Synthesis 2012; 44(12): 1798-1805
DOI: 10.1055/s-0031-1290775
special topic
© Georg Thieme Verlag Stuttgart · New York

Synthesis of N-Alkyl-Substituted 4-Quinolones via Tandem Alkenyl and Aryl C–N Bond Formation

Jun Shao
a  Department of Chemistry, Shanghai University, Shanghai 200444, P. R. of China, Fax: +86(21)66132065   Email: xubin@shu.edu.cn
,
Xiaomei Huang
a  Department of Chemistry, Shanghai University, Shanghai 200444, P. R. of China, Fax: +86(21)66132065   Email: xubin@shu.edu.cn
,
Xiaohu Hong
a  Department of Chemistry, Shanghai University, Shanghai 200444, P. R. of China, Fax: +86(21)66132065   Email: xubin@shu.edu.cn
,
Bingxin Liu
a  Department of Chemistry, Shanghai University, Shanghai 200444, P. R. of China, Fax: +86(21)66132065   Email: xubin@shu.edu.cn
,
Bin Xu*
a  Department of Chemistry, Shanghai University, Shanghai 200444, P. R. of China, Fax: +86(21)66132065   Email: xubin@shu.edu.cn
b  State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. of China
c  Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, East China Normal University, Shanghai 200062, P. R. of China
› Author Affiliations
Further Information

Publication History

Received: 04 January 2012

Accepted: 01 March 2012

Publication Date:
03 April 2012 (eFirst)

Abstract

N-Alkyl-substituted 4-quinolones are present as the key structural motif in many marketed drugs. An efficient one-step tandem amination approach was developed to afford N-alkyl-substituted 4-quinolones in high yields from easily accessible o-chloroaryl acetylenic ketones and functionalized alkyl amines. The approach complements and extends our previous work. Compared with other reported methods, the current method provides a very simple and convenient route.

Supporting Information

 
  • References

    • 1a Michael JP. Nat. Prod. Rep. 1997; 14: 605
    • 1b Fort DM, Litvak J, Chen JL, Lu Q, Phuan P.-W, Cooper R, Bierer DE. J. Nat. Prod. 1998; 61: 1528
    • 1c Oliphant CM, Green GM. Am. Fam. Physician. 2002; 65: 455
    • 1d Mitscher LA. Chem. Rev. 2005; 105: 559
    • For selected examples, see:

    • 2a Li L, Wang H.-K, Kuo S.-C, Wu T.-S, Lednicer D, Lin CM, Hamel E, Lee K.-H. J. Med. Chem. 1994; 37: 1126
    • 2b Xia Y, Yang Z.-Y, Xia P, Hackl T, Hamel E, Mauger A, Wu J.-H, Lee K.-H. J. Med. Chem. 2001; 44: 3932
    • 2c Hadjeri M, Peiller E.-L, Beney C, Deka N, Lawson MA, Dumontet C, Boumendjel A. J. Med. Chem. 2004; 47: 4964
    • For selected examples, see:

    • 3a Llinàs-Brunet M, Bailey MD, Ghiro E, Gorys V, Halmos T, Poirier M, Rancourt J, Goudreau N. J. Med. Chem. 2004; 47: 6584
    • 3b Lucero Bd A, Gomes CR. B, Frugulhetti IC. d. P. P, Faro LV, Alvarenga L, de Souza MC. B. V, de Souza TM. L, Ferreira VF. Bioorg. Med. Chem. Lett. 2006; 16: 1010
    • 3c Frutos RP, Haddad N, Houpis IN, Johnson M, Smith-Keenan LL, Fuchs V, Yee NK, Farina V, Faucher A.-M, Brochu C, Haché B, Duceppe J.-S, Beaulieu P. Synthesis 2006; 2563
    • For selected examples, see:

