Synlett, Inhaltsverzeichnis Synlett 2013; 24(1): 117-119DOI: 10.1055/s-0032-1317859 letter © Georg Thieme Verlag Stuttgart · New York Variations in Site of Lithiation of N-[2-(4-Methoxyphenyl)ethyl]pivalamide – Use in Ring Substitution Keith Smith* , Gamal A. El-Hiti* , Mohammed B. Alshammari Artikel empfehlen Abstract Alle Artikel dieser Rubrik Abstract Lithiation of N-[2-(4-methoxyphenyl)ethyl]pivalamide at –20 to 0 °C with three equivalents of n-BuLi in anhydrous THF, followed by reactions with various electrophiles, gives high yields of products involving ring substitution ortho to the pivaloylaminoethyl group, which was unexpected in view of earlier results reported with t-BuLi. Key words Key words N-[2-(4-methoxyphenyl)ethyl]pivalamide - directed lithiation - synthesis - electrophile - dilithium intermediate Volltext Referenzen References and Notes 1 Permanent address: G. A. El-Hiti, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt. See, for example: 2a Clayden J. Organolithiums: Selectivity for Synthesis. Pergamon; Oxford: 2002 2b Schlosser M. Organometallics in Synthesis . 2nd ed. Wiley; Chichester: 2002: 1-352 2c Capriati V, Florio S, Salomone A. Top. Stereochem. 2010; 26: 135 2d Coldham I, Sheikh NS. Top. Stereochem. 2010; 26: 253 See, for example: 3a Beak P, Snieckus V. Acc. Chem. Res. 1982; 15: 306 3b Nájera C, Sansano JM, Yus M. Tetrahedron 2003; 59: 9255 3c Whisler MC, MacNeil S, Snieckus V, Beak P. Angew. Chem. Int. Ed. 2004; 43: 2206 3d Chadwick ST, Ramirez A, Gupta L, Collum DB. J. Am. Chem. Soc. 2007; 129: 2259 3e Dyke AM, Gill DM, Harvey JN, Hester AJ, Lloyd-Jones GC, Muñoz MP, Shepperson IR. Angew. Chem. Int. Ed. 2008; 47: 5067 3f Coldham I, Raimbault S, Chovatia PT, Patel JJ, Leonori D, Sheikh NS, Whittaker DT. E. Chem. Commun. 2008; 4174 3g Coldham I, Leonori D, Beng TK, Gawley RE. Chem. Commun. 2009; 5239 3h Coldham I, Raimbault S, Whittaker DT. E, Chovatia PT, Leonori D, Patel JJ, Sheikh NS. Chem. Eur. J. 2010; 16: 4082 3i Robinson SP, Sheikh NS, Baxter Carl A, Coldham I. Tetrahedron Lett. 2010; 51: 3642 3j Guerrand HD. S, Adams H, Coldham I. Org. Biomol. Chem. 2011; 9: 7921 3k Thompson MJ, Louth JC, Little SM, Jackson MP, Boursereau Y, Chen B, Coldham I. ChemMedChem 2012; 7: 578 3l Sheikh NS, Leonori D, Barker G, Firth JD, Campos KR, Meijer AJ. H. M, O’Brien P, Coldham I. J. Am. Chem. Soc. 2012; 134: 5300 See, for example: 4a Beak P, Zajdel WJ, Reitz DB. Chem. Rev. 1984; 84: 471 4b Snieckus V. Chem. Rev. 1990; 90: 879 4c El-Hiti GA. Heterocycles 2000; 53: 1839 4d Turck A, Plé N, Mongin F, Quéguiner G. Tetrahedron 2001; 57: 4489 4e Anctil EJ.-G, Snieckus V. J. Organomet. Chem. 2002; 653: 150 4f Smith K, El-Hiti GA. Curr. Org. Synth. 2004; 1: 253 4g Chinchilla R, Nájera C, Yus M. Chem. Rev. 2004; 104: 2667 4h Schlosser M. Angew. Chem. Int. Ed. 2005; 44: 376 4i Foubelo F, Yus M. Curr. Org. Chem. 2005; 9: 459 4j Rathman TL, Bailey WF. Org. Process Res. Dev. 2009; 13: 144 4k Houlden CE, Lloyd-Jones GC, Booker-Milburn KI. Org. Lett. 2010; 12: 3090 4l Page A, Clayden J. Beilstein J. Org. Chem. 2011; 7: 1327 4m El-Hiti GA, Hegazy AS, Alotaibi MH, Ajarim MD. ARKIVOC 2012; (vii): 35 Examples for substituted benzenes: 5a Clayden J, Turner H, Pickworth M, Adler T. Org. Lett. 2005; 7: 3147 5b Clayden J, Dufour J. Tetrahedron Lett. 2006; 47: 6945 5c Burgos PO, Fernández I, Iglesias MJ, García-Granda S, Ortiz FL. Org. Lett. 2008; 10: 537 5d Castanet A.-S, Tilly D, Véron J.-B, Samanta SS, De A, Ganguly T, Mortier J. Tetrahedron 2008; 64: 3331 5e Michon C, Murai M, Nakatsu M, Uenishi J, Uemura M. Tetrahedron 2009; 65: 752 5f Tilly D, Fu J.-M, Zhao B.-P, Alessi M, Catanet A.