Simplifying Complex Scaffold Synthesis: Knoevenagel Adduct Allyl Anions as Easily Generated Multifunctional Reagents

Alexander J. Grenning

doi:10.1055/s-0036-1589954

Synlett, Inhaltsverzeichnis

Synlett 2017; 28(06): 633-639
DOI: 10.1055/s-0036-1589954

synpacts

Simplifying Complex Scaffold Synthesis: Knoevenagel Adduct Allyl Anions as Easily Generated Multifunctional Reagents

Alexander J. Grenning*

Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611-7200, USA eMail: grenning@ufl.edu

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

Abstract

Knoevenagel adduct allyl anions are easily generated and can serve as platforms for formal 1,3-difunctionalization. Summarized herein are a variety of reaction pathways that can be harnessed for multistep synthesis with emphasis on carbocycle synthesis.

1 Introduction

2 Formal 1,3-Difunctionalization Reactivity Modes: An Overview

3 γ-Alkylation/Deconjugative α-Alkylation

4 Deconjugative α-Alkylation/Pairing Sequences

5 Deconjugative α-Alkylation/Allylic Substitution

6 Deconjugative α-Alkylation/Allylic Transposition/Deconjugative α-Alkylation

7 Future Directions

8 Conclusions

Key words

Knoevenagel adducts - allyl anions - deconjugative α-alkylation - 1,3-difunctionalization - conjunctive reagents

Volltext

Referenzen

References
1 Jones G. Org. React. 1967; 15: 204
2 Knoevenagel E. Ber. Dtsch. Chem. Ges. 1898; 31: 2596

3a Cope AC, Hofmann CM, Wyckoff C, Hardenbergh E. J. Am. Chem. Soc. 1941; 63: 3452
3b Cope AC. J. Am. Chem. Soc. 1937; 59: 2327

4 For a review of alkylidenemalononitrile reagents, see: Kaur J, Chauhan P, Chimni SS. Org. Biomol. Chem. 2016; 14: 7832

For recent examples of alkylidnemalonate conjugate addition, see:

5a Yamada K, Matsumoto Y, Fujii S, Konishi T, Yamaoka Y, Takasu K. J. Org. Chem. 2016; 81: 3809
5b Liu Y, Shirakawa S, Maruoka K. Org. Lett. 2013; 15: 1230
5c Yamada K, Maekawa M, Akindele T, Nakano M, Yamamoto Y, Tomioka K. J. Org. Chem. 2008; 73: 9535
5d Zhao G.-L, Vesely J, Sun J, Christensen KE, Bonneau C, Cordova A. Adv. Synth. Catal. 2008; 350: 657
5e Rasappan R, Hager M, Gissibl A, Reiser O. Org. Lett. 2006; 8: 6099
5f Ooi T, Fujioka S, Maruoka K. J. Am. Chem. Soc. 2004; 126: 11790
5g Schuppan J, Minnaard AJ, Feringa BL. Chem. Commun. 2004; 792
5h Jorgensen KA. Synthesis 2003; 1117
5i Alexakis A, Benhaim C. Tetrahedron: Asymmetry 2001; 12: 1151

For recent examples of alkylidenemalonate cycloaddition, see:

6a Li T.-Z, Xie J, Jiang Y, Sha F, Wu X.-Y. Adv. Synth. Catal. 2015; 357: 3507
6b de Nanteuil F, Waser J. Angew. Chem. Int. Ed. 2013; 52: 9009
6c Jia Z.-J, Jiang H, Li J.-L, Gschwend B, Li Q.-Z, Yin X, Grouleff J, Chen Y.-C, Jorgensen KA. J. Am. Chem. Soc. 2011; 133: 5053
6d Deng H.-P, Wei Y, Shi M. Org. Lett. 2011; 13: 3348
6e Huang Z.-Z, Kang Y.-B, Zhou J, Ye M.-C, Tang Y. Org. Lett. 2004; 6: 1677

7a Cope AC, Hoyle KE. J. Am. Chem. Soc. 1941; 63: 733
7b Grossman RB, Varner MA. J. Org. Chem. 1997; 62: 5235
7c Nakamura H, Iwama H, Ito M, Yamamoto Y. J. Am. Chem. Soc. 1999; 121: 10850
7d Karlsen H, Songe PH, Sunsby LK, Hagen LC, Kolsaker P, Romming C. J. Chem. Soc., Perkin Trans. 1 2001; 497
7e Sato Y, Oonishi Y, Mori M. J. Org. Chem. 2003; 68: 9858
7f Bell M, Frisch K, Jørgensen KA. J. Org. Chem. 2006; 71: 5407

Seminal reports of γ-alkylation of Knoevenagel adducts:

8a Poulsen TB, Alemparte C, Jørgensen KA. J. Am. Chem. Soc. 2005; 127: 11614
8b Xue D, Chen Y.-C, Wang Q.-W, Cun L.-F, Zhu J, Deng J.-G. Org. Lett. 2005; 7: 5293
8c Poulsen TB, Bell M, Jørgensen KA. Org. Biomol. Chem. 2006; 4: 63
8d Xie J.-W, Yue L, Xue D, Ma X.-L, Chen Y.-C, Wu Y, Zhu J, Deng J.-G. Chem. Commun. 2006; 1563

Additional examples of γ-alkylation of Knoevenagel adducts:

