The Heck arylation of olefins by the substrate-directed Heck-Matsuda strategy using arenediazonium salts, especially the tetrafluoroborates, constitutes an effective way to synthesize functionalized olefins, thus making them more valuable intermediates in organic synthesis. The basic principle of the method relies on the complexation of a cationic δ-aryl-palladium species to a nearby functional group on the substrate in which structural and electronic arrangement governs the arylation process in a regio- and stereoselective manner. The present review highlights this strategy focusing on some selected syntheses accomplished in our laboratory. The synthetic strategy includes the directed arylation of allylic acetates, allylamine derivatives, and functionalized cyclopentene substrates. Illustrative syntheses include the kavalactones yangonine, methysticin, and dehydromethysticin, the antifungal drug naftifine, the phytohormones abamine and abamine SG, the drug cinacalcet, and the muscle relaxant alverine. Moreover, the method was also applied to the successful total synthesis of the sphingosine 1-phosphate agonist VPC01091, a promising drug for the treatment of multiple sclerosis. The examples presented herein demonstrate the substrate-directed strategy method as a general one applicable to metal-catalyzed processes other than the palladium-catalyzed Heck reaction. © 2014 Elsevier Ltd.10 132Hudlicky, T., Reed, J., (2007) The Way of Synthesis, , Wiley-VCH WeinheimTaylor, J.G., Moro, A.V., Correia, C.R.D., (2011) Eur. J. Org. Chem, pp. 1403-1428Kikukawa, K., Matsuda, T., (1977) Chem. Lett., pp. 159-162Roglans, A., Pla-Quintana, A., Moreno-Manas, M., (2006) Chem. Rev., 106, pp. 4622-4643Correia, C.R.D., Oliveira, C.C., Salles, Jr.A.G., Dos Santos, E.A.F., (2012) Tetrahedron Lett., 53, pp. 3325-3328Jiang, Z., Zhang, L., Dong, C., Ma, B., Tang, W., Xu, L., Fan, Q., Xiao, J., (2012) Tetrahedron, 68, pp. 4919-4926Agrawal, J.P., Hodgson, R.D., (2007) Organic Chemistry of Explosives, , Wiley West SussexNorris, T., Bezze, C., Franz, S.Z., Stivanello, M., (2009) Org. Process Res. Dev., 13, pp. 354-357Molinaro, C., Mowat, J., Gosselin, F., O'Shea, P.D., Marcoux, J.-F., Angelaud, R., Davies, I.W.J., (2007) Org. Chem., 72, pp. 1856-1858Oliveira, C.C., Angnes, R.A., Correia, C.R.D.J., (2013) Org. Chem., 78, pp. 4373-4385Moro, A.V., Cardoso, F.S.P., Correia, C.R.D., (2009) Org. Lett., 11, pp. 3642-3645Prediger, P., Barbosa, L.F., Génisson, Y., Correia, C.R.D.J., (2011) Org. Chem., 76, pp. 7737-7749Oliveira, C.C., Dos Santos, E.A.F., Nunes, J.H.B., Correia, C.R.D.J., (2012) Org. Chem., 77, pp. 8182-8190Prediger, P., Da Silva, A.R., Correia, C.R.D., (2014) Tetrahedron, 70, pp. 3333-3341Hoveyda, A.H., Evans, D.A., Fu, G.C., (1993) Chem. Rev., 93, pp. 1307-1370Oliveira, D.F., Severino, E.A., Correia, C.R.D.C., (1999) Tetrahedron Lett., 40, pp. 2083-2086Severino, E.A., Correia, C.R.D.C., (2000) Org. Lett., 2, pp. 3039-3042Severino, E.A., Costenaro, E.R., Garcia, A.L.L., Correia, C.R.D.C., (2003) Org. Lett., 5, pp. 305-308Lumbroso, A., Cooke, M.L., Breit, B., (2013) Angew. Chem. Int. Ed. Engl., 52, pp. 1890-1932Pan, D., Chen, A., Su, Y., Zhou, W., Li, S., Jia, W., Xiao, J., Jiao, N., (2008) Angew. Chem. Int. Ed. Engl., 47, pp. 4729-4732Su, Y., Jiao, N., (2009) Org. Lett., 11, pp. 2980-2983Yao, B., Liu, Y., Wang, M.-K., Li, J.-H., Tang, R.-Y., Zhang, X.-G., Deng, C.-L., (2012) Adv. Synth. Catal., 354, pp. 1069-1076Ripin, D.H., Bourassa, D.E., Brandt, T., Heather, N.F., Castaldi, M.J., Hawkins, J., Johnson, P.J., Wei, L., (2005) Org. Process Res. Dev., 9, pp. 440-450Baxter, C.A., Cleator, E., Alam, M., Davies, A.J., Goodyear, A., O'Hagan, M., (2010) Org. Lett., 12, pp. 668-671Olofsson, K., Sahlin, H., Larhed, M., Hallberg, A.J., (2001) Org. Chem., 66, pp. 544-549Cacchi, S., Fabrizi, G., Goggiamani, A., Sferrazza, A., (2011) Org. Biomol. Chem., 9, pp. 1727-1730Reichardt, C., Welton, T., (2010) Solvents and Solvent Effects in Organic Chemistry, , Wiley-VCH WeinheimOestreich, M., (2009) The Mizoroki-Heck Reaction, , Wiley ChichesterKikukawa, K., Maemura, K., Nagira, K., Wada, F., Matsuda, T., (1980) Chem. Lett, pp. 551-552Kikukawa, K., Nagira, K., Wada, F., Matsuda, T., (1981) Tetrahedron, 37, pp. 31-36Sengupta, S., Bhattacharya, S., (1993) J. Chem. Soc., Perkin Trans. 1, pp. 1943-1944Colas, C., Goeldner, M., (1999) Eur. J. Org. Chem., pp. 1357-1366Pla-Quintana, A., Parella, T., Roglans, A., (2011) Adv. Synth. Catal., 353, pp. 2003-2012Peñafiel, I., Pastor, I.M., Yus, M., (2012) Eur. J. Org. Chem., 2012, pp. 3151-3156Lebel, H., Leogane, O., (2006) Org. Lett., 7, pp. 4107-4110Larue, V., Gharbi-Benarous, J., Acher, F., Valle, G., Crisma, M., Toniolo, C., Azerad, R., Girault, J.-P., (1995) J. Chem. Soc., Perkin Trans. 2, pp. 1111-1126Ung, A.T., Pyne, S.G., Batenburg-Nguyen, U., Davis, A.S., Sherif, A., Biscoff, F., Lesage, A.S.J., (2005) Tetrahedron, 61, pp. 1803-1812Lynch, K.R., Macdonald, T.L., (2006) Sphingosine 1-Phosphate Agonists Comprising Cycloalkanes and 5-Membered Heterocycles Substituted by Amino and Phenyl Groups, , WO Patent 2006088944Zhu, R., Snyder, A.H., Kharel, Y., Schaffter, L., Sun, Q., Kennedy, P.C., Lynch, K.R., Macdonald, T.L.J., (2007) Med. Chem., 50, pp. 6428-6435Fix-Stenzel, S.R., Hayes, M.E., Zhang, X., Wallace, G.A., Grongsaard, P., Schaffter, L.M., Hannick, S.M., Cusack, K.P., (2009) Tetrahedron Lett., 50, pp. 4081-4083Denmark, S.E., Thorarensen, A., Middleton, D.S.J., (1996) Am. Chem. Soc., 118, pp. 8266-8277