Solvent-Free, Open-Vessel Microwave-Promoted Heck Couplings: From the mmol to the mol Scale

Abstract

The rapid, microwave-promoted Heck coupling of aryl iodides in open reaction vessels is presented and scale-up of the reactions to the mol scale demonstrated. Reactions are performed using 0.1 mol% palladium acetate as the catalyst, sodium carbonate and tributylamine as bases and tetrabutylammonium bromide as an additive.

Key words

palladium - Heck reaction - catalysis - solvent-free - microwave

References and Notes

• 1 Heck RF. Nolley JP. J. Org. Chem.  1972,  37:  2320 
• 2 Mizoroki T. Mori K. Ozaki A. Bull. Chem. Soc. Jpn.  1971,  44:  581 
• 3 Whitcome NJ. Hii KK. Gibson SE. Tetrahedron  2001,  57:  7449 
• 4 Cabri W. Candiani I. Acc. Chem. Res.  1995,  28:  2 
• 5 de Meijere A. Meyer FE. Angew. Chem., Int. Ed. Engl.  1994,  33:  2379 
• 6 Beletskaya IP. Cheprakov AV. Chem. Rev.  2000,  100:  3009 
• 7 Crisp GT. Chem. Soc. Rev.  1998,  27:  427 
• 8 Dounay AB. Overman LE. Chem. Rev.  2003,  103:  2945 
• 9 Overman LE. Link JT. In Cross Coupling Reactions   Diederich F. Stang PJ. VCH; Weinheim: 1998. 
• For two recent examples, see:
• 10a Overman LE. Watson DA. J. Org. Chem.  2006,  71:  2600 
• 10b Madin A. O’Donnell CJ. Oh T. Old DW. Overman LE. Sharp MJ. J. Am. Chem. Soc.  2005,  127:  18054 
• A number of books on microwave-promoted synthesis have been published recently:
• 11a Kappe CO. Stadler A. Microwaves in Organic and Medicinal Chemistry   Wiley-VCH; Weinheim: 2005. 
• 11b Microwave-Assisted Organic Synthesis, Lidström P., Tierney J. P.   Blackwell; Oxford: 2005. 
• 11c Microwaves in Organic Synthesis   Loupy A. Wiley-VCH; Weinheim: 2002. 
• 11d Hayes BL. Microwave Synthesis: Chemistry at the Speed of Light   CEM Publishing; Matthews NC: 2002. 
• 12 For a recent review, see: Kappe CO. Angew. Chem. Int. Ed.  2004,  43:  6250 
• For other reviews on the general area of microwave-promoted organic synthesis, see:
• 13a Larhed M. Moberg C. Hallberg A. Acc. Chem. Res.  2002,  35:  717 
• 13b Lew A. Krutzik PO. Hart ME. Chamberlain AR. J. Comb. Chem.  2002,  4:  95 
• 13c Lidström P. Tierney JP. Wathey B. Westman J. Tetrahedron  2001,  57:  9225 
• There are numerous reports of microwave-promoted Heck couplings. For reviews covering the topic, see:
• 14a Beletskaya IP. Yus M. Tetrahedron  2005,  61:  11771 
• 14b Larhed M. Moberg C. Hallberg A. Acc. Chem. Res.  2002,  35:  717 
• 15 For the first report, see: Larhed M. Hallberg A. J. Org. Chem.  1996,  61:  9582 
• 16 For an overview, see: Vallin KSA. Emilsson P. Larhed M. Hallberg A. J. Org, Chem.  2002,  67:  6243 
• 17a Arvela RK. Leadbeater NE. J. Org. Chem.  2005,  70:  1786 
• 17b Gil-Molto J. Karlstrom S. Najera C. Tetrahedron  2005,  61:  12168 
• 17c Bergbreiter DE. Furyk S. Green Chem.  2004,  6:  280 
• 17d Botella L. Najera C. J. Org. Chem.  2005,  70:  4360 
• For reviews covering the topic, see:
• 18a Welton T. Smith PJ. Adv. Organomet. Chem.  2004,  51:  251 
• 18b Leadbeater NE. Torenius HM. Tye H. Comb. Chem. High Throughput Screening  2004,  7:  511 
• 19a Xie XG. Lu JP. Chen B. Han JJ. She XG. Pan XF. Tetrahedron Lett.  2004,  45:  809 
• 19b Datta GK. Vallin KSA. Larhed M. Mol. Diversity  2003,  7:  107 
• 19c Vallin KSA. Emilsson P. Larhed M. Hallberg A. J. Org. Chem.  2002,  67:  6243 
• 20a Curran DP. Fischer K. Moura-Letts G. Synlett  2004,  1379 
• 20b Vallin KSA. Zhang QS. Larhed M. Curran DP. Hallberg A. J. Org. Chem.  2003,  68:  6639 
• 21 For a discussion of scale-up of microwave-assisted organic synthesis, see: Roberts BA. Strauss CR. In Microwave-Assisted Organic Synthesis   Lidström P. Tierney JP. Blackwell; Oxford: 2005.  p.210-226 
