[3]Dendralenes: Synthesis, Reactivity Studies and Employment in Diversity-Oriented Synthesis of Complex Polycyclic Scaffolds

Abstract

[3]Dendralenes are exquisite molecules as they exhibit enormous potential for the rapid generation of architecturally esoteric scaffolds when subjected to tandem Diels–Alder reactions, but their synthesis is a tall order. In conjunction with diversity-oriented synthesis, [3]dendralenes satisfy the potential demand for simultaneous and efficient synthesis of intricate collections of molecules that exhibit a range of activities for lead generation in drug discovery. This account chronicles our roller-coaster journey and systematic approach beginning from the synthesis of extremely unstable, non-isolable [3]dendralenes through moderately stable examples and then finally, highly functionalized, stable [3]dendralenes via sequential methylenation (using dimethylsulfonium methylide) and Horner–Wadsworth–Emmons olefination. It also describes the study of the attributes affecting their stability and reactivity with various dienophiles. In addition, it reports on how these dendralenes, upon astute maneuvering, can be engaged in a diene-transmissive Diels–Alder (DTDA) sequence, thus harnessing their full potential by construction of a small but diverse library of complex frameworks in a quick and efficient manner, with step and atom economy.

1 Introduction

2 Literature Methods for [3]Dendralene Synthesis

3 Our Tryst with [3]Dendralenes

3.1 Serendipitous Olefination with the Corey–Chaykovsky Ylide

3.2 Synthesis of [3]Dendralenes and Reactivity/Stability Studies

3.3 Diels–Alder Reactions of [3]Dendralenes

3.4 Tuning of [3]Dendralenes for the DTDA Reactions

3.5 Diversity-Oriented Synthesis with [3]Dendralenes

3.6 Rationalization of Factors Governing the Stability and Reactivity of [3]Dendralenes

4 Conclusions

Key words

dimethylsulfonium methylide - olefination - [3]dendralenes - diene-transmissive Diels–Alder (DTDA) - diversity-oriented synthesis (DOS) - polycyclic

