Catalytic Synthesis of Coumarins via Direct Annulations of α,β-Unsaturated Aldehydes and Salicylaldehydes

Abstract

The first organocatalytic approach towards substituted coumarins is reported. Catalytic amounts of in situ generated N-­heterocyclic carbenes (NHC) catalyze a one-pot redox esterification of α,β-unsaturated aldehydes with simultaneous aldol condensation.

Key words

domino reactions - heterocycles - umpolung

References and Notes

• 1a Enders D. Niemeier O. Henseler A. Chem. Rev.  2007,  107:  5606 
• 1b Díez-Gonzáles S. Nolan SP. Marion N. Angew. Chem. Int. Ed.  2007,  46:  2988 
• 1c Nair V. Vellalath S. Babu BP. Chem. Soc. Rev.  2008,  37:  2691 
• 1d Purohit VC. Matla AS. Romo D. Heterocycles  2008,  76:  949 
• 1e Droege T. Glorius F. Angew. Chem. Int. Ed.  2010,  49:  6940 
• 1f De Sarkar S. Studer A. Angew. Chem. Int. Ed.  2010,  49:  9266 
• 1g Thai K. Wang L. Dudding T. Bilodeau F. Gravel M. Org. Lett.  2010,  12:  5708 
• 1h Du G.-F. He L. Gu C.-Z. Dai B. Synlett  2010,  2513 
• 1i Nair V. Vellalath S. Babu BP. Varghese V. Paul RR. Suresh E. Org. Biomol. Chem.  2010,  8:  4861 
• 1j Jiang H. Gschwend B. Albrecht Ł. Jørgensen KA. Org. Lett.  2010,  12:  5052 
• 2 Seebach D. Angew. Chem., Int. Ed. Engl.  1979,  18:  239; Angew. Chem. 1979, 91, 259 
• 3 Enders D. Balensiefer T. Acc. Chem. Res.  2004,  37:  534 
• 4 Stetter H. Angew. Chem., Int. Ed. Engl.  1976,  15:  639 ; Angew. Chem. 1976, 88, 695
• 5a Burstein C. Tschan S. Xie X. Glorius F. Synthesis  2006,  2418 
• 5b Chan A. Scheidt KA. Org. Lett.  2005,  7:  905 
• 5c Zeitler K. Org. Lett.  2006,  8:  637 
• 5d Sohn SS. Rosen EL. Bode JW. J. Am. Chem. Soc.  2004,  126:  14370 
• 5e Burstein C. Glorius F. Angew. Chem. Int. Ed.  2004,  43:  6205 
• 6 He M. Bode JW. Org. Lett.  2005,  7:  3131 
• 7a Toräng J. Vanderheiden S. Nieger M. Bräse S. Eur. J. Org. Chem.  2007,  943 
• 7b Lesch B. Toräng J. Vanderheiden S. Bräse S. Adv. Synth. Catal.  2005,  347:  555 
• 7c Volz N. Bröhmer MC. Bräse S. Synlett  2009,  550 
• 7d Bröhmer MC. Volz N. Bräse S. Synlett  2009,  1383 
• 7e For an account, see: Volz N. Bröhmer MC. Toräng J. Nieger M. Bräse S. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  2009,  48:  1699 
• 8 Borges F. Roleira F. Milhazes N. Santana L. Uriarte E. Curr. Med. Chem.  2005,  12:  887 
• 9 Khanolkar AD. Lu D. Ibrahim M. Duclos RI. Thakur GA. Malan TP. Porreca F. Veerappan V. Tian X. George C. Parrish DA. Papahatjis DP. Makriyannis JA. J. Med. Chem.  2007,  50:  6493 
• 10 Behrenswerth A. Volz N. Toräng J. Hinz S. Bräse S. Müller CE. Bioorg. Med. Chem.  2009,  17:  2842 

11

Typical Procedure
To a round-bottom flask with reflux condenser under argon atmosphere were added salicylaldehyde (20 µL, 23 mg, 0.19 mmol), crotonaldehyde (23 µL, 19 mg, 0.28 mmol, 1.5 equiv), 1,3-diisopropyl-imidazolium chloride (7.0 mg, 37 µmol, 20 mol%), Cs₂CO₃ (60 mg, 0.19 mmol, 1.0 equiv) and o-xylene (1.0 mL). The reaction mixture was heated to 120 ˚C for 12 h. Then H₂O (10 mL) was added, and the resulting mixture was extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with brine (10 ml), dried over MgSO₄, and evaporated under reduced pressure. Purification by chromatography on silica gel, eluting with PE-EtOAc (20:1), yielded the desired product 4ac (26 mg, 81%) as a pale yellow solid.