Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Substrate-directed Heck-matsuda Arylations: From Curiosity To A Valuable Synthetic Tool

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.10132Hudlicky, 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. 8266-827

Stereoselective Synthesis Of Aryl Cyclopentene Scaffolds By Heck-matsuda Desymmetrization Of 3-cyclopentenol

A new enantioselective Heck-Matsuda desymmetrization reaction was accomplished by using 3-cyclopentenol to produce chiral five-membered 4-aryl cyclopentenol scaffolds in good yields and high ee's, together with some 3-aryl-cyclopentanones as minor products. Mechanistically, the hydroxyl group of 3-cyclopentenol acts as a directing group and is responsible for the cis- arrangement in the formation of the 4-aryl-cyclopentenols.20411311713121Sun, C., Potter, B., Morken, J.P., (2014) J. Am. Chem. Soc., 136, pp. 6534-6537Chen, X., Xiong, F., Chen, W., He, Q., Chen, F., (2014) J. Org. Chem., 79, pp. 2723-2728Tay, D.W., Leung, G.Y.C., Yeung, Y.-Y., (2014) Angew. Chem., 126, pp. 5261-5264(2014) Angew. Chem. Int. Ed., 53, pp. 5161-5164Rong, Z.-Q., Pan, H.-J., Yan, H.-L., Zhao, Y., (2014) Org. Lett., 16, pp. 208-211Roux, C., Candy, M., Pons, J.-M., Chuzel, O., Bressy, C., (2014) Angew. Chem., 126, pp. 785-789(2014) Angew. Chem. Int. Ed., 53, pp. 766-770García-Urdiales, E., Alfonso, I., Gotor, V., (2011) Chem. Rev., 111, pp. 110-180Yang, W., Yan, J., Long, Y., Zhang, S., Liu, J., Zeng, Y., Cai, Q., (2013) Org. Lett., 15, pp. 6022-6025Chu, L., Wang, X.-C., Moore, C.E., Rheingold, A.L., Yu, J.-Q., (2013) J. Am. Chem. Soc., 135, pp. 16344-16347Shibasaki, M., Ohshima, T., (2009) The Mizoroki-Heck Reaction, pp. 463-483. , (Ed.: M. Oestreich), John Wiley & Sons, ChichesterRoglans, A., Pla-Quintana, A., Moreno-Mañas, M., (2006) Chem. Rev., 106, pp. 4622-4643Taylor, J.G., Moro, A.V., Correia, C.R.D., (2011) Eur. J. Org. Chem., 2011, pp. 1403-1428Felpin, F.-X., Nassar-Hardy, L., Lecallonnec, F., Fouquet, E., (2011) Tetrahedron, 67, pp. 2815-2831Oestreich, M., (2014) Angew. Chem., 126, pp. 2314-2317(2014) Angew. Chem. Int. Ed., 53, pp. 2282-2285Prediger, P., Silva, A.R.D., Correia, C.R.D., (2014) Tetrahedron, 70, pp. 3333-3341Oger, N., Lecallonnec, F., Jacquemin, D., Fouquet, E., Legrognec, E., Felpin, F.X., (2014) Adv. Synth. Catal., 356, pp. 1065-1071Schmidt, B., Berger, R., (2013) Adv. Synth. Catal., 355, pp. 463-476Elbakouri, O., Fernández, M., Brun, S., Pla-Quintana, A., Roglans, A., (2013) Tetrahedron, 69, pp. 9761-9765Kawagishi, F., Toma, T., Inui, T., Yokoshima, S., Fukuyama, T., (2013) J. Am. Chem. Soc., 135, pp. 13684-13687Schmidt, B., Elizarov, N., Berger, R., Hölter, F., (2013) Org. Biomol. Chem., 11, pp. 3674-3691Correia, C.R.D., Oliveira, C.C., Salles, A.G., Jr., Santos, E.A.F., (2012) Tetrahedron Lett., 53, pp. 3325-3328Oliveira, C.C., Angnes, R.A., Correia, C.R.D., (2013) J. Org. Chem., 78, pp. 4373-4385Werner, E.W., Mei, T.