Application of a Cross-Metathesis and Intramolecular Aza-Diels–Alder Sequence to the Synthesis of trans-2,3-Disubstituted Tetrahydroquinolines

Abstract

The synthesis of 2,3-disubstituted tetrahydroquinolines has been achieved by first performing a cross-metathesis of different alkenes with readily available N-allyloxycarbonyl-2-chloromethylaniline. Among the catalysts tested, Hoveyda–Grubbs reagent appeared to be the most suitable, reaching the substituted analogues with complete E-stereocontrol and convenient yields. An intramolecular aza-Diels–Alder reaction was further carried out in the presence of potassium phosphate as promoter to deliver the corresponding 2,3-disubstituted tetrahydroquinolines.

Key words

cross-metathesis - azaxylylenes - cycloadditions - Diels–Alder reaction

• References

• 1 Kaur K, Jain M, Reddy RP, Jain R. Eur. J. Med. Chem. 2010; 45: 3245
• 2 Grande F, Garofalo A, Neamati N. Curr. Pharm. Des. 2008; 14: 385
• 3 Jacquemond-Collet I, Benoît-Vical F, Mustofa VA, Stanislas E, Mallie M, Fouraste I. Planta Med. 2002; 68: 68-69
• 4 Aubin N, Barneoud P, Carter C, Caille D, Sontag N, Marc C, Lolivier J, Gardes A, Perron C, Le Kim A, Charieras T, Pandini M, Burnier P, Puech F, Jegham S, George P, Scatton B, Curet O. J. Pharmacol. Exp. Ther. 2004; 310: 1171
• 5 Omura S, Nakagawa A. Tetrahedron Lett. 1981; 22: 2199
• 6 Sridharan V, Suryavanshi PA, Menéndez JC. Chem. Rev. 2011; 111: 7157
• 7 Katritzky AR, Rachwal S, Rachwal B. Tetrahedron 1996; 52: 15031
• 8a Abarca B, Adam R, Ballesteros R. Org. Biomol. Chem. 2012; 10: 1826
• 8b Ren L, Lei T, Ye J.-X, Gong L.-Z. Angew. Chem. Int. Ed. 2012; 51: 771
• 8c Wang T, Zhuo L.-G, Li Z, Chen F, Ding Z, He Y, Fan Q.-H, Xing J, Yu Z.-X, Chan AS. C. J. Am. Chem. Soc. 2011; 133: 9878
• 8d Dobereiner GE, Nova A, Schley ND, Hazari N, Miller SJ, Eisenstein O, Crabtree RH. J. Am. Chem. Soc. 2011; 133: 7547
• 8e Wang D.-W, Wang X.-B, Wang D.-S, Lu S.-M, Zhou Y.-G, Li Y.-X. J. Org. Chem. 2009; 74: 2780
• 8f Fache F. Synlett 2004; 2827
• 9 Wojciechowski K. Eur. J. Org. Chem. 2001; 3587
• 10 Consonni R, Dalla Croce P, Ferraccioli R, La Rosa C. J. Chem. Soc., Perkin Trans. 1 1996; 1809
• 11a Steinhagen H, Corey EJ. Angew. Chem. Int. Ed. 1999; 38: 1928
• 11b Steinhagen H, Corey EJ. Org. Lett. 1999; 1: 823
• 12 Keck D, Vanderheiden S, Bräse S. Eur. J. Org. Chem. 2006; 4916
• 13 Avemaria F, Vanderheiden S, Bräse S. Tetrahedron 2003; 59: 6785
• 14 Mukhina OA, Kumar NN. B, Arisco TM, Valiulin RA, Metzel GA, Kutateladze AG. Angew. Chem. Int. Ed. 2011; 50: 9423
• 15a Fürstner A. Chem. Commun. 2011; 47: 6505
• 15b Kotha S, Dipak MK. Tetrahedron 2011; 68: 397
• 15c Prunet J. Eur. J. Org. Chem. 2011; 3634
• 15d Prunet J, Grimaud L In Metathesis in Natural Product Synthesis . Cossy J, Arseniyadis S, Meyer C. Wiley-VCH; Weinheim: 2010. 287
• 16a Blackwell HE, O’Leary DJ, Chatterjee AK, Washenfelder RA, Bussmann DA, Grubbs RH. J. Am. Chem. Soc. 2000; 122: 58
• 16b Chatterjee AK, Choi T.-L, Sanders DP, Grubbs RH. J. Am. Chem. Soc. 2003; 125: 11360
• 17a Braun M.-G, Vincent A, Boumediene M, Prunet J. J. Org. Chem. 2011; 76: 4921
• 17b Samojlowicz C, Borré E, Mauduit M, Grela K. Adv. Synth. Catal. 2011; 353: 1993
• 18 Meek SJ, O’Brien RV, Llaveria J, Schrock RR, Hoveyda AH. Nature 2011; 471: 461
• 19a Endo K, Grubbs RH. J. Am. Chem. Soc. 2011; 133: 8525
• 19b Keitz BK, Endo K, Herbert MB, Grubbs RH. J. Am. Chem. Soc. 2011; 133: 9686
• 20a Raffier L, Izquierdo F, Piva O. Synthesis 2011; 4037
• 20b Cros F, Pelotier B, Piva O. Synthesis 2010; 233
• 20c Cros F, Ruiz J, Pelotier B, Piva O. Synlett 2010; 2621
• 20d Cros F, Pelotier B, Piva O. Eur. J. Org. Chem. 2010; 5063
• 20e Bourcet E, Fache F, Piva O. Eur. J. Org. Chem. 2010; 4075 ; and references cited therein