An element through the looking glass: Exploring the Au-C, Au-H and Au-O energy landscape

Gold, the archetypal “noble metal”, used to be considered of little interest in catalysis. It is now clear that this was a misconception, and a multitude of gold-catalysed transformations has been reported. However, one consequence of the long-held view of gold as inert metal is that its organometallic chemistry contains many “unknowns”, and catalytic cycles devised to explain gold's reactivity draw largely on analogies with other transition metals. How realistic are such mechanistic assumptions? In the last few years a number of key compound classes have been discovered that can provide some answers. This Perspective attempts to summarise these developments, with particular emphasis on recently discovered gold(III) complexes with bonds to hydrogen, oxygen, alkenes and CO ligands

A Morita-baylis-hillman Adduct Allows The Diastereoselective Synthesis Of Styryl Lactones

We disclosed herein a diastereoselective approach for the total syntheses of (±)-Leiocarpin A and (±)-Goniodiol. These biologically active styryl lactones were obtained from a common intermediate, prepared in five steps and 40% overall yield, using a simple synthetic sequence starting from a Morita-Baylis-Hillman adduct. The total syntheses of these styryl lactones were accomplished in nine steps. This is the first report on the total synthesis of this class of natural products starting from Morita-Baylis-Hillman adduct. © 2011 Elsevier Ltd. All rights reserved.524661806184Blázquez, M.A., Bermejo, A., Zafra-Polo, M.C., Cortes, D., (1999) Phytochem. Anal., 10, p. 161Fang, X.P., Anderson, J.E., Chang, C.J., Fanwick, P.E., McLaughlin, J.L., (1990) J. Chem. Soc. Perkin Trans, 1, p. 1665Mereyala, H.B., Joe, M., (2001) Curr. Med. Chem. Anticancer Agents, 1, p. 293De Fatima, A., Modolo, L.V., Conegero, L.S., Pili, R.A., Ferreira, C.V., Kohn, L.K., De Carvalho, J.E., (2006) Curr. Med. Chem., 13, p. 3371De Fátima, A., Marquissolo, C., De Albuquerque, S., Carraro- Abrahão, A.A., Pilli, R.A., (2006) Eur. J. Med. Chem., 10, p. 1210Ridzuan, M.A.R.M., Ruenruetai, U., Rain, A.N., Khozirah, S., Zakiah, I., (2006) Trop. Biomed., 23, p. 140Talapatra, S.K., Basu, D., De, T., Goswani, S., Talapatra, B., (1985) Indian J. Chem. Sect. B, 24 B, p. 29Lan, Y.H., Chang, F.R., Liaw, C.C., Wu, C.C., Chiang, M.Y., Wu, Y.C., (2005) Planta Med., 71, p. 153Sam, T., Sew-Yeu, C., Matsjeh, S., Gan, E.K., Razak, D., Mohamed, A.L., (1987) Tetrahedron Lett., 71, p. 153Gao, S.-G., Wu, X.-H., Sim, K.-Y., Tan, B.K.H., Pereira, J.T., Goh, S.-H., (1988) Tetrahedron, 54, p. 2143Jewers, K., Davis, J.B., Dougan, J., MacHanda, A.H., Blunden, G., Kyi, A., Wetchapinan, S., (1972) Phytochemistry, 11, p. 2025Mondon, M., Gesson, J.-P., (2006) Curr. Org. Synth., 3, p. 41. , For some reviews concerning the synthesis of styryl lactones seeZhao, G., Wu, B., Wu, X., Zhang, Ya.Z., (2005) Mini-Rev. Org. Chem., 2, p. 333Prasad, K.R., Dhaware, M.G., (2007) Synlett, p. 1112. , For some reviews concerning the synthesis of styryl lactones seeSabitha, G., Sudhakar, K., Yadav, J.S., (2007) Synthesis, p. 385Prasad, K.R., Gholap, S.L., (2007) Tetrahedron Lett., 48, p. 4679Mu, Q., Tang, W., Li, C., Lu, Y., Sun, H., Zheng, H., Hao, X., Xu, B., (1999) Heterocycles, 51, p. 2969Mu, Q., Li, C.M., He, Y.N., Sun, H.D., Zheng, H.L., Lu, Y., Zheng, Q.T., Jiang, W., (1999) Chin. Chem. Lett., 10, p. 35Chen, J., Lin, G.Q., Liu, H.Q., (2004) Tetrahedron Lett., 45, p. 8111. , At the present only two approaches for the total synthesis of Leiocarpin A have been describedNagaiah, K., Sreenu, D., Purnima, K.V., Rao, R.S., Yadav, J.S., (2009) Synthesis, p. 1386Fang, X.-P., Anderson, J.E., Chang, C.-J., McLaughlin, J.L., (1991) J. Nat. Prod., 54, p. 1034Tsubuki, M., Kanai, T., Honda, T., (1992) J. Chem. Soc. Chem. Commun., p. 1640Surivet, J.-P., Vatele, J.