-S., Burckle, A.J., Sigman, M.S., (2012) Science, 338, pp. 1455-1458Heasley, B., (2014) Curr. Org. Chem., 18, pp. 641-686Kobayashi, Y., Nakata, K., Ainai, T., (2005) Org. Lett., 7, pp. 183-186Liu, S., Zhou, J., (2013) Chem. Commun., 49, pp. 11758-11760Xu, L., Hilton, M.J., Zhang, X., Norrby, P.-O., Wu, Y.-D., Sigman, M.S., Wiest, O., (2014) J. Am. Chem. Soc., 136, pp. 1960-1967Dang, Y., Qu, S., Wang, Z.-X., Wang, X., (2014) J. Am. Chem. Soc., 136, pp. 986-998Oliveira, C.C., Dossantos, E.A.F., Nunes, J.H.B., Correia, C.R.D., (2012) J. Org. Chem., 77, pp. 8182-8190Huang, L., Qi, J., Wu, X., Huang, K., Jiang, H., (2013) Org. Lett., 15, pp. 2330-2333Smadja, W., Czernecki, S., Ville, G., Georgoulis, C., (1987) Organometallics, 6, pp. 166-169Eshthiaghhosseini, H., Beyramabadi, S., Morsali, A., Housaindokht, M.R., (2010) J. Mol. Struct., 941, pp. 138-143Keith, J.A., Oxgaard, J., Goddard, W.A., III, (2006) J. Am. Chem. Soc., 128, pp. 3132-3133Berhal, F., Wu, Z., Genet, J.-P., Ayad, T., Ratovelomanana-Vidal, V., (2011) J. Org. Chem., 76, pp. 6320-6326Csizmadiová, J., Mečiarová, M., Rakovský, E., Horváth, B., Šebesta, R., (2011) Eur. J. Org. Chem., pp. 6110-6116Gendrineau, T., Chuzel, O., Eijsberg, H., Genet, J.-P., Darses, S., (2008) Angew. Chem., 120, pp. 7783-7786(2008) Angew. Chem. Int. Ed., 47, pp. 7669-767

Intermolecular Enantioselective Heck-matsuda Arylations Of Acyclic Olefins: Application To The Synthesis Of β-aryl-γ-lactones And β-aryl Aldehydes

We describe herein a synthetically useful method for the enantioselective intermolecular Heck-Matsuda arylation of acyclic allylic alcohols. Aryldiazonium tetrafluoroborates were applied as arylating agents in the presence of Pd(TFA)2 and a chiral, commercially available, bisoxazoline ligand. The methodology is straightforward, robust, scalable up to a few grams, and of broad scope allowing the synthesis of a range of β-aryl-carbonyl compounds in good to high enantioselectivities and yields. This new enantioselective Heck-Matsuda arylation allowed the synthesis of β-aryl-γ-lactones and β-aryl aldehydes, which play a vital role as key intermediates in the synthesis of the biologically active compounds, such as (R)-baclofen, (R)-rolipram, (S)-curcumene, (S)-dehydrocurcumene, and (S)-tumerone. © 2013 American Chemical Society.78943734385Ozawa, F., Kubo, A., Hayashi, T., (1991) J. Am. Chem. Soc., 113, pp. 1417-1419Cartney, D.M., Guiry, P.J., (2011) Chem. Soc. Rev., 40, pp. 5122-5150Coeffard, V., Guiry, P.J., (2010) Curr. Org. Chem., 14, pp. 212-229Dounay, A.B., Overman, L.E., (2003) Chem. Rev., 103, pp. 2945-2964Yang, Z., Zhou, J., (2012) J. Am. Chem. Soc., 134, pp. 11833-11835Zhao, L., Li, Z., Chang, L., Xu, J., Yao, H., Wu, X., (2012) Org. Lett., 14, pp. 2066-2069Gao, P., Cook, S.P., (2012) Org. Lett., 14, pp. 3340-3343Gøgsig, T.M., Kleimark, J., Nilsson Lill, S.O., Korsager, S., Lindhardt, A.T., Norrby, P.