β,β-Disubstituted R,β-unsaturated esters may serve as valuable derivatives for the preparation of other highly functionalized systems found in many natural products and marketed drugs. The stereoselective synthesis of unsymmetrical β,β-diarylacrylate compounds possessing two similar aromatic groups remains a substantial challenge. A simple and convenient stereoselective protocol for the preparation of β,β- disubstituted acrylates via a Heck-Matsuda reaction is reported. Good to high yields were accomplished by a "ligand-free" Pd-catalyzed arylation reaction of cinnamate esters with arenediazonium tetrafluoroborates. Both electron-deficient and electron-rich arenediazonium salts could be employed as arylating reagents, and cinnamate esters were generally more reactive when substituted with an electron-donating group. The overall methodology is highly stereoselective, and this attribute was taken advantage of in the asymmetric Cu-catalyzed 1,4 reduction reaction to provide β,β-diarylpropanoates in high enantioselectivities. The synthesis of a 3-aryl indole and a chiral 4-aryl-2-quinolone from β,β-diarylacrylates was achieved by cyclization in the presence of a diphosphine ligated CuH catalyst. A convenient route for the asymmetric formal synthesis of the psychoactive compound (-)-Indatraline is also presented. © 2010 American Chemical Society.763857869Kikukawa, K., Matsuda, T., (1977) Chem. Lett., 159. , For a review, see:Roglans, A., Pla-Quintana, A., (2006) Moreno-Manas Chem. Rev., 106, p. 4622Ollis, (1968) Chem. Commun., 1392Alarcon, A.B., Cuesta- Rubio, O., Perez, J.C., Piccinelli, A.L., Rastrelli, L., (2008) J. Nat. Prod., 71, p. 1283Pastre, J.C., Correia, C.R.D., (2009) Adv. Synth. Catal., 351, p. 1217Gallagher, B.D., Taft, R., Lipshutz, B.H., (2009) Org. Lett., 11 (23), p. 5374Malamas, M.S., Palka, C.L., (1996) J. Heterocycl. Chem., 33 (2), p. 475. , For examples see:Almansa, C.A., (1996) J. Med. Chem., 39, p. 2197Yu, K.-L., (1996) J. Med. Chem., 39 (12), p. 2411Yamamoto, Y., Kirai, N., Harada, Y., (2008) Chem. Commun., p. 2010Cacchi, S., (1984) Palmieri Synthesis, 7, p. 575. , For reports on Heck coupling reactions of aryl halides to R,ß- unsaturated carbonyl compounds, see:Baek, G.H., (1999) Bull. Korean Chem. Soc., 20 (2), p. 232Bernini, R., Cacchi, S., Salve, I.D., Fabrizi, G., (2006) Synlett, 18, p. 2947Moreno-Manas, M., Perez, M., Pleixats, R., (1996) Tetrahedron Lett., 37, p. 7449Gurtler, C., Buchwald, S.L., (1999) Chem.;Eur. J., 5, p. 3107Botella, L., Carmen Nájera, C., (2005) J. Org. Chem., 70 (11), p. 4360Calo, V., Nacci, A., Monopoli, A., Laera, S., Cioffi, N., (2003) J. Org. Chem., 68, p. 2929Ikemoto, T., (2004) Tetrahedron Lett., 45, p. 7757Song, F., (2007) J. Med. Chem., 50, p. 2807Sengupta, S., Bhattacharyya, S., (2001) Tetrahedron Lett., 42, p. 2035Kikukawa, K., Nagira, K., Wada, F., Matsuda, T., (1981) Tetrahedron, 37, p. 31Kikukawa, K., Matsuda, T., (1977) Chem. Lett., 159Deutsch, C., Krause, N., Lipshutz, B.H., (2008) Chem. Rev., 108, p. 2916. , For selected reviews, see:Hii, K.K., (2006) Pure Appl. Chem., 78, p. 