Enantioselective synthesis of ß-aryl-γ-lactam derivatives via Heck-Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles.

We report herein an enantioselective palladium-catalyzed Heck-Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation followed by a sequential Jones oxidation. The overall method displays a broad scope and good enantioselectivity, favoring the (R) enantiomer. The applicability of the protocol is highlighted by the efficient enantioselective syntheses of the selective phosphodiesterase-4-inhibitor rolipram and the commercial drug baclofen as hydrochloride.

Secondary-sphere modification in proline catalysis: old friend, new connection.

In this work, we exploit our strategy of in situ secondary-sphere modification of organocatalysts to improve the reactivity and selectivity of amino catalysts. Herein, the carboxylic acid moiety of proline was targeted as a site for modification under catalytic reaction conditions with boronic acids. Intermolecular aldol reactions between aromatic aldehydes and cyclopentanone were selected as a proof-of-concept because cyclopentanone as an aldol donor was often associated with decreased selectivity compared to its 6-membered ring analog, hexanone. Our secondary-sphere modification strategy, using naturally occurring L-proline amino acid, enabled reactions at room temperature with high levels of diastereo- and enantio-selectivity and short reaction times. NMR and HR-MS studies shed light on the nature of the catalyst structure and on the role of water in our reactions.

Effect of Solvents on Proline Modified at the Secondary Sphere: A Multivariate Exploration.

The critical influence of solvent effects on proline-catalyzed aldol reactions has been extensively described. Herein, we apply multivariate regression strategies to probe the influence of different solvents on an aldol reaction catalyzed by proline modified at its secondary sphere with boronic acids. In this system, both in situ binding of the boronic acid to proline and the outcome of the aldol reaction are impacted by the solvent-controlled microenvironment. Thus, with the aim of uncovering mechanistic insight and an ancillary aim of identifying methodological improvements, we designed a set of experiments, spanning 15 boronic acids in five different solvents. Based on hypothesized intermediates or interactions that could be responsible for the selectivity in these reactions, we proposed several structural configurations for the library of boronic acids. Subsequently, we compared the statistical models correlating the outcome of the reaction in different solvents with molecular descriptors produced for each of these proposed configurations. The models allude to the importance of different interactions in controlling selectivity in each of the studied solvents. As a proof-of-concept for the practicality of our approach, the models in chloroform ultimately led to lowering the ketone loading to only two equivalents while retaining excellent yield and enantio- and diastereo-selectivity.

Experimental and theoretical studies on gold(III) carbonyl complexes: reductive C,H- and C,C bond formation.

The reactivity of cationic (C^C)gold(iii) carbonyl complexes was investigated. While the in situ-formed IPrAu(bph)CO+ complex (bph = biphenyl-2,2'-diyl) does not undergo a migratory insertion of CO into the neighboring gold-carbon bond, nucleophiles can attack the coordinated CO moiety intermolecularly. Water as a nucleophile initiates a CO2 extrusion combined with a reductive C,H bond formation. The rapid formation of a gold(i) species from an intermediary gold(iii) carbonyl has not been observed before and shows a significant difference in reactivity between (C^C) and (C^N^C)gold(iii) carbonyls. The latter have been reported to form stable gold(iii) hydrides via the WGS reaction. In the case of methanol acting as a nucleophile attacking the gold(iii) carbonyl, no extrusion of CO2 is observed. Instead an intermediary gold(iii) carboxyl complex forms an aryl carboxylate via reductive C-C bond elimination. Experimental and theoretical studies on the mechanism explain the observed selectivities and give new insights into the reactivity of elusive gold(iii) carbonyls.

A General Organocatalytic System for Enantioselective Radical Conjugate Additions to Enals.

Herein, we report a general iminium ion-based catalytic method for the enantioselective conjugate addition of carbon-centered radicals to aliphatic and aromatic enals. The process uses an organic photoredox catalyst, which absorbs blue light to generate radicals from stable precursors, in combination with a chiral amine catalyst, which secures a consistently high level of stereoselectivity. The generality of this catalytic platform is demonstrated by the stereoselective interception of a wide variety of radicals, including non-stabilized primary ones which are generally difficult to engage in asymmetric processes. The system also served to develop organocatalytic cascade reactions that combine an iminium-ion-based radical trap with an enamine-mediated step, affording stereochemically dense chiral products in one-step.

Synthesis of Fulvene Vinyl Ethers by Gold Catalysis.