-O., Skrydstrup, T., (2012) J. Am. Chem. Soc., 134, pp. 443-452Shard, A., Sharma, N., Bharti, R., Dadhwal, S., Kumar, R., Sinha, A.K., (2012) Angew. Chem., Int. Ed., 51, pp. 12250-12253Gottumukkala, A.L., De Vries, J.G., Minnaard, A.J., (2011) Chem. - Eur. J., 17, pp. 3091-3095Oestreich, M., (2009) The Mizoroki-Heck Reaction, , Ed. Wiley: Chichester, UKKoga, Y., Sodeoka, M., Shibasaki, M., (1994) Tetrahedron Lett., 35, pp. 1227-1230Yonehara, K., Mori, K., Hashizume, T., Chung, K.-G., Ohe, K., Uemura, S., (2000) J. Organomet. Chem., 603, pp. 40-49Werner, E.W., Mei, T.-S., Burckle, A.J., Sigman, M.S., (2012) Science, 338, pp. 1455-1458. , When this manuscript was in preparation, Sigman et al. reported the Heck-Matsuda arylation of acyclic alkenyl alcohols using a strategy similar to oursCorreia, C.R.D., Oliveira, C.C., Salles Jr., A.G., Dos Santos, E.A.F., (2012) Tetrahedron Lett., 53, pp. 3325-3328Roglans, A., Pla-Quintana, A., Moreno-Manas, M., (2006) Chem. Rev., 106, pp. 4622-4643Taylor, J.G., Moro, A.V., Correia, C.R.D., (2011) Eur. J. Org. Chem., pp. 1403-1428Felpin, F.-X., Nassar-Hardy, L., Le Callonnec, F., Fouquet, E., (2011) Tetrahedron, 67, pp. 2815-2831Barancelli, D.A., Salles, A.G., Taylor, J.G., Correia, C.R.D., (2012) Org. Lett., 14, pp. 6036-6039Oliveira, C.C., Dos Santos, E.A.F., Nunes, J.H.B., Correia, C.R.D., (2012) J. Org. Chem., 77, pp. 8182-8190Soldi, C., Moro, A.V., Pizzolatti, M.G., Correia, C.R.D., (2012) Eur. J. Org. Chem., pp. 3607-3616Moro, A.V., Rodrigues Dos Santos, M., Correia, C.R.D., (2011) Eur. J. Org. Chem., pp. 7259-7270Werner, E.W., Sigman, M.S., (2011) J. Am. Chem. Soc., 133, pp. 9692-9695Schmidt, B., Hölter, F., Kelling, A., Schilde, U., (2011) J. Org. Chem., 76, pp. 3357-3365Cacchi, S., Fabrizi, G., Goggiamani, A., Sferrazza, A., (2011) Org. Biomol. Chem., 9, pp. 1727-1730Prediger, P., Barbosa, L.F., Génisson, Y., Correia, C.R.D., (2011) J. Org. Chem., 76, pp. 7737-7749Callonnec, F.L., Fouquet, E., Felpin, F.-X., (2011) Org. Lett., 13, pp. 2646-2649Susperregui, N., Miqueu, K., Sotiropoulos, J.-M., Le Callonnec, F., Fouquet, E., Felpin, F.-X., (2012) Chem. - Eur. J., 18, pp. 7210-7218Felpin, F.-X., Miqueu, K., Sotiropoulos, J.-M., Fouquet, E., Ibarguren, O., Laudien, J., (2010) Chem. - Eur. J., 16, pp. 5191-5204Sabino, A.A., MacHado, A.H.L., Correia, C.R.D., Eberlin, M.N., (2004) Angew. Chem., Int. Ed., 43, pp. 2514-2518(2004) Angew. Chem., Int. Ed., 43, p. 4389Vogt, M., Ceylan, S., Kirschning, A., (2010) Tetrahedron, 66, pp. 6450-6456. , Dibenzilidene-acetone (dba) impurities are sometimes difficult to remove, requiring a reduction step before purification of the reaction products. For an example, seeTundo, P., Selva, M., (2002) Acc. Chem. Res., 35, pp. 