Synthesis of N-Alkoxyindol-2-ones by Copper-Catalyzed Intramolecular N-Arylation of Hydroxamates

Abstract

The first example of copper-catalyzed intramolecular N-arylation of hydroxamic acid derivatives is presented. Based on this transformation a new method for the synthesis of N-alkoxyindol-2-ones from 2-(2-bromoaryl)acetylhydroxamates has been developed. The reaction conditions tolerate standard hydroxyl protecting groups on the hydroxylamine moiety and are also applicable for the synthesis of six-membered N-alkoxybenzolactams.

Key words

copper - arylation - cyclization - lactams - hydoxamic ­acids

References and Notes

• 1 Henmi T. Sakamoto T. Kikugawa Y. Heterocycles  1997,  44:  157 
• 2 Kikugawa Y. Shimada M. Matsumoto K. Heterocycles  1994,  37:  293 
• 3 Pedras MSC. Chumala PB. Suchy M. Phytochemistry  2003,  64:  949 
• 4 Kitajima M. Nakamura T. Kogure N. Ogawa M. Mitsuno Y. Ono K. Yano S. Aimi N. Takayama H.
  J. Nat. Prod.  2006,  69:  715 
• 5a Kato H. Yoshida T. Tokue T. Nojiri Y. Hirota H. Ohta T. Williams RM. Tsukamoto S. Angew. Chem. Int. Ed.  2007,  46:  2254 
• 5b Tsukamoto S. Kato H. Samizo M. Nojiri Y. Onuki H. Hirota H. Ohta T. J. Nat. Prod.  2008,  71:  2064 
• 6a Bouerat L. Fensholdt J. Liang X. Havez S. Nielsen SF. Hansen JR. Bolvig S. Andersson C. J. Med. Chem.  2005,  48:  5412 
• 6b Bouerat LME, Fensholdt J, Nielsen SF, Liang X, Havez SE, Andersson EC, Jensen L, and Hansen JR. inventors; WO  2005058309.  ; Chem. Abstr. 2005, 143, 97259
• 7 Parkes KEB. Ermert P. Fässler J. Ives J. Martin JA. Merrett JH. Obrecht D. Williams G. Klumpp K.
  J. Med. Chem.  2003,  46:  1153 
• 8 El-Faham A. Albericio F. Eur. J. Org. Chem.  2009,  1499 
• 9a Di Carlo FJ. J. Am. Chem. Soc.  1944,  66:  1420 
• 9b Wright WB. Collins KH. J. Am. Chem. Soc.  1956,  78:  221 
• 9c Somei M. Sato H. Kaneko C. Heterocycles  1983,  20:  1797 
• 9d Kende AS. Thurston J. Synth. Commun.  1990,  20:  2133 
• 10 Neset SM. Benneche T. Undheim K. Acta Chem. Scand.  1993,  47:  1141 
• 11a Kikugawa Y. Kawase M. J. Am. Chem. Soc.  1984,  106:  5728 
• 11b Kawase M. Kitamura T. Kikugawa Y. J. Org. Chem.  1989,  54:  3394 
• 11c Kikugawa Y. Shimada M. Chem. Lett.  1987,  1771 
• 11d For a review, see: Kikugawa Y. Heterocycles  2009,  78:  571 
• For reviews on copper-catalyzed cross-couplings, see:
• 12a Ley SV. Thomas AW. Angew. Chem. Int. Ed.  2003,  42:  5400 
• 12b Beletskaya IP. Cheprakov AV. Coord. Chem. Rev.  2004,  248:  2337 
• 12c Evano G. Blanchard N. Toumi M. Chem. Rev.  2008,  108:  3054 
• For selected reviews on palladium-catalyzed cross-couplings, see:
• 12d Schlummer B. Scholz U. Adv. Synth. Catal.  2004,  346:  1599 
• 12e Surry DS. Buchwald SL. Angew. Chem. Int. Ed.  2008,  47:  6338 
• 12f Surry DS. Buchwald SL. Chem. Sci.  2011,  2:  27 
• 13 Wasa M. Yu J.-Q. J. Am. Chem. Soc.  2008,  130:  14058 
• 14 Jones KL. Porzelle A. Hall A. Woodrow MD. Tomkinson NCO. Org. Lett.  2008,  10:  797 
• 15 Porzelle A. Woodrow MD. Tomkinson NCO. Org. Lett.  2009,  11:  233 
• 16 Xing X. Wu J. Luo J. Dai W.-M. Synlett  2006,  2099 
• 17 van den Hoogenband A. den Hartog JAJ. Lange JHM. Terpstra JW. Tetrahedron Lett.  2004,  45:  8535 
• 18 Yang BH. Buchwald SL. Org. Lett.  1999,  1:  35 
• 19 Klapars A. Huang X. Buchwald SL. J. Am. Chem. Soc.  2002,  124:  7421 
• For reports of the benefit of molecular sieves in the copper-catalyzed cross-coupling reaction, see:
• 20a Cristau H.-J. Cellier PP. Spindler J.-F. Taillefer M. Chem. Eur. J.  2004,  10:  5607 
• 20b Shen Y. Li M. Wang S. Zhan T. Tan Z. Guo C.-C. Chem. Commun.  2009,  953 
• 20c Yao B. Zhang Y. Li Y. J. Org. Chem.  2010,  75:  4554 
• 21a Ma D. Cai Q. Zhang H. Org. Lett.  2003,  5:  2453 
• 21b Zhang H. Cai Q. Ma D. J. Org. Chem.  2005,  70:  5164 
• 22 Hosseinzadeh R. Tajbakhsh M. Mohadjerani M. Mehdinejad H. Synlett  2004,  1517 
• 23a Altman RA. Buchwald SL. Org.Lett.  2007,  9:  643 
• 23b de Lange B. Lambers-Verstappen MH. Schmieder-van de Vondervoot L. Sereinig N. de Rijk R. de Vries AHM. de Vries JG. Synlett  2006,  3105 
• 24 Shafir A. Buchwald SL. J. Am. Chem. Soc.  2006,  128:  8742 
• For recent examples where the hydoxamate N-O moiety serves as an internal oxidant, see:
• 29a Guimond N. Gouliaras C. Fagnou K. J. Am. Chem. Soc.  2010,  132:  6908 
• 29b Patureau FW. Glorius F. Angew. Chem. Int. Ed.  2011,  50:  1977 
• 30 For a review on oxidative homocoupling reactions, see: Klussmann M. Sureshkumar D. Synthesis  2011,  353 