341Enders, D., Wang, C., Liebich, J.X., (2009) Chem.;Eur. J., 15, p. 11058Enders, D., Saint-Dizier, A., Lannou, M-I., Lenzen, A., (2006) Eur. J. Org. Chem., 29Ballini, R., Bosica, G., Fiorini, D., Palmieri, A., Petrini, M., (2005) Chem. Rev., 105, p. 933Enders, D., Lttgen, K., Narine, A.A., (2007) Synthesis, 7, p. 959Jerphagnon, T., Pizzuti, M.G., Minnaard, A.J., Feringa, B.L., (2009) Chem. Soc. Rev., 38, pp. 1039-1075Harutyunyan, S.R., Den Hartog, T., Geurts, K., Minnard, A.J., Feringa, B.L., (2008) Chem. Rev., 108, p. 2824Tsogoeva, S.B., (2007) Eur. J. Org. Chem., 1701Chrisyoffers, J., Koripelly, G., Rosiak, A., Rssle, M., (2007) Synthesis, 1279Yoo, K., Kim, H., Yun, J., (2009) Chem.;Eur. J, 15 (42), p. 11134Brestensky, D.M., Huseland, D.E., McGettigan, C., Stryker, J.M., (1988) Tetrahedron Lett., 29, p. 3749Mahoney, W.S., Brestensky, D.M., Stryker, J.M., (1988) J. Am. Chem. Soc., 110, p. 291Brestensky, D.M., Stryker, J.M., (1989) Tetrahedron Lett., 30, p. 5677Koenig, T.M., Daeuble, J.F., Brestensky, D.M., Stryker, J.M., (1990) Tetrahedron Lett., 31, p. 3237Appella, D.H.L., Moritani, Y., Shintani, R., Ferreira, E.M., Buchwald, S.L., (1999) J. Am. Chem. Soc., 121, p. 9473Lipshutz, B.H., Servesko, J.M., Taft, B.R., (2004) J. Am. Chem. Soc., 126 (27), p. 8352Dhanak, D., Kaura, A.C., Shaw, A., (2001) Chem. Abstr., 135, p. 357951. , For some recent references, see: WO 2001085172, 2001Norman, P., (2002) Curr. Opin. Invest. Drugs, 3, p. 313Venet, M., End, D., Angibaud, P., (2003) Curr. Top. Med. Chem., 3, p. 1095Van Cutsem, E., Van De Velde, H., Karasek, P., Oettle, H., Vervenne, W.L., Szawlowski, A., Schoffski, P., Von Hoff, D.J., (2004) Clin. Oncol., (22), p. 1430Freeman, G.A., Andrews III, C.W., Hopkins, A.L., Lowell, G.S., Schaller, L.T., Cowan, J.R., Gonzales, S.S., Chan, J.H., (2004) J. Med. Chem., (47), p. 5923Li, Q., Woods, K.W., Wang, W., Lin, N.-H., Claiborne, A., Gu, W.-Z., Cohen, J., Sham, H.L., (2005) Bioorg.Med. Chem.Lett., 15, p. 2033Kim, Y., Shin, E., Beak, P., Park, Y.S., (2006) Synthesis, 22, p. 3805Paquin, J.-F., Steptenson, C.R.J., Defieber, C., Carreira, E.M., (2005) Org. Lett., 7 (3821)Hong, D., Chen, Z., Lin, X., Wang, Y., (2010) Org. Lett., 12, p. 4608Indatraline (Lu 19-005is a potent psychoactive compound with high binding and inhibitory activity for neuronal monoamine reuptake sites, including dopamine and serotonin transporters and is currently being investigated as medication to treat cocaine addiction. For further information, see:Bogeso, K.P., Christensen, A.V., Hyttel, J., Liljefors, T., (1985) J. Med. Chem., 28, p. 1817Hyttel, J., Larsen, J., (1985) J. Neurochem., 44, p. 1615Arnt, J., Christensen, A.V., Hyttel, J., (1985) Naunyn-Schmiedeberg's Arch. Pharmacol., 329, p. 101Hurd, Y.L., Ungerstedt, U., (1989) Eur. J. Pharmacol., 166, p. 251Negus, S.S., Brandt, M.R., Mello, N.K., (1999) J. Pharmacol. Exp. Ther., 291, pp. 60-69Davies, H.M.L., Gregg, T.M., (2002) Tetrahedron Lett., 43, p. 4951Froimowitz, M., Wu, K.M., Moussa, A., Haidar, R.M., Jurayj, J., George, C., Gardner, E.L., (2000) J. Med. Chem., 43, p. 4981