• References

• 1 Hopf H. Nature 2009; 460: 183
• 2 Pollack L. Uncovering a Hidden Family of States: Quantum Biology of the Polyenes . Beckman Institute; University of Illinois at Urbana-Champaign, February: 2014
• 3 Madden KS. Mosa FA. Whiting A. Org. Biomol. Chem. 2014; 12: 7877
• 4a Tykwinski RR. Gholami M. Eisler S. Zhao Y. Melin F. Echegoyen L. Pure Appl. Chem. 2008; 80: 621
• 4b Hopf H. Maas G. Angew. Chem., Int. Ed. Engl. 1992; 31: 931
• 5 Scott AP. Agranat I. Biedermann PU. Riggs NV. Radom L. J. Org. Chem. 1997; 62: 2026
• 6 Januszewski JA. Tykwinski RR. Chem. Soc. Rev. 2014; 43: 3184
• 7a Hopf H. Sherburn MS. Angew. Chem. Int. Ed. 2012; 51: 2298
• 7b Sherburn MS. Acc. Chem. Res. 2015; 48: 1961
• 7c Cross Conjugation: Modern Dendralene, Radialene and Fulvene Chemistry . Hopf H. Sherburn MS. Wiley-VCH; Weinheim: 2016
• 8a Bailey WJ. Economy J. Hermes ME. J. Org. Chem. 1962; 27: 3295
• 8b Blume RC. US Patent 3,860,669, 1973
• 8c Diakoumakos CD. Mikroyannidis JA. J. Appl. Polym. Sci. 1994; 53: 201
• 8d Tekenaka K. Amamoto S. Kishi H. Takeshita H. Miya M. Shiomi T. Macromolecules 2013; 46: 7282
• 9a Kajiwara Y. Hino S. Misaki Y. Bull. Chem. Soc. Jpn. 2012; 85: 830
• 9b Hasegawa M. Watanabe M. Misaki Y. J. Synth. Org. Chem. Jpn. 2013; 71: 1268
• 9c Breiten B. Jordan M. Taura D. Zalibera M. Griesser M. Confortin D. Boudon C. Gisselbrecht J.-P. Schweizer WB. Gescheidt G. Diederich F. J. Org. Chem. 2013; 78: 1760
• 10a Kanibolotsky AL. Forgie JC. McEntee GJ. Talpur MM. A. Skabara PJ. Westgate TD. J. McDouall JJ. Auinger WM. Coles SJ. Hursthouse MB. Chem. Eur. J. 2009; 15: 11581
• 10b Amaresh RR. Liu D. Konovalova T. Lakshmikantham MV. Cava MP. Kispert LD. J. Org. Chem. 2001; 66: 7757
• 10c Bryce MR. Coffin MA. Skabara PJ. Moore AJ. Batsanov AS. Howard JA. K. Chem. Eur. J. 2000; 6: 1955
• 11a Radovic BS. Careri M. Mangia A. Musci M. Gerboles M. Anklam E. Food Chem. 2001; 72: 511
• 11b Ravinder P. Subramanian V. Theor. Chem. Acc. 2012; 131: 1128
• 12a Radovic BS. Careri M. Mangia A. Musci M. Gerboles M. Anklam E. Food Chem. 2001; 72: 511
• 12b Rahman M. Yusaf M. Chowdhury JU. Wahab MA. Bangladesh J. Sci. Ind. Res. 1987; 22: 152
• 12c Sefton MA. Francis IL. Williams PJ. J. Food Sci. 1994; 59: 142
• 12d Arnone A. Cardillo R. Dimodugno V. Nasini G. J. Chem. Soc., Perkin Trans. 1 1989; 1995
• 13 Tsuge O. Wada E. Kanemasa S. Chem. Lett. 1983; 12: 1525
• 14a Blomquist AT. Verdol JA. J. Am. Chem. Soc. 1955; 77: 81
• 14b Bailey WJ. Economy J. J. Am. Chem. Soc. 1955; 77: 1133
• 15a Blomquist AT. Verdol JA. J. Am. Chem. Soc. 1955; 77: 1806
• 15b Bailey WJ. Cunov CH. Nicholas L. J. Am. Chem. Soc. 1955; 77: 2787
• 16 Vdovin VM. Finkel’shtein ESh. Shelkov AV. Yatsenko MS. Russ. Chem. Bull. 1986; 35: 2364
• 17 Martin H.-D. Eckert-Maksic M. Mayer B. Angew. Chem., Int. Ed. Engl. 1980; 19: 807
• 18 Cadogan JI. G. Cradock S. Gillam S. Gosney I. J. Chem. Soc., Chem. Commun. 1991; 114
• 19 Priebe H. Hopf H. Angew. Chem., Int. Ed. Engl. 1982; 21: 286
• 20 Fielder S. Rowan DD. Sherburn MS. Angew. Chem. Int. Ed. 2000; 39: 4331
• 21a Payne AD. Bojase G. Paddon-Row MN. Sherburn MS. Angew. Chem. Int. Ed. 2009; 48: 4836
• 21b Bradford TA. Payne AD. Willis AC. Paddon-Row MN. Sherburn MS. Org. Lett. 2007; 9: 4861
• 21c Miller NA. Willis AC. Paddon-Row MN. Sherburn MS. Angew. Chem. Int. Ed. 2007; 46: 937
• 22 Woo S. Squires N. Fallis AG. Org. Lett. 1999; 1: 573
• 23 Bradford TA. Payne AD. Willis AC. Paddon-Row MN. Sherburn MS. J. Org. Chem. 2010; 75: 491
• 24 Tan SM. Willis AC. Paddon-Row MN. Sherburn MS. Angew. Chem. Int. Ed. 2016; 55: 3081
• 25a Pronin SV. Shenvi RA. J. Am. Chem. Soc. 2012; 134: 19604
• 25b Lu H.-H. Pronin SV. Antonova-Koch Y. Meister S. Winzeler EA. Shenvi RA. J. Am. Chem. Soc. 2016; 138: 7268
• 26a Le Nôtre J. Martinez AA. Dixneuf PH. Bruneau C. Tetrahedron 2003; 59: 9425
• 26b Beydoun K. Zhang H.-J. Sundararaju B. Demerseman B. Achard M. Xi Z. Bruneau C. Chem. Commun. 2009; 6580
• 26c Srour H. Abidi K. Sahli Z. Sundararaju B. Hamdi N. Achard M. Bruneau C. ChemCatChem 2011; 3: 1876
• 27 Kang B. Kim D.-H. Do Y. Chang S. Org. Lett. 2003; 5: 3041
• 28 Reider CJ. Winberg KJ. West FG. J. Org. Chem. 2011; 76: 50
• 29 Thies N. Haak E. Angew Chem. Int. Ed. 2015; 54: 4097
• 30a Englert M. Jolly PW. Wilke G. Angew. Chem. Int. Ed. 1972; 11: 136
• 30b Pasto DJ. Huang NZ. Organometallics 1985; 4: 1386
• 31 Arisawa M. Sugihara T. Yamaguchi M. Chem. Commun. 1998; 2615
• 32 Brummond KM. Chen H. Sill P. You L. J. Am. Chem. Soc. 2002; 124: 15186
• 33 Shimp HL. Hare A. McLaughlin M. Micalizio GC. Tetra­hedron 2008; 64: 6831
• 34 Miura T. Biyajima T. Toyoshima T. Murakami M. Beilstein J. Org. Chem. 2011; 7: 578
• 35 Wang H. Beiring B. Yu D.-G. Collins KD. Glorius F. Angew. Chem. Int. Ed. 2013; 52: 12430
• 36 Sakashita K. Shibata Y. Tanaka K. Angew. Chem. Int. Ed. 2016; 55: 6753
• 37 Mao M. Zhang L. Chen Y.-Z. Zhu J. Wu L. ACS Catal. 2017; 7: 181
• 38 Lippincott D. Roscoe J. Linstadt TH. Maser MR. Lipshutz BH. Angew. Chem. Int. Ed. 2017; 56: 847
• 39 Zhang T. Song C. Meng Y. Chen P. Xu H. Chang J. J. Org. Chem. 2017; 82: 9905
• 40 Qiu Y. Posevins D. Bäckvall J.-E. Angew. Chem. Int. Ed. 2017; 56: 13112
• 41a Corey EJ. Chaykovsky M. J. Am. Chem. Soc. 1965; 87: 1353
• 41b Aubé J. In Comprehensive Organic Synthesis: Selectivity, Strategy, and Efficiency in Modern Synthetic Chemistry . Vol. 1. Trost BM. Fleming I. Chap. 3.2 Pergamon; Oxford: 1991: 822
• 41c Li A.-H. Dai L.-X. Aggarwal VK. Chem. Rev. 1997; 97: 2341
• 41d Name Reactions in Heterocyclic Chemistry . Li J.-J. Corey EJ. John Wiley & Sons; Hoboken: 2005: 2
• 42a Ghosh SK. Singh R. Date SM. Chem. Commun. 2003; 636
• 42b Date SM. Singh R. Ghosh SK. Org. Biomol. Chem. 2005; 3: 3369
• 43a Singh R. Ghosh SK. Org. Lett. 2007; 9: 5071
• 43b Singh R. Ghosh SK. Tetrahedron 2010; 66: 2284
• 44a Date SM. Ghosh SK. Angew. Chem. Int. Ed. 2007; 46: 386
• 44b Date SM. Ghosh SK. Bull. Chem. Soc. Jpn. 2004; 77: 2099
• 44c Chowdhury R. Ghosh SK. Eur. J. Org. Chem. 2008; 3868
• 45 Singh R. Ghosh SK. Chem. Commun. 2011; 47: 10809
• 46 Singh R. Ghosh SK. Tetrahedron: Asymmetry 2014; 25: 57
• 47a Paddon-Row MN. Sherburn MS. Chem. Commun. 2012; 48: 832
• 47b Toombs-Ruane H. Pearson EL. Paddon-Row MN. Sherburn MS. Chem. Commun. 2012; 48: 6639
• 48 Naidu GS. Singh R. Kumar M. Ghosh SK. RSC Adv. 2016; 63: 37136
• 49 Singh R. Naidu GS. Ghosh SK. Proc. Natl. Acad. Sci., India Sect. A: Phys. Sci. 2016; 86: 619
• 50 Kundu PK. Ghosh SK. Tetrahedron 2010; 66: 8562
• 51 Naidu GS. Singh R. Kumar M. Ghosh SK. J. Org. Chem. 2017; 82: 3648
• 52 Burke MD. Schreiber SL. Angew. Chem. Int. Ed. 2004; 43: 46
• 53a Spring DR. Org. Biomol. Chem. 2003; 1: 3867
• 53b Spandl RJ. Díaz-Gavilán M. O’Connell KM. G. Thomas GL. Spring DR. Chem. Rec. 2008; 8: 129
• 53c O’Connell KM. G. Galloway WR. D. Spring DR. The Basics of Diversity-Oriented Synthesis. In Diversity-Oriented Synthesis: Basics and Applications in Organic Synthesis, Drug Discovery, and Chemical Biology. 1st ed.. Trabocchi A. John Wiley & Sons; Hoboken: 2013. 1