Variations in Site of Lithiation of N-[2-(4-Methoxyphenyl)ethyl]pivalamide – Use in Ring Substitution

 

 Lizenzen und Reprints 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.

• 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
  Suche in Google Scholar
• 2b Schlosser M. Organometallics in Synthesis . 2nd ed. Wiley; Chichester: 2002: 1-352
  Suche in Google Scholar
• 2c Capriati V, Florio S, Salomone A. Top. Stereochem. 2010; 26: 135
  Suche in Google Scholar
• 2d Coldham I, Sheikh NS. Top. Stereochem. 2010; 26: 253
  Suche in Google Scholar

See, for example:
• 3a Beak P, Snieckus V. Acc. Chem. Res. 1982; 15: 306
  CrossrefSuche in Google Scholar
• 3b Nájera C, Sansano JM, Yus M. Tetrahedron 2003; 59: 9255
  CrossrefSuche in Google Scholar
• 3c Whisler MC, MacNeil S, Snieckus V, Beak P. Angew. Chem. Int. Ed. 2004; 43: 2206
  CrossrefPubMedSuche in Google Scholar
• 3d Chadwick ST, Ramirez A, Gupta L, Collum DB. J. Am. Chem. Soc. 2007; 129: 2259
  CrossrefSuche in Google Scholar
• 3e Dyke AM, Gill DM, Harvey JN, Hester AJ, Lloyd-Jones GC, Muñoz MP, Shepperson IR. Angew. Chem. Int. Ed. 2008; 47: 5067
  CrossrefSuche in Google Scholar
• 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
  CrossrefSuche in Google Scholar
• 3i Robinson SP, Sheikh NS, Baxter Carl A, Coldham I. Tetrahedron Lett. 2010; 51: 3642
  CrossrefSuche in Google Scholar
• 3j Guerrand HD. S, Adams H, Coldham I. Org. Biomol. Chem. 2011; 9: 7921
  CrossrefPubMedSuche in Google Scholar
• 3k Thompson MJ, Louth JC, Little SM, Jackson MP, Boursereau Y, Chen B, Coldham I. ChemMedChem 2012; 7: 578
  Suche in Google Scholar
• 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
  CrossrefSuche in Google Scholar

See, for example:
• 4a Beak P, Zajdel WJ, Reitz DB. Chem. Rev. 1984; 84: 471
  CrossrefSuche in Google Scholar
• 4b Snieckus V. Chem. Rev. 1990; 90: 879
  Suche in Google Scholar
• 4c El-Hiti GA. Heterocycles 2000; 53: 1839
  CrossrefSuche in Google Scholar
• 4d Turck A, Plé N, Mongin F, Quéguiner G. Tetrahedron 2001; 57: 4489
  CrossrefSuche in Google Scholar
• 4e Anctil EJ.-G, Snieckus V. J. Organomet. Chem. 2002; 653: 150
  CrossrefSuche in Google Scholar
• 4f Smith K, El-Hiti GA. Curr. Org. Synth. 2004; 1: 253
  CrossrefSuche in Google Scholar
• 4g Chinchilla R, Nájera C, Yus M. Chem. Rev. 2004; 104: 2667
  CrossrefPubMedSuche in Google Scholar
• 4h Schlosser M. Angew. Chem. Int. Ed. 2005; 44: 376
  CrossrefSuche in Google Scholar
• 4i Foubelo F, Yus M. Curr. Org. Chem. 2005; 9: 459
  CrossrefSuche in Google Scholar
• 4j Rathman TL, Bailey WF. Org. Process Res. Dev. 2009; 13: 144
  CrossrefSuche in Google Scholar
• 4k Houlden CE, Lloyd-Jones GC, Booker-Milburn KI. Org. Lett. 2010; 12: 3090
  CrossrefPubMedSuche in Google Scholar
• 4l Page A, Clayden J. Beilstein J. Org. Chem. 2011; 7: 1327
  CrossrefSuche in Google Scholar
• 4m El-Hiti GA, Hegazy AS, Alotaibi MH, Ajarim MD. ARKIVOC 2012; (vii): 35
  Suche in Google Scholar

