-Fuentes A, del Pozo C. Chem. Soc. Rev. 2014; 43: 7430
- 5g Chauhan P, Mahanjan S, Enders D. Chem. Rev. 2014; 114: 8807
- 6a Stewart IC, Bergman RG, Toste FD. J. Am. Chem. Soc. 2003; 125: 8696
- 6b Bhuniya D, Mohan S, Narayanan S. Synthesis 2003; 1018
- 6c Kano C, Tanaka Y, Maruoka K. Tetrahedron Lett. 2006; 47: 3039
- 6d Kano C, Tanaka Y, Maruoka K. Tetrahedron 2007; 63: 8658
- 6e Zhang F.-L, Xu A.-W, Gong Y.-F, Wei M.-H, Yang X.-L. Chem. Eur. J. 2009; 15: 6815
- 6f Zu L, Zhang S, Xie H, Wang W. Org. Lett. 2009; 11: 1627
- 6g Bhanja C, Jena S, Nayak S, Mohapatra S. Beilstein J. Org. Chem. 2012; 8: 1668
- 6h Xia A.-B, Wu C, Wang T, Zhang Y.-P, Du X.-H, Zhong A.-G, Xu D.-Q, Xu Z.-Y. Adv. Synth. Catal. 2014; 356: 1753
- 7a McClure JD. J. Org. Chem. 1970; 35: 3045
- 7b Zhong C, Chen Y, Petersen JL, Akhmedov NG, Shi X. Angew. Chem. Int. Ed. 2009; 48: 1279
- 8a Zhang B, Cai L, Song H, Wang Z, He Z. Adv. Synth. Catal. 2010; 352: 97
- 8b Cai L, Zhang B, Wu G, Song H, He Z. Chem. Commun. 2011; 47: 1045
- 8c Zhou R, Wang J, Tian J, He Z. Org. Biomol. Chem. 2012; 10: 773
- 8d Zhou R, Wang J, Yu J, He Z. J. Org. Chem. 2013; 78: 10596
- 9a Aggarwal VA, Mereu A. Chem. Commun. 1999; 2311
- 9b Murtagh JE, McCooey SH, Connon SJ. Chem. Commun. 2005; 227
- 10 Only the coupling products 4 were formed when the reactions were run, even in methanol (2.0 mL) under otherwise the same conditions.
- 12 Frenanez I, Khiar N. Chem. Rev. 2003; 103: 3651
- 13 A control experiment also provided supportive evidence: In the absence of enone 2a and under the catalysis of Et3N (20 mol%), the hetero-Michael addition product of activated alkene 1a with methanol or ethanethiol was not observed at r.t. for 24 h.
- 14 Intermediates B and C may exist in the form of an ion pair. See also ref. 6a.
- 15 Addition of the strong base sodium methoxide only resulted in a complex reaction mixture (Table 1, entry 8).
- 16 Yadav JS, Reddy BV. S, Basak AK, Visali B, Narsaiah AV, Nagaiah K. Eur. J. Org. Chem. 2004; 546
- 17 Gras JL. Tetrahedron Lett. 1978; 32: 2955
For selected recent reviews, see
DBU is generally regarded as a hindered and non-nucleophilic base, although there are a few reports contesting this viewpoint: