Base-Mediated Tandem 1,6-Addition/Cyclization/Isomerization Reactions between para-Quinone Methides and Benzyl Chlorides: Approaches to Diverse Frameworks at Each Cascade Stage

Abstract

Base-mediated stereospecific tandem reactions using para-quinone methides and carbene-like benzyl chlorides are developed. DBU-mediated 1,6-addition/cyclization/isomerization reactions produce triarylsubstituted alkenes in 43–89% yields and Z/E ratios of 5:1 to 35:1 in favor of the Z-isomers. Single-step 1,6-conjugate additions are realized with the mediation of cesium carbonate, and different triaryl chloroethanes are obtained in yields of 41–54% and excellent diastereoselectivities of more than 20:1. In addition, tandem 1,6-addition/cyclization reactions are achieved using tuned 2,4-disubstituted benzyl chlorides to afford diaryl spirocyclopropyl para-dienones in yields of 35–83% and diastereoselectivities of more than 20:1 in favor of the anti-isomers. The transformations from triaryl chloroethanes and spirocyclopropyl para-dienones into triarylsubstituted alkenes are also demonstrated to support the proposed tandem mechanisms.

Key words

benzyl chlorides - para-quinone methides - tandem reactions - triarylsubstituted alkenes - spirocyclopropyl para-dienones

• References

• 1a Schneider TF, Kaschel J, Werz DB. Angew. Chem. Int. Ed. 2014; 53: 5504
• 1b Brackmann F, de Meijere A. Chem. Rev. 2007; 107: 4493
• 1c Reissig H.-U, Zimmer R. Chem. Rev. 2003; 103: 1151
• 1d Tanasova M, Sturla SJ. Chem. Rev. 2012; 112: 3578
• 1e Wessjohann LA, Brandt W, Thiemann T. Chem. Rev. 2003; 103: 1625
• 1f Wong HN. C, Hon MY, Tse CW, Yip YC, Tanko J, Hudlicky T. Chem. Rev. 1989; 89: 165
• 1g Cavitt MA, Phun LH, France S. Chem. Soc. Rev. 2014; 43: 804
• 1h Chen DY. K, Pouwer RH, Richard J.-A. Chem. Soc. Rev. 2012; 41: 4631
• 1i Grover HK, Emmett MR, Kerr MA. Org. Biomol. Chem. 2015; 13: 655
• 1j Budynina EM, Ivanov KL, Sorokin ID, Melnikov MY. Synthesis 2017; 49: 3035
• 2a Hurley LH, Lee CS, McGovren JP, Warpehoski MA, Mitchell MA, Kelly RC, Aristoff PA. Biochemistry 1988; 27: 3886
• 2b Boger DL, Boyce CW, Garbaccio RM, Goldberg JA. Chem. Rev. 1997; 97: 787
• 2c MacMillan KS, Boger DL. J. Med. Chem. 2009; 52: 5771
• 2d Boger DL, Ishizaki T, Zarrinmayeh H, Munk SA, Kitos PA, Suntornwat O. J. Am. Chem. Soc. 1990; 112: 8961
• 2e Parrish JP, Kastrinsky DB, Wolkenberg SE, Igarashi Y, Boger DL. J. Am. Chem. Soc. 2003; 125: 10971
• 2f Schnell JR, Ketchem RR, Boger DL, Chazin WJ. J. Am. Chem. Soc. 1999; 121: 5645
• 3a Dao HT, Baran PS. Angew. Chem. Int. Ed. 2014; 53: 14382
• 3b Becker HD, Elebring T. J. Org. Chem. 1985; 50: 1319
• 3c Field KW, Schuster GB. J. Org. Chem. 1988; 53: 4000
• 3d Koser GF, Pirkle WH. J. Org. Chem. 1967; 32: 1992
• 3e Ohno T, Martín N, Knight B, Wudl F, Suzuki T, Yu H. J. Org. Chem. 1996; 61: 1306
• 4a Gai K, Fang X, Li X, Xu J, Wu X, Lin A, Yao H. Chem. Commun. 2015; 51: 15831
• 4b Yuan Z, Fang X, Li X, Wu J, Yao H, Lin A. J. Org. Chem. 2015; 80: 11123
• 4c Zhang XZ, Du JY, Deng YH, Chu WD, Yan X, Yu KY, Fan CA. J. Org. Chem. 2016; 81: 2598
• 4d Roiser L, Waser M. Org. Lett. 2017; 19: 2338
• 5a Chauhan P, Kaya U, Enders D. Adv. Synth. Cat. 2017; 359: 888
• 5b Toteva MM, Richard JP. In Advances in Physical Organic Chemistry, Vol. 45. Richard JP. Academic Press; New York: 2011: 39-91
• 5c Peter MG. Angew. Chem., Int. Ed. Engl. 1989; 28: 555
• 5d Parra A, Tortosa M. ChemCatChem 2015; 7: 1524
• 5e Caruana L, Fochi M, Bernardi L. Molecules 2015; 20: 11733
• 5f Turner AB. Q. Rev. Chem. Soc. 1964; 18: 347
• 6a Kopinke F.-D, Zimmermann G, Aust J, Scherzer K. Chem. Ber. 1989; 122: 721
• 6b Lifshitz A, Tamburu C, Dubnikova F. J. Phys. Chem. A 2009; 113: 10446
• 6c Chambers TS, Kistiakowsky GB. J. Am. Chem. Soc. 1934; 56: 399
• 7a Hixson SS, Franke LA. J. Org. Chem. 1988; 53: 2706
• 7b Mizuno K, Ichinose N, Otsuji Y. J. Am. Chem. Soc. 1985; 107: 5797
• 7c Zimmerman HE, Kamath AP. J. Am. Chem. Soc. 1988; 110: 900
• 8 Rubin M, Rubina M, Gevorgyan V. Chem. Rev. 2007; 107: 3117
• 9a Chagarovskiy AO, Ivanova OA, Rakhmankulov ER, Budynina EM, Trushkov IV, Melnikov MY. Adv. Synth. Cat. 2010; 352: 3179
• 9b Zhang Z.-Y, Liu Z.-Y, Guo R.-T, Zhao Y.-Q, Li X, Wang X.-C. Angew. Chem. Int. Ed. 2017; 56: 4028
• 9c Selvi T, Srinivasan K. J. Org. Chem. 2014; 79: 3653
• 9d Xie H, Zu L, Li H, Wang J, Wang W. J. Am. Chem. Soc. 2007; 129: 10886
• 10a Groszek G, Błażej S, Brud A, Świerczyński D, Lemek T. Tetrahedron 2006; 62: 2622
• 10b Huang B, Shen Y, Mao Z, Liu Y, Cui S. Org. Lett. 2016; 18: 4888
• 11 Song X, Song A, Zhang F, Li H.-X, Wang W. Nat. Commun. 2011; 2: 524
• 12a Chen X, Yu Y, Liao Z, Li H, Wang W. Tetrahedron Lett. 2016; 57: 5742
• 12b Meazza M, Ashe M, Shin HY, Yang HS, Mazzanti A, Yang JW, Rios R. J. Org. Chem. 2016; 81: 3488
• 13 Zhu Y, Zhao S, Zhang M, Song X, Chang J. Synthesis 2019; 51: 899
• 14 CCDC 1877771 (4aa), 1877772 (4ak) and 1877773 (5bk) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.