Examples for substituted benzenes:
• 5a Clayden J, Turner H, Pickworth M, Adler T. Org. Lett. 2005; 7: 3147
  CrossrefSuche in Google Scholar
• 5b Clayden J, Dufour J. Tetrahedron Lett. 2006; 47: 6945
  CrossrefSuche in Google Scholar
• 5c Burgos PO, Fernández I, Iglesias MJ, García-Granda S, Ortiz FL. Org. Lett. 2008; 10: 537
  CrossrefSuche in Google Scholar
• 5d Castanet A.-S, Tilly D, Véron J.-B, Samanta SS, De A, Ganguly T, Mortier J. Tetrahedron 2008; 64: 3331
  CrossrefSuche in Google Scholar
• 5e Michon C, Murai M, Nakatsu M, Uenishi J, Uemura M. Tetrahedron 2009; 65: 752
  CrossrefSuche in Google Scholar
• 5f Tilly D, Fu J.-M, Zhao B.-P, Alessi M, Catanet A.-S, Snieckus V, Mortier J. Org. Lett. 2010; 12: 68
  CrossrefSuche in Google Scholar
• 5g Slocum DW, Wang S, White CB, Whitley PE. Tetrahedron 2010; 66: 4939
  CrossrefSuche in Google Scholar
• 5h Cho I, Meimetis L, Belding L, Katz MJ, Dudding T, Britton R. Beilstein J. Org. Chem. 2011; 7: 1315
  CrossrefSuche in Google Scholar
• 5i Schmid M, Waldner B, Schnürch M, Mihovilovic MD, Stanetty P. Tetrahedron 2011; 67: 2895
  CrossrefSuche in Google Scholar
• 5j Volz N, Clayden J. Angew. Chem. Int. Ed. 2011; 50: 12148
  CrossrefPubMedSuche in Google Scholar

Examples for substituted heterocycles:
• 6a Robert N, Bonneau A.-L, Hoarau C, Marsais F. Org. Lett. 2006; 8: 6071
  CrossrefSuche in Google Scholar
• 6b Comoy C, Banaszak E, Fort Y. Tetrahedron 2006; 62: 6036
  CrossrefSuche in Google Scholar
• 6c Luisi R, Capriati V, Florio S, Musio B. Org. Lett. 2007; 9: 1263
  CrossrefSuche in Google Scholar
• 6d Clayden J, Hennecke U. Org. Lett. 2008; 10: 3567
  CrossrefSuche in Google Scholar
• 6e McLaughlin M, Marcantonio K, Chen C, Davies IW. J. Org. Chem. 2008; 73: 4309
  CrossrefSuche in Google Scholar
• 6f Capriati V, Florio S, Luisi R, Mazzanti A, Musio B. J. Org. Chem. 2008; 73: 3197
  CrossrefSuche in Google Scholar
• 6g Affortunato F, Florio S, Luisi R, Musio B. J. Org. Chem. 2008; 73: 9214
  CrossrefSuche in Google Scholar
• 6h Musio B, Clarkson GJ, Shipman M, Florio S, Luisi R. Org. Lett. 2009; 11: 325
  CrossrefPubMedSuche in Google Scholar
• 6i Clayton J, Clayden J. Tetrahedron Lett. 2011; 52: 2436
  CrossrefSuche in Google Scholar
• 6j Ibrahim N, Chevot F, Legraverend M. Tetrahedron Lett. 2011; 52: 305
  CrossrefSuche in Google Scholar

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
  CrossrefSuche in Google Scholar
• 7c Smith K, El-Hiti GA, Abdel-Megeed MF, Abdo MA. J. Org. Chem. 1996; 61: 656
  CrossrefSuche in Google Scholar
• 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
  Thieme Connect
• 7g Smith K, El-Hiti GA, Mahgoub SA. Synthesis 2003; 2345
  Thieme Connect
• 7h El-Hiti GA. Synthesis 2003; 2799
  Thieme Connect
• 7i Smith K, El-Hiti GA, Abdel-Megeed MF. Synthesis 2004; 2121
  Thieme Connect
• 7j El-Hiti GA. Synthesis 2004; 363
  Thieme Connect
• 7k Smith K, El-Hiti GA, Hegazy AS. Synthesis 2005; 2951
  Thieme Connect
• 7l Smith K, Barratt ML. J. Org. Chem. 2007; 72: 1031
  CrossrefSuche in Google Scholar
• 8a Smith K, El-Hiti GA, Hegazy AS. Synlett 2009; 2242
  Thieme Connect
• 8b Smith K, El-Hiti GA, Hegazy AS, Fekri A, Kariuki BM. ARKIVOC 2009; (xiv): 266
  Suche in Google Scholar
• 9a Smith K, El-Hiti GA, Hegazy AS. Chem. Commun. 2010; 46: 2790
  CrossrefSuche in Google Scholar
• 9b Smith K, El-Hiti GA, Hegazy AS, Fekri A. Heterocycles 2010; 80: 941
  CrossrefSuche in Google Scholar
• 9c Smith K, El-Hiti GA, Hegazy AS. Synthesis 2010; 1371
  Thieme Connect
• 9d Smith K, El-Hiti GA, Hegazy AS, Kariuki B. Beilstein J. Org. Chem. 2011; 7: 1219
  CrossrefPubMedSuche in Google Scholar
• 10 Simig G, Schlosser M. Tetrahedron Lett. 1988; 29: 4277
  CrossrefSuche in Google Scholar
• 11 Smith K, El-Hiti GA, Alshammari MB. Synthesis 2012; 44: 2013
  Thieme ConnectSuche in Google Scholar
• 12 Simig G, Schlosser M. Tetrahedron Lett. 1991; 32: 1963
  CrossrefSuche in Google Scholar
• 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: ν_max = 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.