Palladium- and copper-catalyzed highly selective mono-coupling between 2,6-diiodoanisoles and terminal alkynes in the production of alkynylated anisoles as potential precursors of benzo[b]furans

The coupling reaction between 2,6-diiodoanisoles and terminal alkynes using Pd(PPh3)2Cl2 and CuI as catalysts and diisopropylamine as base in toluene at room temperature for 12 h produced selectively alkynylated 2-iodoanisoles, in good to excellent yields (52-95%), which are useful building blocks with potential application in the synthesis of functionalized benzo[b]furans.A reação de acoplamento entre 2,6-diiodoanisóis e alcinos terminais usando Pd(PPh3)2Cl2 e CuI como catalisadores e diisopropilamina como base em tolueno a temperatura ambiente por 12 h produziu seletivamente 2-iodoanisóis aquinilados, em rendimentos de bons a excelentes (52-95%), os quais são blocos de construção úteis com potencial aplicação na síntese de benzo[b]furanos funcionalizados.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundacao de Apoio ao Desenvolvimento do EnsinoCiencia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT)Universidade Federal de São Paulo (UNIFESP) Departamento de Ciências Exatas e da TerraUniversidade Federal da Grande Dourados Faculdade de Ciências Exatas e TecnologiaUNIFESP, Depto. de Ciências Exatas e da TerraSciEL

Synthesis of Diiodo-Functionalized Benzo[b] furans via Electrophilic Iodocyclization

An electrophilic iodocyclization reaction involving alkynylated 2-iodoanisoles and molecular iodine in the presence of sodium bicarbonate was developed and diiodo-functionalized benzo[b] furans were obtained in yields from 45 to 99%.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao Univ Fed Grande Dourados, Grp Pesquisa Sintese & Caracterizacao Mol MS, Rua Joao Rosa Goes,1761, BR-79825070 Dourados, MS, BrazilUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Rua Prof Artur Riedel,275, BR-09972270 Diadema, SP, BrazilUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Rua Prof Artur Riedel,275, BR-09972270 Diadema, SP, BrazilWeb of Scienc

Heck-Matsuda arylation in trisubstituted olefins : methodological study and application in meso-hexestrol synthesis

Orientador: Carlos Roque Duarte CorreiaTese (doutorado) - Universidade Estadual de Campinas, Instituto de QuímicaResumo: O presente trabalho teve como objetivo geral o estudo metodológico da reação de Heck-Matsuda em olefinas trissubstituídas assim como sua aplicação sintética. No primeiro capítulo foram desenvolvidas novas reações de arilação de Heck-Matsuda, catalisadas por paládio, empregando alquenóis alílicos trissubstituídos com hidroxilas livres e protegidas com grupos de silício. A metodologia desenvolvida utilizou condições brandas e forneceu as metil cetonas 'alfa',ß-dissubstituídas com rendimentos de moderados a ótimos. A reação se mostrou altamente regiosseletiva, proporcionando apenas um produto de arilação, e altamente diastereosseletiva, formando apenas o isômero anti. A nova reação de arilação redox-relay em éteres de silício demonstrou que a presença da hidroxila não é uma condição única para esse processo ocorrer. Além disso, o potencial sintético do método foi demonstrado com a síntese total do meso-hexestrol em 4 etapas com bom rendimento. No segundo capítulo, esforços foram somados para o desenvolvimento de uma metodologia para reação de Heck-Matsuda enantiosseletiva empregando olefinas trissubstituídas. A partir dos resultados obtidos foi esquematizado a síntese de 7 novos ligantes bidentados N',N' com o grupo fenil na porção quiral. Comparativamente com os ligantes utilizados inicialmente no trabalho, somente um dos ligantes sintetizados forneceu, de forma mais satisfatória, a indução de quiralidade no sistema. As metil cetonas 'alfa'ß-dissubstituídas foram obtidas com rendimentos de bons a moderados e razões enantioméricas moderadasAbstract: The present work had as general objective the methodological study of the Heck-Matsuda reaction in trisubstituted olefins and its synthetic application. In the first chapter, a new methodology for the Heck-Matsuda arylation catalyzed by palladium was developed, employing trisubstituted alkenols with free hydroxyls or protected with silicon groups. The developed methodology used mild conditions and provided 'alpha',ß-disubstituted methyl ketones with moderate to high yields. The reaction was shown to be regioselective, providing only one arylation product, and highly diastereoselective, forming only the anti isomer. The new redox-relay arylation reaction for silyl ethers demonstrated that the presence of the free hydroxyl is not a unique condition for this process to occur. In addition, the synthetic potential of the method was demonstrated with a total synthesis of the meso-hexestrol in 4 steps and good yield. In the second chapter, efforts were made for the development of a enantioselective version of the Heck-Matsuda reaction employing trisubstituted alkenols. From the obtained results, the synthesis of seven new bidentate N',N' ligands with a phenyl group at the chiral portion was schematized. Compared with the ligands tested in other works, only one of the synthesized ligands gave a more satisfactory induction of chirality to the system. The 'alpha',ß-disubstituted methyl ketones were obtained in good to moderate yields and moderate enantiomeric ratiosDoutoradoQuimica OrganicaDoutor em Ciências10639-9FAPES