Gold-catalyzed cyclization of 1,5-diynes with ketones as reagents and solvent provides diversely substituted vinyl ethers under mild conditions. The regioselectivity of such gold-catalyzed cyclizations is usually controlled by the scaffold of the diyne. Herein, we report the first solvent-controlled switching of regioselectivity from a 6-endo-dig- to 5-endo-dig-cyclization in these transformations, providing fulvene derivatives. With respect to the functional-group tolerance, aryl fluorides, chlorides, bromides, and ethers are tolerated. Furthermore, the mechanism and selectivity are put to scrutiny by experimental studies and a thermodynamic analysis of the product. Additionally, 6-(vinyloxy)fulvenes are a hitherto unknown class of compounds. Their reactivity is briefly evaluated, to give insights into their potential applications.

Different Selectivities in the Insertions into C(sp2 )-H Bonds: Benzofulvenes by Dual Gold Catalysis Competition Experiments.

An unprecedented, often almost quantitative access to tricyclic aromatic compounds by dual gold catalysis was developed. This synthetic route expands the scope of benzofulvene derivatives through a C(sp2 )-H bond insertion in easily available starting materials. The insertion takes place with an exclusive chemoselectivity with respect to the competing aromatic C-H positions. A bidirectional synthesis with two competing ortho-aryl C-H bonds in the selectivity-determining step also shows perfect selectivity; this result is explained by a computational investigation of the two conceivable intermediates. The intramolecular competition of two non-equivalent aryl C-H bonds with a benzylic methyl group also showed perfect selectivity.

Perfil hematológico, bioquímico sérico, proteína C reativa e cortisol de ararajubas (Guaroba guarouba) mantidas em cativeiro / Blood profile, serum biochemistry, C-reactive protein and cortisol in golden conures (Guaroba guarouba) in captivity

Objetivou-se determinar os valores hematológicos, bioquímicos séricos, proteína C reativa e cortisol de 14 ararajubas (Guaroba guarouba) clinicamente saudáveis mantidas em cativeiro no zoológico do Parque Estadual de Dois Irmãos Recife/PE. Amostras de sangue foram obtidas da veia jugular com volume médio de 0,8ml, fracionando em duas porções, a primeira depositada em tubo MiniCollect®CE contendo EDTA e a outra tubo com gel separador, para a separação do soro sanguíneo. Os indicadores bioquímicos e PCR foram determinados através do analisador ARCHITECT c8000. O cortisol foi analisado no Cobas E411 da Roche. Para a determinação dos números de eritrócitos e leucócitos, foi utilizada a metodologia da contagem em câmara de Neubauer. O hematócrito foi avaliado pelo método do microhematócrito e a hemoglobina pelo método da cianometahemoglobulina. Para a contagem diferencial de leucócitos, foi utilizada a técnica de Shilling. Os índices hematimétricos (VCM, HCM E CHCM) foram determinados com os valores encontrados na série eritrocítica. Os dados foram caracterizados por dispersão de freqüências, utilizando-se as seguintes medidas de tendência central: Média, desvio-padrão, mediana e percentil de 25 e percentil 75. A determinação de alguns parâmetros como ferro, triglicerídeos, PCR e cortisol foram identificados como sendo pioneiramente referenciados nesta espécie de ave. Os dados são apresentados como sendo de referência para a ararajuba (Guaroba guarouba) criada em cativeiro em condições similares de manejo e higidez e ainda pode contribuir para os trabalhos de conservação ex situ desta espécie.

The aim of this study was to determine the hematological, serum biochemical, C-reactive protein and cortisol 14 clinically healthy golden conures (Guaroba guarouba) kept in captivity at the Zoo of Parque Estadual de Dois Irmãos Recife/PE, Brazil. Blood samples were collected from the jugular vein with an average of 0.8mL and divided into two parts, the first deposited in MiniCollect®EC and the other containing EDTA tube with gel separator for separating blood serum. Biochemical indicators and PCR was determined using the ARCHITECT analyzer c8000. Cortisol was analyzed on the Roche Cobas E411. To determine the number of erythrocytes and leukocytes the methodology of counting in a Neubauer chamber was used. Hematocrit was assessed by using the microhematocrit and hemoglobin for the method of cianometahemoglobulina. For the differential count the Shilling technique was used. The RBC indices (MCV, MCH and MCHC) were determined with values found in the erythrocytic series. The data were characterized by dispersion of frequencies, using the following measures of central tendency: mean, standard deviation, median and percentile 25 and 75 percentile. Parameters such as iron, triglycerides, CRP, and cortisol were identified and referenced in this pioneering species of bird. Data are presented as reference for Guaroba guarouba raised in captivity under similar conditions of management and healthiness and can still contribute to the work of ex situ conservation of this species.