706-716Arcadi, A., Bernocchi, E., Cacchi, S., Marinelli, F., (1991) Tetrahedron, 47, pp. 1525-1540Cacchi, S., Fabrizi, G., Goggiamani, A., Sferrazza, A., (2009) Synlett, pp. 973-977Zhou, L., Liu, X., Ji, J., Zhang, Y., Hu, X., Lin, L., Feng, X., (2012) J. Am. Chem. Soc., 134, pp. 17023-17026Petersen, K.S., Stoltz, B.M., (2011) Tetrahedron, 67, pp. 4352-4357Xu, S., Wang, Z., Zhang, X., Zhang, X., Ding, K., (2008) Angew. Chem., Int. Ed., 47, pp. 2840-2843Brenna, E., Caraccia, N., Fuganti, C., Fuganti, D., Grasselli, P., (1997) Tetrahedron: Asymmetry, 8, pp. 3801-3805Braun, M., Unger, C., Opdenbusch, K., (1998) Eur. J. Org. Chem., pp. 2389-2396Honda, T., Ishikawa, F., Kanai, K., Sato, S., Kato, D., Tominaga, H., (1996) Heterocycles, 42, pp. 109-112Csizmadiová, J., Mečiarová, M., Rakovský, E., Horváth, B., Šebesta, R., (2011) Eur. J. Org. Chem., pp. 6110-6116Berhal, F., Wu, Z., Genet, J.-P., Ayad, T., Ratovelomanana-Vidal, V., (2011) J. Org. Chem., 76, pp. 6320-6326Gendrineau, T., Chuzel, O., Eijsberg, H., Genet, J.-P., Darses, S., (2008) Angew. Chem., Int. Ed., 47, pp. 7669-7672Chung, Y.-C., Janmanchi, D., Wu, H.-L., (2012) Org. Lett., 14, pp. 2766-2769Čorić, I., Müller, S., List, B., (2010) J. Am. Chem. Soc., 132, pp. 17370-17373Felice, V.D., De Renzi, A., Fraldi, N., Panunzi, B., (2009) Inorg. Chim. Acta, 362, pp. 2015-2019Calò, V., Nacci, A., Monopoli, A., Ferola, V., (2007) J. Org. Chem., 72, pp. 2596-2601Afewerki, S., Breistein, P., Pirttilä, K., Deiana, L., Dziedzic, P., Ibrahem, I., Córdova, A., (2011) Chem. - Eur. J., 17, pp. 8784-8788Bräse, S., Höfener, S., (2005) Angew. Chem., Int. Ed., 44, pp. 7879-7881Stivala, C.E., Zakarian, A., (2011) J. Am. Chem. Soc., 133, pp. 11936-11939Xu, H.-J., Zhu, F.-F., Shen, Y.-Y., Wan, X., Feng, Y.-S., (2012) Tetrahedron, 68, pp. 4145-4151Malkov, A.V., Friscourt, F., Bell, M., Swarbrick, M.E., Kočovský, P., (2008) J. Org. Chem., 73, pp. 3996-4003Kotsuki, H., Shinohara, T., Fujioka, S., (2001) Heterocycles, 55, pp. 237-242Kim, S.-G., (2008) Tetrahedron Lett., 49, pp. 6148-6151Akagawa, K., Akabane, H., Sakamoto, S., Kudo, K., (2008) Org. Lett., 10, pp. 2035-203

The First Examples Of The Enantioselective Heck-matsuda Reaction: Arylation Of Unactivated Cyclic Olefins Using Chiral Bisoxazolines

Successful enantioselective Heck-Matsuda arylations were accomplished for the first time using chiral bisoxazolines as ligands. Enantioselective Heck arylations were performed with several cyclic nonactivated olefins to provide the Heck products in 63-96% isolated yields and in enantiomeric excesses of 54% up to 84%. © 2012 Elsevier Ltd. All rights reserved.532633253328Tietze, L.F., Ila, H., Bell, H.P., (2004) Chem. Rev., 104, p. 3453Melchiorre, P., Marigo, M., Carlone, A., Bartoli, G., (2008) Angew. Chem., Int. Ed., 47, p. 4137Walsh, P.J., Kozlowski, M., (2009) Fundamentals of Asymmetric Catalysis, , University Science Books Sausalito pp. 549-576Roglans, A., Pla-Quintana, A., Moreno-Manas, M., (2006) Chem. Rev., 106, p. 4622. , For reviews, seeTaylor, J.G., Moro, A.V., Correia, C.R.D., (2011) Eur. J. Org. Chem., p. 1403Felpin, F.