    • 4a Nakamura S, Kozuka M, Bastow KF, Tokuda H, Nishino H, Suzuki M, Tatsuzaki J, Morris NatschkeS. L, Kuo S.-C, Lee K.-H. Bioorg. Med. Chem. Lett. 2005; 13: 4396
    • 4b Dubar F, Anquetin G, Pradines B, Dive D, Khalife J, Biot C. J. Med. Chem. 2009; 52: 7954
    • 4c Dubar F, Wintjens R, Martins-Duarte ES, Vommaro RC, de Souza W, Dive D, Pierrot C, Pradines B, Wohlkonig A, Khalife J, Biot C. Med. Chem. Commun. 2011; 2: 430
  • 6 Ding D, Li X, Wang X, Du Y, Shen J. Tetrahedron Lett. 2006; 47: 6997
  • 7 Huang J, Chen Y, King AO, Dilmeghani M, Larsen RD, Faul MM. Org. Lett. 2008; 10: 2609
  • 8 Jones CP, Anderson KW, Buchwald SL. J. Org. Chem. 2007; 72: 7968
    • For selected examples, see:

    • 9a Haddad N, Tan J, Farina V. J. Org. Chem. 2006; 71: 5031
    • 9b Genelot M, Dufaud V, Djakovitch L. Tetrahedron 2011; 67: 976
    • 10a Coppola GM. J. Heterocycl. Chem. 1982; 19: 727
    • 10b Yoshino Y, Kurahashi T, Matsubara S. J. Am. Chem. Soc. 2009; 131: 7494
    • 11a Zhao T, Xu B. Org. Lett. 2010; 12: 212
    • 11b Sun C, Xu B. J. Org. Chem. 2008; 73: 7361
    • 11c Wang C, Sun C, Weng F, Gao M, Liu B, Xu B. Tetrahedron Lett. 2011; 52: 2984
    • 11d Ye W, Mo J, Zhao T, Xu B. Chem. Commun. 2009; 3246
  • 12 Kanzian T, Nigst TA, Maier A, Pichl S, Mayr H. Eur. J. Org. Chem. 2009; 6379
  • 13 Hu A, You T, Tan Y, Wang Y. Chin. J. Synth. Chem. 2006; 14: 640
  • 14 Reddy PG, Baskaran S. Tetrahedron Lett. 2001; 42: 6775
  • 15 Audisio D, Messaoudi S, Peyrat J.-FO, Brion J.-D, Alami M. J. Org. Chem. 2011; 76: 4995
  • 16 Carr RM, Sutherland DR. J. Labelled Compd. Radiopharm. 1994; 34: 961
    • For selected examples, see:

    • 17a Almeida AI. S, Silva AM. S, Cavaleiro JA. S. Synlett 2010; 462
    • 17b Cross RM, Monastyrskyi A, Mutka TS, Burrows JN, Kyle DE, Manetsch R. J. Med. Chem. 2010; 53: 7076
  • 18 Venkataraman S, Barange DK, Pal M. Tetrahedron Lett. 2006; 47: 7317
    • 19a Hessian KO, Flynn BL. Org. Lett. 2005; 8: 243
    • 19b Cross RM, Manetsch R. J. Org. Chem. 2010; 75: 8654
  • 20 Bernini R, Cacchi S, Fabrizi G, Sferrazza A. Synthesis 2009; 1209
  • 21 For the stereochemistry of intermediate 4, see: Fuchs F, Eller G, Holzer W. Molecules 2009; 14: 3814
  • 22 For the timescale needed for addition of n-butylamine to substrate 1a, see the Supporting Information
  • 23 Elbe H, Tiemann R, Dutzmann S, Stenzel K, Yuan LP, Cao Y, Deng CZ. PCT Int. Appl WO9845283, 1997
  • 24 Keivanloo A, Bakherad M, Bahramian B, Rahmani M, Taheri SA. N. Synthesis 2011; 325
  • 25 Karpov AS, Müller TJ. J. Org. Lett. 2003; 5: 3451
  • 26 Shim SC, Chae SA, Lee DY, Lim HS, Kalinin VN. J. Korean Chem. Soc. 1994; 38: 774