Organocatalytic Generation of o-Quinone Methides from Commonly Used o-Hydroxystyrenes at High Temperature for Enantioselective Cyclization

Abstract

o-Quinone methides generated at high temperature under organocatalysis from commonly used o-hydroxystyrenes undergo enantioselective cyclization with dimedone-derived enaminones, to form biologically important tetrahydroxanthenes in high yields and good enantioselectivities (up to 88% yield, 95:5 er). The reaction proceeds in chlorobenzene in the presence of a chiral phosphoric acid (CPA) at 110 °C. The reaction scope with regard to various ring-substituted o-hydro­xy­styrenes and various N-aryl-substituted enaminones was investigated. In addition, this reaction also provided an efficient method for constructing chiral tetrahydroxanthene scaffolds.

Key words

organocatalysis - enantioselectivity - asymmetric synthesis - o-quinone methide - o-hydroxystyrene

• References

• 1 These authors contributed equally to the work.

For substitutions, see:
• 2a Zhang H.-H, Wang Y.-M, Xie Y.-W, Zhu Z.-Q, Shi F, Tu S.-J. J. Org. Chem. 2014; 79: 7141
• 2b Liu Y, Zhang H.-H, Zhang Y.-C, Jiang Y, Shi F, Tu S.-J. Chem. Commun. 2014; 50: 12054

For cycloadditions, see:
• 2c Shi F, Xing G.-J, Tao Z.-L, Luo S.-W, Tu S.-J, Gong L.-Z. J. Org. Chem. 2012; 77: 6970
• 2d Yu S.-Y, Zhang H, Gao Y, Mo L, Wang S, Yao Z.-J. J. Am. Chem. Soc. 2013; 135: 11402
• 2e Shi F, Xing G.-J, Zhu R.-Y, Tan W, Tu S. Org. Lett. 2013; 15: 128
• 2f Zhu R.-Y, Wang C.-S, Zheng J, Shi F, Tu S.-J. J. Org. Chem. 2014; 79: 9305
• 2g Zhang H, Zhu L, Wang S, Yao Z.-J. J. Org. Chem. 2014; 79: 7063
• 3a Wang X, Guram A, Caille S, Hu J, Preston JP, Ronk M, Walker S. Org. Lett. 2011; 13: 1881
• 3b He H, Ye K.-Y, Wu Q.-F, Dai L.-X, You S.-L. Adv. Synth. Catal. 2012; 354: 1084

For a review, see:
• 4a Pathak TP, Sigman MS. J. Org. Chem. 2011; 76: 9210

For some representative examples, see:
• 4b Zhang Y, Sigman MS. J. Am. Chem. Soc. 2007; 129: 3076
• 4c Jensen KH, Pathak TP, Zhang Y, Sigman MS. J. Am. Chem. Soc. 2009; 131: 17074
• 4d Pathak TP, Gligorich KM, Welm BE, Sigman MS. J. Am. Chem. Soc. 2010; 132: 7870
• 5a Wang ZB, Ai FJ, Wang Z, Zhao WX, Zhu GY, Lin ZY, Sun JW. J. Am. Chem. Soc. 2015; 137: 383
• 5b Li M.-L, Chen D.-F, Luo S.-W, Wu X. Tetrahedron: Asymmetry 2015; 26: 219
• 5c Dai W, Lu H, Jiang X.-L, Gao T.-T, Shi F. Tetrahedron: Asymmetry 2015; 26: 109
• 5d Zhang Y.-C, Zhu Q.-N, Yang X, Zhou L.-J, Shi F. J. Org. Chem. 2016; 81: 1681

For some recent reviews containing o-QM-involved catalytic enantioselective reactions, see:
• 6a Wang Z, Sun J. Synthesis 2015; 47: 3629
• 6b Jaworski AA, Scheidt KA. J. Org. Chem. 2016; 81: 10145

For some recent examples of o-QM-involved catalytic enantioselective cyclizations, see:
• 6c Saha S, Schneider C. Chem. Eur. J. 2015; 21: 2348
• 6d Saha S, Schneider C. Org. Lett. 2015; 17: 648
• 6e Hsiao C.-C, Raja S, Liao H.-H, Atodiresei I, Rueping M. Angew. Chem. Int. Ed. 2015; 54: 5762
• 6f Tsui GC, Liu L, List B. Angew. Chem. Int. Ed. 2015; 54: 7703
• 6g Zhao J.-J, Sun S.-B, He S.-H, Wu Q, Shi F. Angew. Chem. Int. Ed. 2015; 54: 5460
• 6h Zhao J.-J, Zhang Y.-C, Xu M.-M, Tang M, Shi F. J. Org. Chem. 2015; 80: 10016

For some reviews, see:
• 7a Akiyama T. Chem. Rev. 2007; 107: 5744
• 7b Terada M. Chem. Commun. 2008; 35: 4097
• 7c Terada M. Synthesis 2010; 1929
• 7d Yu J, Shi F, Gong L.-Z. Acc. Chem. Res. 2011; 44: 1156
• 7e Parmar D, Sugiono E, Raja S, Rueping M. Chem. Rev. 2014; 114: 9047
• 7f Wu H, He Y.-P, Shi F. Synthesis 2015; 47: 1990
• 8a Zhang Y.-C, Zhao J.-J, Jiang F, Sun S.-B, Shi F. Angew. Chem. Int. Ed. 2014; 53: 13912
• 8b Wang Y.-M, Zhang H.-H, Li C, Fan T, Shi F. Chem. Commun. 2016; 52: 1804
• 8c Sun X.-X, Zhang H.-H, Li G.-H, Meng L, Shi F. Chem. Commun. 2016; 52: 2968
• 8d Wu Q, Ma C, Du X.-H, Chen Y, Cai P.-J. Synthesis 2016; 48: 595
• 8e Liang J, Zhang H.-H, Wang C.-S, Wu Q, Shi F. Synthesis 2016; 48: 4548
• 9a Hafez HN, Hegab MI, Ahmed-Farag IS, El-Gazzar AB. A. Bioorg. Med. Chem. Lett. 2008; 18: 4538
• 9b Poupelin JP, Saint-Ruf G, Foussard-Blanpin O, Marcisse G, Uchida-Earnauf G, Lacroix R. Eur. J. Med. Chem. 1978; 13: 67
• 10 Lan Y.-B, Zhao H, Liu Z.-M, Liu G.-G, Tao J.-C, Wang X.-W. Org. Lett. 2011; 13: 4866