A New and Efficient Synthesis of Substituted 2-Hydroxymethyl-2-methyl-2H-chromenes

Abstract

A new and efficient three step procedure for the synthesis of functionalized 2H-chromenes 1 is described, starting from commercially available salicylaldehydes 2 and 2-methylpropenylmagnesium chloride 3, which involves catalytic acid-mediated intramolecular cyclization of phenolic epoxide 5 as the key step.

Key words

2H-chromenes - chromenemethanols - 2,2-disubstituted 2H-chromenes - 2-hydroxymethyl-2-methyl-2H-chromenes - 2H-1-benzopyran

References

• 1a Aizawa Y. Kanaï T. Fujita T. Yoshioka H. Yoshioka T. Heterocycles  1991,  32:  285 
• 1b Holley JH. Hadley KW. Turner CE. J. Pharm. Sci.  1975,  892 
• 1c Mc Hale D. Green J. J. Chem. & Ind.  1962,  1867 
• 1d Benslimane AF. Pouchus YF. Verbist JF. Petit JY. Brion JD. Welin L. J. Clin. Pharmacol.  1995,  35:  298 
• 1e Schweizer EE. Meeder-Nyez D. Chromenes, Chromanones and Chromones, 2H and 4H-1-Benzopyrans   Ellis GP. John Wiley and sons; New York: 1977.  Chap. II. p.81 ; and references cited therein
• 1f Dave E. Kusuni T. Ishitsuka M. Iwaschita T. Kakisawa H. Heterocycles  1984,  22:  2301 
• 1g Nomura T. Fukai T. Hano Y. Tsukamoto K. Heterocycles  1983,  20:  661 
• 1h Ellis GP. In The Chemistry of Heterocyclic Compounds, Chromenes, Chromanes, and Chromones   Weissberger A. Taylor EC. John Wiley; New York: 1977.  Chap. II. p.13 
• 2 Bouzbouz S. Goujon JY. Deplanne J. Kirschleger B. Eur. J. Org. Chem.  2000,  3223 
• 3 Bell D. Davies MR. Green GR. Mann IS. Synthesis  1995,  707 
• 4a Rochfort SJ. Metzger R. Hobbs L. Capon RJ. Aust. J. Chem.  1996,  49:  1217 
• 4b Van Rensburg H. Van Heerden PS. Bezuidenhoudt BCB. Ferreira D. Tetrahedron Lett.  1997,  38:  3089 
• 4c Covington AD. Chem. Soc. Rev.  1997,  111 
• 5a Sukbok C. Grubbs RH. J. Org. Chem.  1998,  63:  864 
• 5b Chauder BA. Kalinin AV. Snieckus V. Synthesis  2001,  140 
• 5c Larock RC. Wei L. Hightowei TR. Synlett  1998,  522 
• 5d Solladié G. Boeffel D. Maignan J. Tetrahedron  1996,  52:  2065 
• 5e Chauder BA. Lopes CC. Lopes RSC. Da Silva AJM. Snieckus V. Synthesis  1998,  279 
• 5f Cruz-Almanza R. Perez-Florès F. Lemini C. Heterocycles  1994,  37:  759 
• 5g Garcias X. Ballester P. Saà JM. Tetrahedron Lett.  1991,  32:  7739 
• 6 David M. Boustie J. Peilloux A. Poupon E. Amoros M. Sauleau A. Pharmaceutical Sciences  1997,  3:  305 
• 7 Kocienski PJ. Protecting Groups   Georg Thieme Verlag; New York NY: 1994.