9a Cheng C, Lu X, Ge L, Chen J, Cao W, Wu X, Zhao G. Org. Chem. Front. 2016;
9b Li X, Xu X, Wei W, Lin A, Yao H. Org. Lett. 2016; 18: 428
9c Wang X, Liu G, Xu X.-H, Shibata N, Tokunaga E, Shibata N. Angew. Chem. Int. Ed. 2014; 53: 827
9d Rout S, Ray SK, Unhale RA, Singh VK. Org. Lett. 2014; 16: 5568
9e Zhu X.-L, He W.-J, Yu L.-L, Cai C.-W, Zuo Z.-L, Qin D.-B, Liu Q.-Z, Jing L.-H. Adv. Synth. Catal. 2012; 354: 2965
9f Matsnev A, Noritake S, Nomura Y, Tokunaga E, Nakamura S, Shibata N. Angew. Chem. Int. Ed. 2010; 49: 572
9g Xiong X.-F, Jia Z.-J, Du W, Jiang K, Liu T.-Y, Chen Y.-C. Chem. Commun. 2009; 6994
9h Lu J, Zhou W.-J, Liu F, Loh T.-P. Adv. Synth. Catal. 2008; 350: 1796
9i Aleman J, Jacobsen CB, Frisch K, Overgaard J, Jorgensen KA. Chem. Commun. 2008; 632
9j Noritake S, Shibata N, Nakamura S, Toru T, Shiro M. Eur. J. Org. Chem. 2008; 3465
9k Liu T.-Y, Cui H.-L, Long J, Li B.-J, Wu Y, Ding L.-S, Chen Y.-C. J. Am. Chem. Soc. 2007; 129: 1878
9l Niess B, Joergensen KA. Chem. Commun. 2007; 1620
9m Xie J.-W, Chen W, Li R, Zeng M, Du W, Yue L, Chen Y.-C, Wu Y, Zhu J, Deng J.-G. Angew. Chem. Int. Ed. 2007; 46: 389

Examples of γ-alkylation/deconjugative α-alkylation:

10a Peng J, Huang X, Cui H.-L, Chen Y.-C. Org. Lett. 2010; 12: 4260
10b Cui H.-L, Peng J, Feng X, Du W, Jiang K, Chen Y.-C. Chem. Eur. J. 2009; 15: 1574
10c Xie J.-W, Yue L, Xue D, Ma X.-L, Chen Y.-C, Wu Y, Zhu J, Deng J.-G. Chem. Commun. 2006; 1563

11a Navaratne PV, Grenning A. J. Org. Biomol. Chem. 2017; 15: 69
11b Zhang W, Ghiviriga I, Grenning AJ. Tetrahedron 2016; 72: in press ; DOI: http://dx.doi.org/10.1016/j.tet.2016.11.055

12 Vertesaljai P, Navaratne PV, Grenning AJ. Angew. Chem. Int. Ed. 2016; 55: 317

13a Yamago S, Nakamura E. Org. React. 2002; 61: 1
13b Trost BM. Angew. Chem., Int. Ed. Engl. 1986; 25: 1
13c Trost BM, Chan DM. T. J. Am. Chem. Soc. 1979; 101: 6429

For examples of related [3,3] Cope rearrangements, see:

14a Cope AC, Hoyle KE, Heyl D. J. Am. Chem. Soc. 1941; 63: 1843
14b Nakamura H, Iwama H, Ito M, Yamamoto Y. J. Am. Chem. Soc. 1999; 121: 10850
14c Waetzig SR, Rayabharapu DK, Weaver JD, Tunge JA. Angew. Chem. Int. Ed. 2006; 45: 4977
14d Liu W.-B, Okamoto N, Alexy EJ, Hong AY, Tran K, Stoltz BM. J. Am. Chem. Soc. 2016; 138: 5234

15 Lahtigui O, Emmetiere F, Zhang W, Jirmo L, Toledo-Roy S, Hershberger JC, Macho JM, Grenning AJ. Angew. Chem. Int. Ed. 2016; 55: 15792

16a Comer E, Rohan E, Deng L, Porco JA. Org. Lett. 2007; 9: 2123
16b Dandapani S, Marcaurelle LA. Curr. Opin. Chem. Biol. 2010; 14: 362
16c Uchida T, Rodriquez M, Schreiber SL. Org. Lett. 2009; 11: 1559

17a Guijarro D, Yus M. Tetrahedron 1994; 50: 3447
17b Tsao J.-P, Tsai T.-Y, Chen I.-C, Liu H.-J, Zhu J.-L, Tsao S.-W. Synthesis 2010; 4242
17c Mattalia J.-M, Marchi-Delapierre C, Hazimeh H, Chanon M. ARKIVOC 2006; (iv): 90
17d Kang H.-Y, San Hong W, Seo Cho Y, Yeong Koh H. Tetrahedron Lett. 1995; 36: 7661

18 Otto N, Opatz T. Chem. Eur. J. 2014; 13064
19 Therien M, Fitzsimmons BJ, Scheigetz J, Macdonald D, Choo LY, Guay J, Falgueyret JP, Riendeau D. Bioorg. Med. Chem. Lett. 1993; 3: 2063

20a Afarinkia K, Vinader V, Nelson TD, Posner GH. Tetrahedron 1992; 48: 9111
20b Woodard BT, Posner GH. Adv. Cycloaddit. 1999; 5: 47

21 Roger R, Neilson DG. Chem. Rev. 1961; 61: 179
22 Kolb HC, VanNieuwenhze MS, Sharpless KB. Chem. Rev. 1994; 94: 2483