• 22 For a review, see: Roberts BA. Strauss CR. Acc. Chem. Res.  2005,  38:  653 
• 23 Cablewski T. Faux AF. Strauss CR. J. Org. Chem.  1994,  59:  3408 
• 24a Shieh W.-C. Dell S. Repič O. Tetrahedron Lett.  2002,  43:  5607 
• 24b Khadlikar BM. Madyar VR. Org. Process Res. Dev.  2001,  5:  452 
• 24c Kazba K. Chapados BR. Gestwicki JE. McGrath JL. J. Org. Chem.  2000,  65:  1210 
• 24d Esveld E. Chemat F. van Haveren J. Chem. Eng. Technol.  2000,  23:  279 
• 24e Esveld E. Chemat F. van Haveren J. Chem. Eng. Technol.  2000,  23:  429 
• 25a Marquié J. Salmoria G. Poux M. Laporterie A. Dubac J. Roques N. Ind. Eng. Chem. Res.  2001,  40:  4485 
• 25b Marquié J. Laporte C. Laporterie A. Dubac J. Desmurs J.-R. Ind. Eng. Chem. Res.  2000,  39:  1124 
• 25c Marquié J. Laporterie A. Dubac J. Desmurs J.-R. Roques N. J. Org. Chem.  2001,  66:  421 
• 26 Wilson NS. Sarko CR. Roth GP. Org. Process Res. Dev.  2004,  8:  535 
• 27 Bagley MC. Jenkins RL. Lubinu MC. Mason C. Wood R. J. Org. Chem.  2005,  70:  7009 
• 28a Strauss CR. In Microwaves in Organic Synthesis   Loupy A. Wiley-VCH; Weinheim: 2002.  p.35-60  
• 28b Raner KD. Strauss CR. Trainor RW. Thorn JS. J. Org. Chem.  1995,  60:  2456 
• 29a Lehmann F. Pilotti P. Luthman K. Mol. Diversity  2003,  7:  145 
• 29b Shackelford SA. Anderson MB. Christie LC. Goetzen T. Guzman MC. Hananel MA. Kornreich WD. Li H. Pathak VP. Rabinovich AK. Rajapakse RJ. Truesdale LK. Tsank SM. Vazir HN. J. Org. Chem.  2003,  68:  267 
• 29c Khadilkar BM. Rebeiro GL. Org. Process Res. Dev.  2002,  6:  826 
• 30a Fraga-Dubreuil J. Famelart MH. Bazureau JP. Org. Process Res. Dev.  2002,  6:  374 
• 30b Cleophax J. Liagre M. Loupy A. Petit A. Org. Process Res. Dev.  2000,  4:  498 
• 30c Perio B. Dozias M.-J. Hamelin J. Org. Process Res. Dev.  1998,  2:  428 
• 31 Stadler A. Yousefi BH. Dallinger D. Walla P. Van der Eycken E. Kaval N. Kappe CO. Org. Process Res. Dev.  2003,  7:  707 
• 32 Alcázar J. Diels G. Schoentjes B. QSAR Comb. Sci.  2004,  23:  906 
• 33 Arvela RK. Leadbeater NE. Collins MJ. Tetrahedron  2005,  61:  9349 
• 34 Varma RS. Naicker KP. Liesen PJ. Tetrahedron Lett.  1999,  40:  2075 
• 35 For a survey of their work, see: Koopmans C. Iannelli M. Kerep P. Klink M. Schmitz S. Sinnwell S. Ritter H. Tetrahedron  2006,  62:  4709 
• 36 Jeffery T. Tetrahedron  1996,  52:  10113 
• 37 Kaufmann DE. Nouroozian M. Henze H. Synlett  1996,  1091 
• 38 Jeffery T. David M. Tetrahedron Lett.  1998,  32:  5751 
• 39a Herrmann WA. Böhm VPW. J. Organomet. Chem.  1999,  572:  141 
• 39b Böhm VPW. Herrmann WA. Chem. Eur. J.  2000,  6:  1017 
• 40 Calò V. Nacci A. Lopez L. Mannarini N. Tetrahedron Lett.  2000,  41:  8973 
• 41 Battistuzzi G. Cacchi S. Fabrizi G. Synlett  2002,  439 
• 42 Perosa A. Tundo P. Selva M. Zinovyev S. Testa A. Org. Biomol. Chem.  2004,  2:  2249 
• 44a

  It is important that a suitably sized reaction vessel is used for scale-up reactions in the absence of solvent. It is advised that the contents should occupy no more than 10% of the vessel volume. In addition, microwave power should be carefully modulated. A power no greater than 600 W is advised.

• 44b

  At a first glance it may seem that this would be putting in much more microwave power than in the case of the monomode experiments. However, the relative size of the cavity needs to be considered. Multimode microwaves have large cavities and so power is dissipated over a large area. Monomode equipment has a much smaller cavity and the energy density is up to some 30-40 times higher than the multimode apparatus.

43

It is more appropriate to call the Pd(OAc)₂ a precatalyst since a colloidal palladium species is most likely the catalytically active species.