Download PDF
Synthesis 2009(4): 627-635  
DOI: 10.1055/s-0028-1083351
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Practical Synthesis of α-Substituted tert-Butyl Acrylates from Meldrum’s Acid and Aldehydes

Christopher G. Frost*a, Stephen D. Penrosea, Robert Gleaveb
a Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK
Fax: +44(1225)386231; e-Mail: c.g.frost@bath.ac.uk;
b Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK
Further Information

Publication History

Received 29 August 2008
Publication Date:
02 February 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

An expeditious synthesis of α-substituted tert-butyl acryl­ates from commercially available aldehydes and Meldrum’s acid has been established. The method benefits from a telescoped condensation-reduction sequence to afford 5-monosubstituted Meldrum’s acid derivatives followed by a Mannich-type reaction triggered by a rapid cycloreversion of the dioxinone ring on heating with tert-butyl alcohol.

Key words

alkenes - Mannich bases - acrylate derivatives - tandem reactions - aldehydes

    References

  • 1a Frechet JMJ. Science  1994,  263:  1710 
    Google Scholar
  • 1b Gordon EM. Barrett RW. Dower WJ. Fodor SPA. Gallop MA. J. Med. Chem.  1994,  37:  1385 
    Google Scholar
  • 1c Sackmann E. Science  1996,  271:  43 
    Google Scholar
  • 1d Langer R. Tirrell DA. Nature  2004,  428:  487 
    Google Scholar
  • 2a Jackson PF. Cole DC. Slusher BS. Stetz SL. Ross LE. Donzanti BA. Trainor DA. J. Med. Chem.  1996,  39:  619 
    Google Scholar
  • 2b Vassiliou S. Mucha A. Cuniasse P. Georgiadis D. Beau F. Kannan R. Murphy G. Knauper V. Rio M.-C. Basset P. Yiotakis A. Dive V. Lucet-Levannier K. J. Med. Chem.  1999,  42:  2610 
    Google Scholar
  • 2c Yajima T. Saito C. Nagano H. Tetrahedron  2005,  61:  10203 
    Google Scholar
  • 2d Chapman CJ. Frost CG. Synthesis  2007,  1 
    Google Scholar
  • 3 Stetter H. Kuhlmann H. Synthesis  1979,  29 
    Article in Thieme ConnectGoogle Scholar
  • For reviews, see:
  • 4a Basavaiah D. Rao JA. Satyanarayana T. Chem. Rev.  2003,  103:  811 
    Google Scholar
  • 4b Ciganek E. In Organic Reactions   Vol. 51:  Paquette LA. Wiley; New York: 1997.  p.201-350  
    Google Scholar
  • 4c Basavaiah D. Rao PD. Hyma RS. Tetrahedron  1996,  52:  8001 
    Google Scholar
  • 4d Drewes SE. Roos GHP. Tetrahedron  1988,  44:  4653 
    Google Scholar
  • 5a Samarat A. Fargeas V. Villieras J. Lebreton J. Amri H. Tetrahedron Lett.  2001,  42:  1273 
    Google Scholar
  • 5b Le Notre J. van Mele D. Frost CG. Adv. Synth. Catal.  2007,  349:  432 
    Google Scholar
  • 6 Negishi E. Tan Z. Liou SY. Liao BQ. Tetrahedron  2000,  56:  10197 
    CrossrefGoogle Scholar
  • 7a Kondolff I. Doucet H. Santelli M. Tetrahedron Lett.  2003,  44:  8487 
    Google Scholar
  • 7b Xi C. Chen C. Lin J. Hong X. Org. Lett.  2005,  7:  347 
    Google Scholar
  • 8a Hin B. Majer P. Tsukamoto T. J. Org. Chem.  2002,  67:  7365 
    Google Scholar
  • 8b Hargrave JD. Bish G. Frost CG. Chem. Commun.  2006,  4389 
    Google Scholar
  • 9a Sato M. Ogasawara H. Sekiguchi K. Kaneko C. Heterocycles  1984,  22:  2563 
    Google Scholar
  • 9b Sato M. Ogasawara H. Kato T. Chem. Pharm. Bull.  1984,  32:  2602 
    Google Scholar
  • 9c Sato M. Yoneda N. Katagiri N. Watanabe H. Kaneko C. Synthesis  1986,  672 
    Google Scholar
  • 9d Sato M. Ban H. Kaneko C. Tetrahedron Lett.  1997,  38:  6689 
    Google Scholar
  • 9e Frost CG. Hartley BC. Org. Lett.  2007,  9:  4259 
    Google Scholar
  • 10 Schuster P. Polansky OE. Wessely F. Monatsh. Chem.  1964,  53 
    Google Scholar
  • 11 Lu J. Li YY. Bai YJ. Tian M. Heterocycles  2004,  63:  583 
    CrossrefGoogle Scholar
  • 12 Rao PS. Venkataratnam RV. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1993,  32:  484 
    Google Scholar
  • 13 Dumas AM. Seed A. Zorzitto AK. Fillion E. Tetrahedron Lett.  2007,  48:  7072 
    CrossrefGoogle Scholar
  • 14a Bigi F. Carloni S. Ferrari L. Maggi R. Mazzacani A. Sartori G. Tetrahedron Lett.  2001,  42:  5203 
    Google Scholar
  • 14b Maggi R. Bigi F. Carloni S. Mazzacani A. Sartori G. Green Chem.  2001,  3:  173 
    Google Scholar
  • 15 Frost CG. Penrose SD. Lambshead K. Raithby PR. Warren JE. Gleave R. Org. Lett.  2007,  9:  2119 
    CrossrefGoogle Scholar
  • 16 Winterfeldt E. J. Prakt. Chem./Chem.-Ztg.  1994,  336:  91 
    Google Scholar
  • 17 Chen BC. Huang X. Ma SM. Synth. Commun.  1987,  1519 
    CrossrefGoogle Scholar
  • 18 Ramachary DB. Kishor M. Ramakumar K. Tetrahedron Lett.  2006,  47:  651 
    CrossrefGoogle Scholar
  • 19 Tóth G. Kövér KE. Synth. Commun.  1995,  3067 
    CrossrefGoogle Scholar
  • 20 Nutaitis CF. Schultz RA. Obaza J. Smith FX. J. Org. Chem.  1980,  45:  4606 
    CrossrefGoogle Scholar