Diels–Alder Reactions of γ-Hydroxybutenolides: Approach to the Himbacine Tricyclic Core

Abstract

The Diels–Alder reaction of γ-hydroxybutenolides with dienes gave good yields of cycloadducts under thermal and Lewis acid catalyzed conditions. The application of this methodology to a more complex system was demonstrated by the synthesis of a model system for the tricyclic himbacine core. The stereo- and regioselective Diels–Alder reaction established three of the stereogenic centers, with the fourth stereogenic center secured by diastereoselective alkylation of the cycloadduct.

Key words

γ-hydroxybutenolide - Diels–Alder reaction - himbacine - Lewis acid catalysis - isomerization

• References

• 1 Nicolaou KC, Snyder SA, Montagnon T, Vassilikogiannakis G. Angew. Chem. Int. Ed. 2002; 41: 1668
• 2a Miles WH, Cohen EM, Naimoli BJ. Synth. Commun. 2013; 43: 1980 ; and references cited therein
• 2b Mukherjee S, Corey EJ. Org. Lett. 2010; 12: 1024
• 2c Kakushima M, Scott DG. Can. J. Chem. 1979; 57: 1399
• 2d Danishefsky S, Prisbylla MP, Hiner S. J. Am. Chem. Soc. 1978; 100: 2918
• 3a Kowalski CJ, Lal GS. J. Am. Chem. Soc. 1988; 110: 3693
• 3b Zhang YD, Tang YF, Luo TP, Shen J, Chen JH, Yang Z. Org. Lett. 2006; 8: 107
• 3c Hu QY, Zhou G, Corey EJ. J. Am. Chem. Soc. 2004; 126: 13708
• 4 Feringa BL, De Lange B, Jansen JF. G. A, De Jong JC, Lubben M, Faber W, Schudde EP. Pure Appl. Chem. 1992; 64: 1865
• 5 Simple γ-alkyl-γ-hydroxybutenolides are at slow exchange in the ¹H NMR at ambient temperature, with the presence of the chain tautomer as high as 5%
• 6 For a review of the synthetic applications of γ-hydroxybutenolides, see: Miles WH. Curr. Org. Synth. 2014; 11: 244
• 7a Miller KK, Zhang P, Nishizawa-Brennen Y, Frost JW. ACS Sustain. Chem. Eng. 2014; 2: 2053
• 7b Furuta K, Miwa Y, Iwanaga K, Yamamoto H. J. Am. Chem. Soc. 1988; 110: 6254
• 7c Al-Zoubi RM, Marion O, Hall DG. Angew. Chem. Int. Ed. 2008; 47: 2876
• 7d Zheng HC, Hall DG. Tetrahedron Lett. 2010; 51: 3561
• 7e Ryu DH, Corey EJ. J. Am. Chem. Soc. 2003; 125: 6388
• 8a Magnus P, Cairns PM. J. Am. Chem. Soc. 1986; 108: 217
• 8b Magnus P, Cairns PM, Moursounidis J. J. Am. Chem. Soc. 1987; 109: 2469
• 9a Noutsias D, Vassilikogiannakis G. Org. Lett. 2012; 14: 3565
• 9b Tu NP. W, Yip JC, Dibble PW. Synthesis 1996; 77
• 9c Sánchez-Obregón R, Salmón M, Walls F. Bol. Inst. Quim. Univ. Nacl. Autón. Méx. 1970; 22: 16 ; Chem. Abstr. 1971, 74, 140602
• 10a Lee GC. M, Syage ET, Harcourt DA, Holmes JM, Garst ME. J. Org. Chem. 1991; 56: 7007
• 10b Adam W, Rodriguez A. Tetrahedron Lett. 1981; 22: 3505
• 10c Feringa BL. Recl. Trav. Chim. Pays-Bas 1987; 106: 469
• 10d Cottier L, Descotes G, Eymard L, Rapp K. Synthesis 1995; 303
• 10e Annangudi SP, Sun MJ, Salomon RG. Synlett 2005; 1468
• 11a Larson RT, Pemberton RP, Franke JM, Tantillo DJ, Thomson RJ. J. Am. Chem. Soc. 2015; 137: 11197
• 11b Chackalamannil S, Wang YG, Greenlee WJ, Hu ZY, Xia Y, Ahn HS, Boykow G, Hsieh YS, Palamanda J, Agans-Fantuzzi J, Kurowski S, Graziano M, Chintala M. J. Med. Chem. 2008; 51: 3061
• 12 Liu P, Pan YM, Hu K, Huang XC, Liang Y, Wang HS. Tetrahedron 2013; 69: 7925
• 13 Miles WH, Duca DG, Selfridge BR, De Sousa CA. P, Harriman KB, Goodzeit EO, Freedman JT. Tetrahedron Lett. 2007; 48: 7809
• 14 In some cases, broadening of the peaks in the NMR spectra of these cycloadducts may be attributable to hydrogen bonding; see: Klika KD, Tahtinen P, Dahlqvist M, Szabo JA, Stajer G, Sinkkonen J, Pihlaja K. J. Chem. Soc., Perkin Trans. 2 2000; 687