-X., Nassar-Hardy, L., Callonnec, F.L., Fouquet, E., (2011) Tetrahedron, 67, p. 2815Nassar-Hardy, L., Fabre, S., Amer, A.M., Fouquet, E., Felpin, F.-X., (2012) Tetrahedron Lett., 53, p. 338Schwalm, C.S., De Castro, I.B.D., Ferrari, J., De Oliveira, F.L., Aparicio, R., Correia, C.R.D., (2012) Tetrahedron Lett., 53, p. 1660Taylor, J.G., Correia, C.R.D., (2011) J. Org. Chem., 76, p. 857Da Penha, E.T., Forni, J.A., Biajoli, A.F.P., Correia, C.R.D., (2011) Tetrahedron Lett., 52, p. 6342Taylor, J.G., Ribeiro, R.S., Correia, C.R.D., (2011) Tetrahedron Lett., 52, p. 3861De Azambuja, F., Correia, C.R.D., (2011) Tetrahedron Lett., 52, p. 42Siqueira, F.A., Taylor, J.G., Correia, C.R.D., (2010) Tetrahedron Lett., 51, p. 2102Garcia, A.L.L., Carpes, M.J.S., Montes De Oca, A.C.B., Santos, M.A.G., Santana, C.C., Correia, C.R.D., (2005) J. Org. Chem., 70, p. 1050Garcia, A.L.L., Correia, C.R.D., (2003) Tetrahedron Lett., 44, p. 1553Severino, E.A., Costenaro, E.R., Garcia, A.L.L., Correia, C.R.D., (2003) Org. Lett., 5, p. 305Kikukawa, K., Matsuda, T., (1977) Chem. Lett., p. 159Johnson, J.S., Evans, D.A., (2000) Acc. Chem. Res., 33, p. 325Evans, D.A., Scheidt, K.A., Johnston, J.N., Willis, M.C., (2001) J. Am. Chem. Soc., 123, p. 4480Evans, D.A., Johnston, J.N., (1999) Org. Lett., 1, p. 865Evans, D.A., Johnson, D.S., (1999) Org. Lett., 1, p. 5985Nishiyama, H., Sakaguchi, H., Nakamura, T., Horihata, M., Kondo, M., Itoh, K., (1989) Organometallics, 8, p. 846. , For PyBox ligand seeTietze, L.F., Sommer, K.M., Zinngrebe, J., Stecker, F., (2005) Angew. Chem., 117, p. 262. , For an excellent example of a conventional Heck reaction employing chiral bisoxazoline as ligand, see:, Angew. Chem. Int. Ed. 2005, 44, 257Pastre, J.C., Correia, C.R.D., (2009) Adv. Synth. Catal., 351, p. 1217Pastre, J.C., Genisson, Y., Saffon, N., Dandurand, J., Correia, C.R.D., (2010) J. Braz. Chem. Soc., 21, p. 821. , For previous attempts of an enantioselective HM reaction using chiral ionic liquids, seeAshimori, A., Overman, L.E., (1992) J. Org. Chem., 57, p. 4571Amatore, C., Jutand, A., Suarez, A., (1993) J. Am. Chem. Soc., 115, p. 9531Cabri, W., Candiani, I., Bedeschi, A., Santi, R., (1993) J. Org. Chem., 58, p. 7421Sato, Y., Sodeoka, M., Shibasaki, M., (1990) Chem. Lett., 1953Sato, Y., Watanabe, S., Shibasaki, M., (1992) Tetrahedron Lett., 33, p. 2589Sato, Y., Nukui, S., Sodeoka, M., Shibasaki, M., (1994) Tetrahedron, 50, p. 371Shibasaki, M., Sodeoka, M., (1994) J. Synth. Org. Chem. Jpn., 52, p. 955Grunewald, G.L., Ye, Q., (1988) J. Org. Chem., 53, p. 4021. , For application of similar carbocycles in the synthesis of bioactive molecules seeMoriaty, R.M., Enache, L.A., Zhao, L., Gilardi, R., Mattson, M.V., Prakash, O., (1998) J. Med. Chem., 41, p. 468Hancock, R.D., (1992) J. Chem. Edu., 69, p. 615. , For an interesting reviewMoro, A.V., Cardoso, F.S.P., Correia, C.R.D., (2009) Org. Lett., 11, p. 3642Prediger, P., Barbosa, L.F., Genisson, Y., Correia, C.R.D., (2011) J. Org. Chem., 76, p. 773

