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Synthesis 2012(5): 686-693  
DOI: 10.1055/s-0031-1289650
PSP
© Georg Thieme Verlag Stuttgart ˙ New York

Highly Efficient and Enantioselective α-Arylation of Cycloalkanones by Scandium-Catalyzed Diazoalkane-Carbonyl Homologation

Victor L. Rendina, Hilan Z. Kaplan, Jason S. Kingsbury*
Eugene F. Merkert Chemistry Center, Boston College, 2609 Beacon St., Chestnut Hill, MA 02467, USA
Fax: +1(617)5522705; e-Mail: jason.kingsbury@bc.edu;
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Publication History

Received 31 October 2011
Publication Date:
20 December 2011 (online)

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Abstract

Functionalized α-tertiary and -quaternary 2-arylcycloalkanones are rapidly accessed by scandium(III) triflate-catalyzed diazo­alkane-carbonyl homologations. Recent developments have allowed for carbon insertion reactions to be performed with catalyst loadings as low as 0.5 mol% on scales up to 5 mmol. Pairing readily available bis- and tris(oxazoline) based ligands with scandium triflate allows access to arylated medium ring carbocycles with enantioselectivities up to 98:2 er and >98% yield. The formal C-C insertion of aryldiazo­methanes into unsubstituted cycloalkanones provides a single-step solution to the ongoing challenge of α-arylation.

Key words

diazo compounds - scandium - asymmetric catalysis - ring expansion - arylation

    References

  • 1a Dolling UF. Davis P. Grabowski EJJ. J. Am. Chem. Soc.  1984,  106:  446 
    Search in Google Scholar
  • 1b Corey EJ. Xu F. Noe MC. J. Am. Chem. Soc.  1997,  119:  12414 
    Search in Google Scholar
  • 1c Behenna DC. Stoltz BM. J. Am. Chem. Soc.  2004,  126:  15044 
    Search in Google Scholar
  • 1d Doyle AG. Jacobsen EN. J. Am. Chem. Soc.  2005,  127:  62 
    Search in Google Scholar
  • 1e Trost BM. Xu J. J. Am. Chem. Soc.  2005,  127:  2846 
    Search in Google Scholar
  • 1f Braun M. Meier T. Synlett  2005,  2968 
  • 1g Graening T. Hartwig JF. J. Am. Chem. Soc.  2005,  127:  17192 
    Search in Google Scholar
  • 1h Imai M. Hagihara A. Kawasaki H. Manabe K. Koga K. J. Am. Chem. Soc.  1994,  116:  8829 
    Search in Google Scholar
  • For unrelated catalytic entries to such products, see:
  • 1i Luchaco-Cullis C. Hoveyda AH. J. Am. Chem. Soc.  2002,  124:  8192 
    Search in Google Scholar
  • 1j Shen Y.-M. Wang B. Shi Y. Tetrahedron Lett.  2006,  47:  5455 
    Search in Google Scholar
  • For a lead reference on the α-derivatization of aldehydes by organocatalysis, see:
  • 1k Mastracchio A. Warkentin AA. Walji AM. MacMillan DWC. Proc. Natl. Acad. Sci. U.S.A.  2010,  107:  20648 
    Search in Google Scholar
  • 2a Meyers AI. Williams DR. Druelinger M. J. Am. Chem. Soc.  1976,  98:  3032 
    Search in Google Scholar
  • 2b Job A. Janeck CF. Bettray W. Peters R. Enders D. Tetrahedron  2002,  58:  2253 
    Search in Google Scholar
  • 3a Alexander M. Altman RA. Buchwald SL. J. Am. Chem. Soc.  2009,  131:  9900 
    Search in Google Scholar
  • 3b Chieffi A. Kamikawa K. Åhman J. Fox JM. Buchwald SL. Org. Lett.  2001,  3:  1897 
    Search in Google Scholar
  • 4a Åhman J. Wolfe JP. Troutman MV. Palucki M. Buchwald SL. J. Am. Chem. Soc.  1998,  120:  1918 
    Search in Google Scholar
  • 4b Hamada T. Chieffi A. Åhman J. Buchwald SL.
    J. Am. Chem. Soc.  2002,  124:  1261 
    Search in Google Scholar
  • 4c Chae J. Yun J. Buchwald SL. Org. Lett.  2004,  6:  4809 
    Search in Google Scholar
  • 4d Liao X. Weng Z. Hartwig JF. J. Am. Chem. Soc.  2008,  130:  195 
    Search in Google Scholar
  • 5a Ishihara K. Nakamura S. Kaneeda M. Yamamoto H. J. Am. Chem. Soc.  1996,  118:  12854 
    Search in Google Scholar
  • 5b Yanagisawa A. Inanami H. Yamamoto H. Chem. Commun.  1998,  1573 
  • 5c Nakamura S. Kaneeda M. Ishihara K. Yamamoto H. J. Am. Chem. Soc.  2002,  122:  8120 
    Search in Google Scholar
  • 5d Ishihara K. Nakashima D. Hiraiwa Y. Yamamoto H. J. Am. Chem. Soc.  2003,  125:  24 
    Search in Google Scholar
  • 5e Cheon CH. Yamamoto H. J. Am. Chem. Soc.  2008,  130:  9246 
    Search in Google Scholar
  • 5f Yanagisawa A. Touge T. Arai T. Angew. Chem. Int. Ed.  2005,  44:  1546 
    Search in Google Scholar
  • 6a Moebius DC. Kingsbury JS. J. Am. Chem. Soc.  2009,  131:  878 
    Search in Google Scholar
  • 6b Wommack AJ. Moebius DC. Travis AL. Kingsbury JS. Org. Lett.  2009,  11:  3202 
    Search in Google Scholar
  • 6c Rendina VL. Moebius DC. Kingsbury JS. Org. Lett.  2011,  13:  2004 
    Search in Google Scholar
  • 7a Gutsche CD. Org. React.  1954,  8:  364 
    Search in Google Scholar
  • 7b Gutsche CD. Redmore D. In Carbocyclic Ring Expansion Reactions   Hart H. Karabatsos GJ. Academic Press; New York: 1968.  p.81-98  
  • 8a Javed MI. Brewer M. Org. Lett.  2007,  9:  1789 
    Search in Google Scholar
  • 8b Furrow ME. Myers AG. J. Am. Chem. Soc.  2004,  126:  12222 
    Search in Google Scholar
  • 8c Holton TL. Shechter H. J. Org. Chem.  1995,  60:  4725 
    Search in Google Scholar
  • 11a Tang Y. Zhou J. J. Am. Chem. Soc.  2002,  124:  9030 
    Search in Google Scholar
  • 11b Zhou J. Tang Y. Chem. Soc. Rev.  2005,  34:  664 
    Search in Google Scholar
  • 12 Davies IW. Gerena L. Castonguay L. Senanayake CH. Larsen RD. Verhoevena TR. Reidera PJ. Chem. Commun.  1996,  1753 
  • 13 Armarego WLF. Chai CLL. Purification of Laboratory Chemicals   5th ed.:  Butterworth-Heinemann; Oxford: 2003. 
    Search in Google Scholar
  • 14Tertiary 2-arylcyclopentanones are known to racemize on silica gel. See:
  • 14 Shen Y.-M. Wang B. Shi Y. Angew. Chem. Int. Ed.  2006,  45:  1429 
    Search in Google Scholar
9

Rendina V. L.; Kingsbury, J. S. Submitted to J. Org. Chem. for publication.

10

Though not studied in the context of cycloalkanone ring expansions, heteroaromatic substrates are well tolerated in the Sc-catalyzed homologation of aldehydes. See reference 6b.