-M., (1999) Tetrahedron, 55, p. 13011. , For some ouststanding examples concerning the total synthesis of Goniodiol, seeTsukubi, M., Kanai, K., Nagase, H., Honda, T., (1999) Tetrahedron, 55, p. 2493Ramachandran, P.V., Chandra, J.S., Reddy, M.V.R., (2002) J. Org. Chem., 67, p. 7547Tate, E.W., Dixon, D.J., Ley, S.V., (2006) Org. Biomol. Chem., 4, p. 1698Yoshida, T., Yamauchi, S., Tago, R., Maruyama, M., Akyiama, K., Sugahara, T., Kishida, T., Koba, Y., (2008) Biosci. Biotechnol. Biochem., 72, p. 2342Yadav, J.S., Premalatha, K., Harshavardhan, S.J., Reddy, B.V.S., (2008) Tetrahedron Lett., 49, p. 6765Yadav, J.S., Das, S., Mishra, A.K., (2010) Tetrahedron: Asymmetry, 21, p. 2443Kiran, I.N.C., Reddy, R.S., Suryavanshi, G., Sudalai, A., (2011) Tetrahedron Lett., 52, p. 438Shi, M., Wang, F.-J., Zhao, M.-X., Wei, Y., (2011) The Chemistry of the Morita-Baylis-Hillman Reaction, , RSC Publishing Cambrigde, UKBasavaiah, D., Reddy, B.S., Badsara, S.S., (2010) Chem. Rev., 110, p. 5447De Souza, R.O.M.A., Miranda, L.S.M., (2010) Mini-Rev. Org. Chem., 7, p. 212Singh, V., Batra, S., (2008) Tetrahedron, 64, p. 4511Basavaiah, D., Rao, K.V., Reddy, R.J., (2007) Chem. Soc. Rev., 36, p. 1581Almeida, W.P., Coelho, F., (2001) Quim. Nova, 23, p. 98Amarante, G.W., Cavallaro, M., Coelho, F., (2010) Tetrahedron Lett., 51, p. 2597Amarante, G.W., Benassi, M., Pascoal, R.N., Eberlin, M.N., Coelho, F., (2010) Tetrahedron, 66, p. 4370Silveira, G.P.D., Coelho, F., (2005) Tetrahedron Lett., 46, p. 6477Reddy, L.J., Fournier, J.F., Reddy, B.V.S., Corey, E.J., (2005) Org. Lett., 7, p. 2699Almeida, W.P., Coelho, F., (2003) Tetrahedron Lett., 44, p. 937Feltrin, M.A., Almeida, W.P., (2003) Synth. Commun., 33, p. 1141Dunn, P.J., Fournier, J.F., Hughes, M.L., Searle, P.M., Wood, A.S., (2003) Org. Proc. Res. Dev., 7, p. 244Rossi, R.C., Coelho, F., (2002) Tetrahedron Lett., 42, p. 2797Mateus, C.R., Coelho, F., (2005) J. Braz. Chem. Soc., 16, p. 386Iwabuchi, Y., Furukawa, M., Esumi, T., Hatakeyama, S., (2001) Chem. Commun., p. 2030Masunari, A., Ishida, E., Trazzi, G., Almeida, W.P., Coelho, F., (2001) Synth. Commun., 31, p. 2127Amarante, G.W., Benassi, M., Milagre, H.S.M., Braga, A.A.C., Maseras, F., Eberlin, M.N., Coelho, F., (2009) Chem. Eur. J., 15, p. 12460McCauley, J.A., Nagasawa, K., Lander, P.A., Mischke, S.G., Semones, M.A., Kishi, Y., (1998) J. Am. Chem. Soc., 120, p. 7647De Fatima, A., Pilli, R.A., (2003) Tetrahedron Lett., 44, p. 8721Abella, C.A.M., Rezende, P., Lino De Souza, M.F., Coelho, F., (2008) Tetrahedron Lett., 49, p. 145Mengel, A., Reiser, O., (1999) Chem. Rev., 99, p. 1191Nicolaou, K.C., Baran, P.S., Zhong, Y.L., Barluenga, S., Hunt, K.W., Kranich, R., Vega, J.A., (2002) J. Am. Chem. Soc., 10, p. 2233Nicolaou, K.C., Casey, J.N.M., Montagnon, T., (2004) J. Am. Chem. Soc., 16, p. 5192Corey, E.J., Palani, A., (1995) Tetrahedron Lett., 44, p. 795Crone, B., Kirsch, S.F., (2006) Chem. Commun., 7, p. 764Goddard Iii, W.A., Su, J.T., (2005) J. Am. Chem. Soc., 127, p. 14146Ramadhar, T.R., Batey, R.A., (2011) Synthesis, p. 1321Xu, L.W., Li, L., Lai, Q.G., Jiang, J.X., (2011) Chem. Soc. Rev., 40, p. 1777Pige, F.C., (2010) Synthesis, p. 1745Tietze, L.F., Kinzel, T., Brazel, C.C., (2009) Acc. Chem. Res., 42, p. 367Lu, Z., Ma, S.M., (2008) Angew. Chem., Int. Ed., 47, p. 258De Fatima, A., Robello, L.G., Pilli, R.A., (2006) Quím. Nova, 29, p. 1009Ramon, D.J., Yus, M., (2006) Chem. Rev., 106, p. 2126Beletskaya, I., Moberg, C., (2006) Chem. Rev., 106, p. 2320Trost, B.M., Jiang, C.H., (2006) Synthesis, p. 369Cherest, N., Felkin, H., Prudent, N., (1968) Tetrahedron Lett., 18, p. 2199Anh, N.T., (1980) Top. Curr. Chem., 88, p. 146Evans, D.A., Dart, M.J., Duffy, J.L., Yang, M.G., (1996) J. Am. Chem. Soc., 118, p. 4322Chauvin, Y., (2006) Angew. Chem., Int. Ed., 45, p. 3741Hartwig, J.F., (2009) Organotransition Metal Chemistry: From Bonding to Catalysis, , University Science Books SausalitoSchrock, R.R., (1988) Top. Organomet. Chem., 1, p. 1Grubbs, R.H., Chang, S., (1988) Tetrahedron, 54, p. 4413Grubbs, R.H., (2001) Acc. Chem. Res., 34, p. 18Trnka, T.M., Morgan, J.P., Sanford, M.S., Wilhelm, T.E., Scholl, M., Choi, T.L., Ding, S., Grubbs, R.H., (2003) J. Am. Chem. Soc., 125, p. 2546Tori, M., Sato, M., Kondoh, M., Kawase, M., Suzuki, S., Sono, M., Ando, K., Nakashima, K., (2007) Bull. Chem. Soc. Jpn., 2, p. 38