Stereoselective Arylation Of Substituted Cyclopentenes By Substrate-directable Heck-matsuda Reactions: A Concise Total Synthesis Of The Sphingosine 1-phosphate Receptor (s1p1) Agonist Vpc01091

We describe herein an efficient and diastereoselective substrate-directable Heck-Matsuda reaction with nonactivated five-membered olefins. The carbamate acts as the main directing group in the arylation process allowing the synthesis of several functionalized aryl cyclopentenes in good to excellent diastereoselectivities (>85:15) and in isolated yields ranging from 41 to 90%. No double bond isomerizations were observed in these Heck reactions, and the newly created benzylic centers were preserved in all cases examined. The substrate directable Heck arylation approach was successfully applied in a straightforward total synthesis of the sphingosine 1-phosphate receptor-subtype 1 (S1P1) agonist VPC01091 by a concise and practical route involving 5 steps in 40% overall yield. © 2012 American Chemical Society.771881828190Beletskaya, I.P., Cheprakov, A.V., (2000) Chem. Rev., 100, p. 3009Alonso, F., Beletskaya, I.P., Yus, M., (2005) Tetrahedron, 61, p. 11771Negishi, E.-I., (2002) Handbook of Organopalladium Chemistry for Organic Synthesis, , Wiley-Interscience: New YorkTsuji, J., (2004) Palladium Reagents and Catalyst, , Wiley: Chichester, U.KOestreich, M., (2009) The Mizoroki-Heck Reaction, , Wiley: Chichester, U.KRoglans, A., Pla-Quintana, A., Moreno-Manas, M., (2006) Chem. Rev., 106, p. 4622Taylor, J.G., Moro, A.V., Correia, C.R.D., (2011) Eur. J. Org. Chem., p. 1403Felpin, F.-X., Nassar-Hardy, L., Callonnec, F.L., Fouquet, E., (2011) Tetrahedron, 67, p. 2815Moro, A.V., Cardoso, F.S.P., Correia, C.R.D., (2009) Org. Lett., 11, p. 3642Prediger, P., Barbosa, L.F., Génisson, Y., Correia, C.R.D., (2011) J. Org. Chem., 76, p. 7737Hoveyda, A.H., Evans, D.A., Fu, G.C., (1993) Chem. Rev., 93, p. 1307Hodgson, D.M., Thompson, A.J., Wadman, S., Keats, C.J., (1999) Tetrahedron, (55), p. 10815Stewart, C., Keitz, B.K., Kuhn, K.M., Thomas, R.M., Grubbs, R.H., (2010) J. Am. Chem. Soc., 132, p. 8534Niwayama, S., Cho, H., Lin, C., (2008) Tetrahedron Lett., 49, p. 4434Lebel, H., Leogane, O., (2006) Org. Lett., 7, p. 4107Soldi, C., Moro, A.V., Pizzolatti, M.G., Correia, C.R.D., (2012) Eur. J. Org. Chem., p. 3607Nassar-Hardy, L., Fabre, S., Amer, A.M., Fouquet, E., Felpin, F.