-S, Snieckus V, Mortier J. Org. Lett. 2010; 12: 68 5g Slocum DW, Wang S, White CB, Whitley PE. Tetrahedron 2010; 66: 4939 5h Cho I, Meimetis L, Belding L, Katz MJ, Dudding T, Britton R. Beilstein J. Org. Chem. 2011; 7: 1315 5i Schmid M, Waldner B, Schnürch M, Mihovilovic MD, Stanetty P. Tetrahedron 2011; 67: 2895 5j Volz N, Clayden J. Angew. Chem. Int. Ed. 2011; 50: 12148 Examples for substituted heterocycles: 6a Robert N, Bonneau A.-L, Hoarau C, Marsais F. Org. Lett. 2006; 8: 6071 6b Comoy C, Banaszak E, Fort Y. Tetrahedron 2006; 62: 6036 6c Luisi R, Capriati V, Florio S, Musio B. Org. Lett. 2007; 9: 1263 6d Clayden J, Hennecke U. Org. Lett. 2008; 10: 3567 6e McLaughlin M, Marcantonio K, Chen C, Davies IW. J. Org. Chem. 2008; 73: 4309 6f Capriati V, Florio S, Luisi R, Mazzanti A, Musio B. J. Org. Chem. 2008; 73: 3197 6g Affortunato F, Florio S, Luisi R, Musio B. J. Org. Chem. 2008; 73: 9214 6h Musio B, Clarkson GJ, Shipman M, Florio S, Luisi R. Org. Lett. 2009; 11: 325 6i Clayton J, Clayden J. Tetrahedron Lett. 2011; 52: 2436 6j Ibrahim N, Chevot F, Legraverend M. Tetrahedron Lett. 2011; 52: 305 See, for example: 7a Smith K, El-Hiti GA, Abdo MA, Abdel-Megeed MF. J. Chem. Soc., Perkin Trans. 1 1995; 1029 7b Smith K, El-Hiti GA, Abdel-Megeed MF, Abdo MA. J. Org. Chem. 1996; 61: 647 7c Smith K, El-Hiti GA, Abdel-Megeed MF, Abdo MA. J. Org. Chem. 1996; 61: 656 7d Smith K, El-Hiti GA, Pritchard GJ, Hamilton A. J. Chem. Soc., Perkin Trans. 1 1999; 2299 7e Smith K, El-Hiti GA, Shukla AP. J. Chem. Soc., Perkin Trans. 1 1999; 2305 7f Smith K, El-Hiti GA, Hawes AC. Synthesis 2003; 2047 7g Smith K, El-Hiti GA, Mahgoub SA. Synthesis 2003; 2345 7h El-Hiti GA. Synthesis 2003; 2799 7i Smith K, El-Hiti GA, Abdel-Megeed MF. Synthesis 2004; 2121 7j El-Hiti GA. Synthesis 2004; 363 7k Smith K, El-Hiti GA, Hegazy AS. Synthesis 2005; 2951 7l Smith K, Barratt ML. J. Org. Chem. 2007; 72: 1031 8a Smith K, El-Hiti GA, Hegazy AS. Synlett 2009; 2242 8b Smith K, El-Hiti GA, Hegazy AS, Fekri A, Kariuki BM. ARKIVOC 2009; (xiv): 266 9a Smith K, El-Hiti GA, Hegazy AS. Chem. Commun. 2010; 46: 2790 9b Smith K, El-Hiti GA, Hegazy AS, Fekri A. Heterocycles 2010; 80: 941 9c Smith K, El-Hiti GA, Hegazy AS. Synthesis 2010; 1371 9d Smith K, El-Hiti GA, Hegazy AS, Kariuki B. Beilstein J. Org. Chem. 2011; 7: 1219 10 Simig G, Schlosser M. Tetrahedron Lett. 1988; 29: 4277 11 Smith K, El-Hiti GA, Alshammari MB. Synthesis 2012; 44: 2013 12 Simig G, Schlosser M. Tetrahedron Lett. 1991; 32: 1963 13 Assignments of signals are based on integration values, coupling patterns, and expected chemical shifts and have not been rigorously confirmed. Signals with similar characteristics might be interchanged. 14 Analytical Data for 7 White solid (0.32 g, 92%); mp 179–181 °C. FTIR: νmax = 3321, 2958, 1627, 1575, 1292, 1243 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.35–7.26 (m, 11 H, OH and 2 C6H5), 7.16 (d, J = 8.3 Hz, 1 H, H-6 of 4-MeOC6H3), 6.79 (dd, J = 2.8, 8.3 Hz, 1 H, H-5 of 4-MeOC6H3), 6.24 (d, J = 2.8 Hz, 1 H, H-3 of 4-MeOC6H3), 6.15 (br, exch., 1 H, NH), 3.63 (s, 3 H, OCH3), 3.37 (app q, J = 7 Hz, 2 H, CH2 NH), 2.60 (t, J = 7.2 Hz, 2 H, CH2), 1.11 [s, 9 H, C(CH3)3] ppm. 13C NMR (125 MHz, CDCl3): δ = 178.8 (s, C=O), 156.9 (s, C-4 of 4-MeOC6H3), 147.1 (s, C-1 of 2 C6H5), 146.6 (s, C-2 of 4-MeOC6H3), 132.8 (d, C-6 of 4-MeOC6H3), 130.7 (s, C-1 of 4-MeOC6H3), 127.9 (d, C-3/C-5 of 2 C6H5), 127.7 (d, C-2/C-6 of 2 C6H5), 127.2 (d, C-4 of 2 C6H5), 117.1 (d, C-3 of 4-MeOC6H3), 111.9 (d, C-5 of 4-MeOC6H3), 83.0 (s, COH), 55.0 (q, OCH3), 41.1 (t, CH2NH), 38.4 [s, C(CH3)3], 32.5 (t, ArCH2), 27.5 [q, C(CH3)3] ppm. MS (EI): m/z (%) = 399 (77) [M – H2O]+, 298 (99), 285 (90), 261 (33), 239 (10), 222 (26), 209 (31), 193 (73), 165 (53), 152 (13), 105 (48), 83 (100). HRMS (EI): m/z calcd for C27H29NO2 [M – H2O]+: 399.2198; found: 399.2187.