Total synthesis of ('+ or -')- 2-amino- 1,3-propanediols and the styryl-lactones ('+ or -')- Leiocarpin A and ('+ or -')- Goniodiol

Orientador: Fernando Antonio Santos CoelhoDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de QuímicaResumo: Nesse trabalho, apresentamos duas novas aplicações para a reação de Morita-Baylis-Hillman (MBH). Inicialmente, adutos de MBH foram usados na preparação diastereosseletiva de diferentes 2-amino-1,3-propanodióis substituídos. Substâncias que apresentam esse padrão estrutural vem sendo recentemente utilizadas com sucesso como intermediários para a síntese de substâncias com elevado valor farmacológico e sintético. Baseado nesse fato, 2-amino-1,3-propanodióis com estereoquímica relativa anti foram facilmente sintetizados através de uma aminação redutiva de sistemas 2-oxo-1,3-propanodióis derivados de adutos de MBH. A diastereosseletividade observada na etapa de aminação redutiva foi indiretamente confirmada conduzindo os 2-amino-1,3-propanodióis à síntese de oxazolidin-2-onas. A fim de inferir a estereoquímica relativa das oxazolidin-2-onas foram usados experimentos de RMN baseados no efeito nuclear Overhauser (nOe), e também comparação com dados anteriormente publicados na literatura. Além desse trabalho, apresentamos também a síntese total da (±)-Leiocarpina A e do (±)-Goniodiol. Esses produtos naturais pertencem a classe das estiril-lactonas, uma nova classe de substâncias que foram isoladas de plantas do gênero Goniothalamus. Essas estiril-lactonas apresentam comprovada citotoxicidade e seletividade contra diversos tipos de células tumorais humanas. Em uma estratégia direta, um aduto de MBH foi utilizado como precursor para a síntese de um intermediário comum, um dissililoxialdeído, que por sua vez foi utilizado na síntese dos dois produtos naturais, a (±)-Leiocarpina A e o (±)-Goniodiol. Por fim, uma etapa de alilação seletiva nos permitiu apresentar também a síntese total diastereosseletiva da (±)-Leiocarpina AAbstract: We report herein new synthetic applications of the Morita-Baylis-Hillman (MBH) reaction. Initially, we have described a new diastereoselective approach to substituted 2-amino-1,3-propanediols from MBH adducts. These structural moieties have been widely used as intermediates of several compounds with relevant pharmacological and synthetic interests. In this work, 2-amino-1,3-propanediols with anti relative stereochemistry were readily prepared via reductive amination of 2-oxo-1,3-propanediols MBH adducts derivatives. The diastereoselectivity of the reductive amination step was indirectly confirmed as leading the synthesis of oxazolidin-2-ones cores. In order to establish the relative stereochemistry of these oxazolidin-2-ones, NMR experiments, based on nuclear Overhauser effect (nOe), and comparison with the literature data, were successfully performed. We have also reported a total synthesis of (±)-Leiocarpin A and (±)-Goniodiol. These natural products belong to the class of styryl-lactones, a new type of interesting substances which have been isolated from Goniothalamus genus of plants. These compounds present potential citotoxicity and selectivity against different types of human tumor cells. In a straightforward strategy, a MBH adduct proceeded a common intermediate, disilyloxyaldehyde, that resulted in the target compounds, (±)-Leiocarpin A and (±)-Goniodiol. Finally, we described a diastereoselective synthesis of (±)-Leiocarpin A based on a selective allylation reactionMestradoQuimica OrganicaMestre em Químic