Synthesis of functionalized benzofurans by iodocyclization reaction of alkynylanisoles

<em>Benzofurans are important synthetic building blocks present in a high number of biologically active natural products, pursuing several medicinal properties. In this context, there is an increasing interest in developing efficient syntheses for this class of compounds. Accordingly, we present in this work our preliminary results involving the iodocyclization reaction of 2-iodo-6-alkynylanisoles, employing molecular iodine under mild conditions, leading to the formation of highly functionalized benzofurans, potential precursors of pharmaceuticals and functional materials.</em

Selective coupling reaction between 2,6-diiodoanisoles and terminal alkynes catalyzed by Pd(PPh3)2Cl2 and CuI

<em>The cross-coupling reaction between aryl halides and terminal alkynes, catalyzed by palladium complexes and copper (I) salts, consists in an efficient synthetic tool for the formation of C-C bonds, resulting in disubstituted acetylenic compounds. Accordingly, in this work we present our preliminary results involving the selective cross-coupling reaction between 2,6-diiodoanisoles and terminal alkynes, catalyzed by Pd(PPh₃)₂Cl₂ and CuI, in the formation of 2-iodo-alkynylanisoles (scheme 1).</em

Water as an Eco-friendly Solvent for Iodination Reactions of Aromatic and Heteroaromatic Compounds

In this review article we have gathered relatively recent publications involving modern methodologies for iodination reactions of aromatic and heteroaromatic compounds using pure water or mixtures containing water as environmentally friendly media.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT)Fundacao Univ Fed Grande Dourados, Fac Ciencias Exatas & Tecnol, BR-79804970 Dourados, MS, BrazilUniv Fed Sao Paulo, Dept Ciencias Exatas & Terra, Setor Quim, BR-09972270 Diadema, SP, BrazilUniv Fed Sao Paulo, Dept Ciencias Exatas & Terra, Setor Quim, BR-09972270 Diadema, SP, BrazilWeb of Scienc

Regioselective and Stereoselective Heck–Matsuda Arylations of Trisubstituted Allylic Alkenols and Their Silyl and Methyl Ether Derivatives To Access Two Contiguous Stereogenic Centers: Expanding the Redox-Relay Process and Application in the Total Synthesis of <i>meso</i>-Hexestrol

Novel palladium-catalyzed redox-relay Heck arylation reactions of trisubstituted allylic alkenols were developed employing silyl and methyl ethers. The reactions proceeded under mild conditions in moderate to high yields in an excellent <i>anti</i> diastereoselectivity to form α,β-disubstituted methyl ketones containing two contiguous stereocenters. The new redox-relay arylations using silyl and methyl ethers of the starting alkenols demonstrate that the presence of a free hydroxyl group is not a sine qua non condition for an effective redox-relay process as previously thought. Deuterium-labeled alkenols <b>2-</b><i><b>d</b></i><b>-10a</b>, <b>2-</b><i><b>d</b></i><b>-10b</b>, and <b>2-</b><i><b>d</b></i><b>-10c</b> permitted tracking the palladium-hydride reinsertion steps in the conversion of the starting free alcohols, silyl, and methyl ethers into the corresponding methyl ketone <b>3-</b><i><b>d</b></i><b>-11a</b>, with >98% deuterium retention. Moreover, the synthetic potential of the method was demonstrated with a straightforward synthesis of the <i>meso</i>-hexestrol in 4 steps, in 41% overall yield from alkenol <b>10a</b>