Practical and Efficient Synthesis of Polyaryl(hetaryl)-Substituted Cyclohexenones and Salicylates

Abstract

A new efficient method was developed for the synthesis of triaryl-substituted cyclohexenones and salicylates. The method is based on the Robinson annulation of readily available keto esters and chalcones, followed by the aromatization of the cyclohexenone moiety. The aromatization can be accomplished either by reaction with bromine in boiling chloroform or bromination with copper(II) bromide in ethanol followed by treatment with pyridine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The new synthetic method was also implemented in a one-pot protocol, which in some cases resulted in higher yields of the final product compared to those obtained in the stepwise synthesis.

Key words

cyclohexenones - salicylates - polyaryl-substituted phenols - Robinson annulation - chalcones - bromination

• References

• 1 Modern Arene Chemistry . Astruc D. Wiley-VCH; Weinheim: 2002
• 2a Tyman JH. P. Synthetic and Natural Phenols . Elsevier; New York: 1996
• 2b Fiegel H, Voges HW, Hamamoto T, Umemura S, Iwata T, Miki H, Fujita Y, Buysch HJ, Garbe D, Paulus W. Phenol Derivatives. Ullmann’s Encyclopedia of Industrial Chemistry . Wiley-VCH; New York: 2002
• 2c The Chemistry of Phenols . Rappoport Z. John Wiley & Sons; New York: 2003
• 3a Hannah J, Ruyle WV, Jones H, Matzuk AR, Kelly KW, Witzel BE, Holtz WJ, Houser RA, Shen TY, Sarett LH. J. Med. Chem. 1978; 21: 1093
• 3b Jones H, Fordice MW, Greenwald RB, Hannah J, Jacobs A, Ruyle WV, Walford GL, Shen TY. J. Med. Chem. 1978; 21: 1100
• 4a Chardonnens L, Hammer W. Helv. Chim. Acta 1968; 51: 2044
• 4b Garcia-Raso A, Garcia-Raso J, Campaner B, Mestres R, Sinisterra JV. Synthesis 1982; 1037
• 4c Eichinger K, Nussbaumer P, Balkan S, Schulz G. Synthesis 1987; 1061
• 4d Hauser FM, Pogany SA. Synthesis 1980; 814
• 4e Yang X, Wang J, Li P. Org. Biomol. Chem. 2014; 12: 2499
• 4f Miesch M, Mislin G, Franck-Neumann M. Tetrahedron Lett. 1998; 39: 6873
• 4g Halland N, Aburel PS, Jørgensen KA. Angew. Chem. Int. Ed. 2004; 43: 1272
• 4h Yi W.-B, Huang X, Caia C, Zhang W. Green Chem. 2012; 14: 3185
• 4i Akiyama T, Katoh T, Mori K. Angew. Chem. Int. Ed. 2009; 48: 4226
• 5 Ivanov C, Tcholakova T. Synthesis 1981; 392
• 6a Duhamel P, Hennequin L, Poirier JM, Tavel G, Vottero C. Tetrahedron 1986; 42: 4777
• 6b Taniguchi K, Tsubaki K, Take K, Okumura K, Terai T, Shiokawa Y. Chem. Pharm. Bull. 1994; 42: 896
• 6c Sato T, Wakahara Y, Otera J, Nozaki H. Tetrahedron Lett. 1990; 31: 1581
• 7 Robl JA. Tetrahedron Lett. 1990; 31: 3421
• 8 Yoshida K, Narui R, Imamoto T. Chem. Eur. J. 2008; 14: 9706
• 9a Kotnis AS. Tetrahedron Lett. 1991; 32: 3441
• 9b Pun D, Diao T, Stahl SS. J. Am. Chem. Soc. 2013; 135: 8213
• 10 Campbell E, Martin JJ, Bordner J, Kleinman EF. J. Org. Chem. 1996; 61: 4806
• 11 Qian J, Yi W, Huang X, Miao Y, Zhang J, Cai C, Zhang W. Org. Lett. 2015; 17: 1090
• 12a Lvov AG, Shirinian VZ, Kachala VV, Kavun AM, Zavarzin IV, Krayushkin MM. Org. Lett. 2014; 16: 4532
• 12b Lvov AG, Shirinian VZ, Zakharov AV, Krayushkin MM, Kachala VV, Zavarzin IV. J. Org. Chem. 2015; 80: 11491
• 13 Shimkin AA, Shirinian VZ, Mailian AK, Lonshakov DV, Gorokhov VV, Krayushkin MM. Russ. Chem. Bull. 2011; 60: 139
• 14 Brown EV, Blanchette JA. J. Am. Chem. Soc. 1950; 72: 3414
• 15a Paul JH, Silverman R, Schwartz LH. Org. Prep. Proced. Int. 1975; 7: 149
• 15b Aoyama T, Takido T, Kodomari M. Tetrahedron Lett. 2004; 45: 1873
• 16 Shirinian VZ, Lonshakov DV, Kachala VV, Zavarzin IV, Shimkin AA, Lvov AG, Krayushkin MM. J. Org. Chem. 2012; 77: 8112
• 17 CCDC 1498904 contains 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.
• 18 Park DY, Kim SJ, Kim TH, Kim JN. Tetrahedron Lett. 2006; 47: 6315
• 19 Shirinian VZ, Lvov AG, Krayushkin MM, Lubuzh ED, Nabatov BV. J. Org. Chem. 2014; 79: 3440