-X., (2012) Tetrahedron Lett., 53, p. 338Schwalm, C.S., De Castro, I.B.D., Ferrari, J., De Oliveira, F.L., Aparício, R., Correia, C.R.D., (2012) Tetrahedron Lett., 53, p. 1660Werner, E.W., Sigman, M.S., (2011) J. Am. Chem. Soc., 133, p. 9692Taylor, J.G., Correia, C.R.D., (2011) J. Org. Chem., 76, p. 857Da Penha, E.T., Forni, J.A., Biajoli, A.F.P., Correia, C.R.D., (2011) Tetrahedron Lett., 52, p. 6342Schmidt, B., Holter, F., Kelling, A., Schilde, U., (2011) J. Org. Chem., 76, p. 3357Taylor, J.G., Ribeiro, R.S., Correia, C.R.D., (2011) Tetrahedron Lett., 52, p. 3861De Azambuja, F., Correia, C.R.D., (2011) Tetrahedron Lett., 52, p. 42Siqueira, F.A., Taylor, J.G., Correia, C.R.D., (2010) Tetrahedron Lett., 51, p. 2102Correia, C.R.D., Oliveira, C.C., Salles Jr., A.G., Dos Santos, E.A.F., (2012) Tetrahedron Lett., 53, p. 3325Kikukawa, K., Matsuda, T., (1977) Chem. Lett., p. 159Kikukawa, K., Maemura, K., Nagira, K., Wada, F., Matsuda, T., (1980) Chem. Lett., p. 551Kikukawa, K., Nagira, K., Wada, F., Matsuda, T., (1981) Tetrahedron, 37, p. 31Sengupta, S., Bhattacharya, S., (1993) J. Chem. Soc. Perkin Trans. 1, 17, p. 1943Colas, C., Goeldner, M., (1999) Eur. J. Org. Chem., p. 1357Salabert, J., Sebstián, R.M., Vallribera, A., Roglans, A., Nájera, C., (2011) Tetrahedron., 45, p. 8659Pla-Quintana, A., Parella, T., Roglans, A., (2011) Adv. Synth. Catal., 353, p. 2003Artuso, E., Barbero, M., Degani, I., Dughera, S., Fochi, R., (1981) Tetrahedron, 37, p. 31Nelson, M.L., Ismail, M.Y., McIntyre, L., Bhatia, B., Viski, P., Hawkins, P., Rennie, G., Levy, S.B., (2003) J. Org. Chem., 68, p. 5838Peñafiel, I., Pastor, I.M., Yus, M., (2012) Eur. J. Org. Chem., p. 3151Larue, V., Gharbi-Benarous, J., Acher, F., Valle, G., Crisma, M., Toniolo, C., Azerad, R., Girault, J.-P., (1995) J. Chem. Soc., Perkin Trans., 2, p. 1111Ung, A.T., Pyne, S.G., Batenburg-Nguyen, U., Davis, A.S., Sherif, A., Biscoff, F., Lesage, A.S.J., (2005) Tetrahedron, 61, p. 1803Lynch, 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., (2007) J. Med. Chem., 50, p. 6428Fix-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, p. 4081Wallace, G.A., Gordon, T.D., Hayes, M.E., Konopacki, D.B., Fix-Stenzel, S.R., Zhang, X., Grongsaard, P., Stoffel, R.H., (2009) J. Org. Chem., 74, p. 4886Strader, C.R., Pearce, C.J., Oberlies, N.H., (2011) J. Nat. Prod., 74, p. 900Nakano, T., Miyahara, M., Itoh, T., Kamimura, A., Eur. J. Org. Chem., 2012, p. 2161Lewis, N., McKillop, A., Taylor, R.J.K., Watson, R.J., (1995) Synth. Commun., 25, p. 561Moro, A.V., Santos, M.R., Correia, C.R.D., (2011) Eur. J. Org. Chem., p. 7259Singh, R., Just, G., (1989) J. Org. Chem., 54, p. 4453Denmark, S.E., Thorarensen, A., Middleton, D.S., (1996) J. Am. Chem. Soc., 118, p. 8266Still, W.C., Kahn, M., Mitra, A., (1978) J. Org. Chem., 43, p. 2923Plé, K., Haudrechy, A., Probst, N.P., (2010) Tetrahedron, 66, p. 5030Dunker, M.F.W., Starkey, E.B., Jenkins, G.L., (1936) J. Am. Chem. Soc., 58, p. 2308Starkey, E.B., (1943) Org. Synth., 2, p. 22