Organocatalytic Decarboxylative Doebner-Knoevenagel Reactions between Arylaldehydes and Monoethyl Malonate Mediated by a Bifunctional Polymeric Catalyst

Abstract

A bifunctional polystyrene bearing both DMAP and piperidine groups has been prepared and used as an organocatalyst for decarboxylative Doebner-Knoevenagel reactions of arylaldehydes and monoethyl malonate. Isolated yields of the resulting cinnamates were very high, and in all cases only the E-isomer was detected. When a polystyrene catalyst functionalized with only DMAP or piperidine groups was used in these reactions, catalysis was much less efficient. Furthermore, catalysis using a combination of the monofunctional polymers was also less efficient than with the bifunctional polystyrene. Thus, it appears that there is a synergistic effect obtained by co-locating the two different catalytic amine groups on the same polymer backbone.

Key words

Doebner-Knoevenagel reaction - organocatalysis - polystyrene - DMAP - cinnamates

References and Notes

• 1a Knoevenagel E. Ber. Dtsch. Chem. Ges.  1898,  31:  2585 
• 1b Doebner O. Ber. Dtsch. Chem. Ges.  1905,  35:  1136 
• 1c Galat A. J. Am. Chem. Soc.  1945,  68:  376 
• 1d Martin CJ. Schepartz AI. Daubert BF. J. Am. Chem. Soc.  1948,  70:  2601 
• 1e Klein J. Bergmann ED. J. Am. Chem. Soc.  1957,  79:  3452 
• 2a Simpson CJ. Fitzhenry MJ. Stamford NPJ. Tetrahedron Lett.  2005,  46:  6893 
• 2b Sinha AK, Joshi BP, and Sharma A. inventors; US  6,989,467. 
• 2c Sinha AK. Sharma A. Joshi BP. Tetrahedron  2007,  63:  960 
• 2d Bermúdez E. Ventura ON. Méndez PS. J. Phys. Chem. A  2010,  114:  13086 
• 3a Kemme ST. Šmejkal T. Breit B. Adv. Synth. Catal.  2008,  350:  989 
• 3b For a correction, see: Kemme ST. Šmejkal T. Breit B. Adv. Synth. Catal.  2008,  350:  1190 
• 4a List B. Doehring A. Fonseca MTH. Wobser K. van Thienen H. Torres RR. Galilea PL. Adv. Synth. Catal.  2005,  347:  1558 
• 4b List B. Doehring A. Fonseca MTH. Job A. Torres RR. Tetrahedron  2006,  62:  476 ; and references cited therein
• 5a Niwayama S. Cho H. Lin C. Tetrahedron Lett.  2008,  49:  4434 
• 5b Niwayama S. Cho H. Chem. Pharm. Bull.  2009,  57:  508 
• For related reactions coupled to an alcohol oxidation process, see:
• 6a Hall MJ. Pridmore SJ. Williams JMJ. Adv. Synth. Catal.  2008,  350:  1975 
• 6b Pridmore SJ. Williams JMJ. Tetrahedron Lett.  2008,  49:  7413 
• 7 For related reactions using ethyl 4,4,4-trifluroacetoacetate as the pronucleophile, see: Raju BC. Suman P. Chem. Eur. J.  2010,  16:  11840 
• 8 For related decarboxylative aldol and Mannich reactions using monoethyl malonate, see: Baudoux J. Lefebvre P. Legay R. Lasne M.-C. Rouden J. Green Chem.  2010,  12:  252 
• 9 Lu J. Toy PH. Chem. Rev.  2009,  109:  815 
• For reviews of polymer-supported organocatalysts, see:
• 10a Benaglia M. Puglisi A. Cozzi F. Chem. Rev.  2003,  103:  3401 
• 10b Benaglia M. New J. Chem.  2006,  30:  1525 
• 10c Cozzi F. Adv. Synth. Catal.  2006,  348:  1367 
• 10d Gruttadauria M. Giacalone F. Noto R. Chem. Soc. Rev.  2008,  37:  1666 
• 10e Kristensen TE. Hansen T. Eur. J. Org. Chem.  2010,  3179 
• 11a Kan JTW. Toy PH. Tetrahedron Lett.  2004,  45:  6357 
• 11b Zhao L.-J. He HS. Shi M. Toy PH. J. Comb. Chem.  2004,  6:  680 
• 11c But TYS. Tashino Y. Togo H. Toy PH. Org. Biomol. Chem.  2005,  3:  970 
• 11d Zhao L.-J. Kwong CK.-W. Shi M. Toy PH. Tetrahedron  2005,  61:  12026 
• 11e He HS. Zhang C. Ng CK.-W. Toy PH. Tetrahedron  2005,  61:  12053 
• 11f Teng Y. Toy PH. Synlett  2011,  551 
• 12 Kwong CK.-W. Huang R. Zhang M. Shi M. Toy PH. Chem. Eur. J.  2007,  13:  2369 
• 13 Lu J. Toy PH. Synlett  2011,  659 
• 14 Kwong CK.-W. Fu MY. Law HC.-H. Toy PH. Synlett  2010,  2617 
• For perhaps the earliest research regarding the use of a bifunctional polymeric organocatalysts, see:
• 15a Overberger CG. Salamone JC. Yaroslavsky S. J. Am. Chem. Soc.  1967,  89:  6231 
• 15b Overberger CG. Maki H. Macromolecules  1970,  3:  214 
• 15c Overberger CG. Maki H. Macromolecules  1970,  3:  220 
• 15d Overberger CG. Pacansky TJ. Lee J. St. Pierre T. Yaroslavsky S. J. Polym. Sci., Polym. Symp.  1974,  46:  209 
• 15e Overberger CG. Podsiadly CJ. Bioorg. Chem.  1974,  3:  16 
• 15f Overbergcer CG. Podsiadly CJ. Bioorg. Chem.  1974,  3:  35 
• 16 Leung PS.-W. Teng Y. Toy PH. Org. Lett.  2010,  12:  4996 
• 17 Chen J. Yang G. Zhang H. Chen Z. React. Funct. Polym.  2006,  66:  1434 

18

See Supporting Information for details.

19

Increasing the catalyst loading did not significantly affect the isolated yield or stereoselectivity of the reaction.

20

General Procedure for Doebner-Knoevenagel Reactions
Commercially available arylaldehydes 6a-s (0.5 mmol), 7 (0.75 mmol), and catalyst 3 (0.025 mmol) were dissolved in DMF (0.5 mL). The mixture was stirred at 50 ˚C for 15-18 h, and then the reaction mixture was purified directly by column chromatography (EtOAc-hexane) to afford the desired product 8a-s. In all cases only the E-stereoisomer was observed by ^¹H NMR spectroscopy.