25

General Procedure
To an oven-dried vial equipped with a stirrer bar, hydroxamate (1.0 equiv, 0.2 mmol), copper(II) bromide (10 mol%), K₂CO₃ (2.0 equiv, 0.4 mmol) and 3 Å MS (100 wt%) were added. The vial was closed using an aluminium open-top seal with PTFE-faced septum, flushed with argon before addition of dry toluene (2 mL) and DMEDA (20 mol%) and stirred at the appropriate temperature for the appropriate time (Table  [¹] ). After cooling the reaction mixture was diluted with EtOAc (5 mL) then filtered through a short silica plug and washed with EtOAc. The solvent was removed in vacuo, and the crude product was purified by flash column chromatography on silica gel eluting with EtOAc-hexane (1:5) to give the product.

26

Compound 2a was obtained in 61% yield from iodo hydroxamate 1b if K₃PO₄ was used as base. For a report of the advantage of K₃PO₄ as compared to K₂CO₃ in copper-catalyzed amidation of aryliodides, see ref. 19.

27

Product 2a from chloro hydroxamate 1c was obtained in 43% yield if reaction was carried out for 1 h in MeCN at sample concentration 0.2 mmol/mL.

28

Crystallographic data for 3 have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-827122, and may be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CD2 1EZ, UK; fax: [phone]; or [e-mail].