For representative examples of isomerization of [2.2.1]-bicyclic systems, see:
• 15a Suzuki J, Harada T. Synthesis 2006; 2483
• 15b Miklos F, Sohar P, Csampai A, Sillanpaa R, Peter M, Stajer G. Heterocycles 2002; 57: 2309
• 15c Rajsfus DE, Alter-Zilberfarb S, Frimer AA. J. Fluorine Chem. 2013; 148: 49
• 16 With the unequivocal synthesis of 3a and these isomerization studies, the lack of certainty about the assignment of the stereochemistry of compound ‘4’ in Pinnick’s paper is clarified.¹⁷ In Pinnick’s study, the addition of lithium dimethylcuprate to endo-Diels–Alder product of cyclopentadiene and maleic anhydride gave a product whose NMR spectra match the spectra of 12a, and not 3a. A similar study by Walton, in which cadmium reagents were added to above endo-Diels–Alder product, appears to lead to isomerization since the melting points of both 3a and 3b differ considerably from the values given in the paper but are very close to the melting points found for isomerized compounds 12a and 12b.¹⁸ A study of the addition of some Grignard reagents to anhydrides has previously been noted to cause isomerization of the resulting keto acids.¹⁹ The nickel-catalyzed reactions of zinc reagents to anhydrides, on the other hand, appears to occur without isomerization, since the product from the above endo-Diels–Alder product exhibited a complex ¹H NMR spectra due to ‘rotomers,’ that is, ring and chain tautomers.²⁰
• 17 Cornelius LA. M, Bone RG. A, Hastings RH, Deardorff MA, Scharlach RA, Hauptmann BE, Stankovic CS, Pinnick HW. J. Org. Chem. 1993; 58: 3188
• 18 Walton HM. J. Org. Chem. 1957; 22: 312
• 19 Canonne P, Plamondon J, Akssira M. Tetrahedron 1988; 44: 2903
• 20 Bercot EA, Rovis T. J. Am. Chem. Soc. 2002; 124: 174
• 21 Rinner U, Lentsch C, Aichinger C. Synthesis 2010; 3763
• 22 Chackalamannil S, Wang YG, Greenlee WJ, Hu ZY, Xia Y, Ahn HS, Boykow G, Hsieh YS, Palamanda J, Agans-Fantuzzi J, Kurowski S, Graziano M, Chintala M. J. Med. Chem. 2008; 51: 3061
• 23 Gao LJ, Waelbroeck M, Hofman S, Van Haver D, Milanesio M, Viterbo D, De Clercq PJ. Bioorg. Med. Chem. Lett. 2002; 12: 1909
• 24 Doller D, Chackalamannil S, Czarniecki M, McQuade R, Ruperto V. Bioorg. Med. Chem. Lett. 1999; 9: 901
• 25 Larson RT, Pemberton RP, Franke JM, Tantillo DJ, Thomson RJ. J. Am. Chem. Soc. 2015; 137: 11197
• 26 Howell JM, Liu W, Young AJ, White MC. J. Am. Chem. Soc. 2006; 136: 5750
• 27 Takadoi M, Katoh T, Ishiwata A, Terashima S. Tetrahedron 2002; 58: 9903
• 28 Takadoi M, Yamaguchi K, Terashima S. Bioorg. Med. Chem. 2003; 11: 1169
• 29 Bercot EA, Kindrachuk DE, Rovis T. Org. Lett. 2005; 7: 107
• 30a Shi H, Liu H, Bloch R, Mandville GR. Tetrahedron 2001; 57: 9335
• 30b Frenette R, Monette M, Bernstein MA, Young RN, Verhoeven TR. J. Org. Chem. 1991; 56: 3083
• 31 APEX2 . Bruker AXS Inc; Madison (WI, USA): 2009
• 32 Sheldrick GM. SADABS . University of Gottingen; Germany: 2008
• 33 Sheldrick GM. Acta Crystallogr., Sect. A 2008; 64: 112
• 34 Allen FH, Johnson O, Shields GP, Smith BR, Towler M. J. Appl. Crystallogr. 2004; 37: 335
• 35 Cycloadduct 9e has been previously reported, but likely to be the trans-compound: Andreev VM, Usova AV. Bull. Acad. Sci. USSR, Div. Chem. Sci. 1966; 15: 1351