Diastereoselective synthesis of substituted 2-amino-1,3-propanediols from Morita-Baylis-Hillman adducts

We report herein a new diastereoselective approach to substituted 2-amino-1,3-propanediols with anti relative stereochemistry from Morita-Baylis-Hillman (MBH) adducts. These structural moieties have been used as intermediates for the synthesis of several compounds with relevant pharmacological and commercial interest. In this strategy, substituted anti 2-amino-1,3-propanediols were readily prepared via ozonolysis of allylic diols obtained from MBH adducts, followed by a diastereoselective reductive amination of the substituted 2-oxo-1,3-propanediols. To demonstrate the synthetic utility of these aminodiols, they were transformed into substituted oxazolidin-2-ones, which were also used in the indirect determination of the relative stereochemistry of the aminodiols.Descrevemos nesse artigo uma abordagem diastereosseletiva, a partir de adutos de Morita-Baylis-Hillman (MBH), para a preparação de sistemas 2-amino-1,3-propanodióis substituídos com estereoquímica relativa anti. Estas unidades estruturais têm sido utilizadas como intermediárias para a síntese de diversas substâncias de interesse farmacológico e comercial. Nessa estratégia, os anti 2-amino-1,3-propanodióis foram facilmente preparados por ozonólise de dióis alílicos obtidos de adutos de MBH, seguido de uma aminação redutiva diastereosseletiva dos 2-oxo-1,3-propanodióis. Para demonstrar a utilidade desses aminodióis, eles foram transformados em oxazolidin-2-onas substituídas, que também foram utilizadas na determinação indireta da configuração relativa dos aminodióis.285293Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Catalytic Enantioselective Synthesis of Allylic Boronates Bearing a Trisubstituted Alkenyl Fluoride and Related Derivatives

The first catalytic method for diastereo- and enantioselective synthesis of allylic boronates bearing a Z-trisubstituted alkenyl fluoride is disclosed. Boryl substitution is performed with either a Z- or E-allyldifluoride and is catalyzed by bisphosphine/Cu complexes, affording products in up to 99 % yield with >98:2 Z/E selectivity and 99:1 enantiomeric ratio. A variety of subsequent modifications are feasible, and notable examples are diastereoselective additions to aldehydes/aldimines to access homoallylic alcohols/amines containing a fluorosubstituted stereogenic quaternary center

Catalytic Enantioselective Synthesis of Amino Skipped Diynes

The Cu-catalyzed synthesis of nonracemic 3-amino skipped diynes via an enantiodetermining C–C bond formation is described using StackPhos as ligand. Despite challenging issues of reactivity and stereoselectivity inherent to these chiral skipped diynes, the reaction tolerates an extremely broad substrate scope with respect to all components and provides the title compounds in excellent enantiomeric excess. The alkyne moieties are demonstrated here to be useful synthetic handles, and 3-amino skipped diynes are convenient building blocks for enantioselective synthesis