Asymmetric 1,3-dipolar cycloadditions of acrylamides

This critical review, which is relevant to researchers in synthetic organic chemistry, focuses on asymmetric 1,3-dipolar cycloadditions with acrylamides. The use of chiral acrylamides as dipolarophiles leads to high levels of stereocontrol, due to conformational constraint in the acrylamides. Employment of chiral tertiary acrylamides containing nitrogen heterocycles is particularly effective in controlling the stereoselectivity. Following a general overview of 1,3-dipolar cycloadditions, the main body of the review focuses on asymmetric 1,3-dipolar cycloadditions of acrylamides with nitrile oxides, nitrones, diazoalkanes and azomethine ylides, with particular emphasis on the rationale for the observed stereocontrol (215 references)

New Conceptual Understanding of Lewis Acidity, Coordinate Covalent Bonding, and Catalysis

The focus of this dissertation is to correct misconceptions about Lewis acidity, uncover the physical nature of the coordinate covalent bond, and discusses how Lewis acid catalysts influence the rate enhancement of the Diels-Alder reaction. Large-scale quantum computations have been employed to explore many of Lewis\u27 original ideas concerning valency and acid/base behavior. An efficient and practical level of theory able to model Lewis acid adducts accurately was determined by systematic comparison of computed coordinate covalent bond lengths and binding enthalpies of ammonia borane and methyl substituted ammonia trimethylboranes with high-resolution gas-phase experimental work. Of all the levels of theory explored, M06-2X/6-311++G(3df,2p) provided molecular accuracy consistent with more resource intensive QCISD(T)/6 311++G(3df,2p) computations. Coordinate covalent bond strength has traditionally been used to judge the strength of Lewis acidity; however, inconsistencies between predictions from theory and computation, and observations from experiment have arisen, which has resulted in consternation within the scientific community. Consequently, the electronic origin of Lewis acidity was investigated. It has been determined that the coordinate covalent bond dissociation energy is an inadequate index of intrinsic Lewis acid strength, because the strength of the bond is governed not only by the strength of the acid, but also by unique orbital interactions dependent upon the substituents of the acid and base. Boron Lewis acidity is found to depend upon both substituent electronegativity and atomic size. Originally deduced from Pauling\u27s electronegativities, boron\u27s substituents determine acidity by influencing the population of its valence by withdrawing electron density. However, size effects manifest differently than previously considered, where greater σ-bond orbital overlap, rather than π-bond orbital overlap, between boron and larger substituents increase the electron density available to boron, thereby decreasing Lewis acidity. The computed electronegativity and size effects of substituents establish unique periodic trends that provide a novel and clearer understanding of boron Lewis acidity, consistent with first principle predictions. Lastly, it is discovered that the energetics associated with the transition structure converge much slower than what was observed for coordinate covalent bonded ground states. Consequently, it is harder to model activation barriers, as compared to binding energies, to within experimental accuracy, because larger basis sets must be employed. Hyperconjugation within dienophile ground states, initiated by geminal Lewis acid interactions, is found to govern the strength of the coordinate covalent bond between the Lewis acid and the dienophile. A novel interpretation is presented where the strength of the coordinate covalent bond within the Lewis acid activated dienophile is governed by donor-acceptor orbital interactions between the π-density present on the carbonyl group to the σ* orbitals on the Lewis acid, rather than the main donor-acceptor motif between the oxygen lone pair and the empty 2p orbital on the Lewis acid. Moreover, the same hyperconjugation within the dienophile controls the rate enhancement of the Lewis acid catalyzed Diels-Alder reaction, by modulating the energy of the dienophile\u27s lowest unoccupied molecular orbital. A new understanding of Lewis acidity and coordinate covalent bonding has been achieved to better describe and predict the structure and electronic mechanism of organic reactions

Síntese selectiva de moléculas com potencial interesse biológico. Desenvolvimento de metodologias sustentáveis

Dissertação apresentada para obtenção do Grau de Doutor em Química Sustentável pela Universidade Nova de Lisboa, Faculdade de Ciências e TecnologiaO conceito de sustentabilidade assumiu, no decorrer da primeira década do Século XXI, um carácter transversal à actividade científica, económica e social. Actualmente, a sociedade contemporânea projecta o seu futuro com base na racionalidade de consumo de recursos e na diminuição do impacte da actividade humana no ambiente, com vista ao desenvolvimento sustentável da comunidade. Este projecto teve como principal objectivo o desenvolvimento de novas metodologias sintéticas sustentáveis na valorização de glúcidos enquanto fonte renovável de biomassa em estratégias de síntese assimétrica. Neste sentido, o projecto foi inspirado em alguns princípios da química verde, nomeadamente na valorização de glúcidos enquanto matéria prima renovável em síntese orgânica, na aplicação de irradiação de microondas como técnica eficiente de aquecimento, na redução e eliminação de consumo de solventes e no controlo estereosselectivo de reacções de cicloadição. Desenvolveu-se um procedimento experimental para a síntese de N-alquilnitronas, na ausência de solvente e sob irradiação de microondas, de entre as quais C-fenil-N-terc-butilnitrona, molécula com elevada notoriedade na indústria farmacêutica pela sua potencial actividade na prevenção de stress oxidativo. Procedeu-se à cicloadição 1,3-dipolar de nitronas a trans-crotonato de etilo na ausência de solvente e sob irradiação de microondas, contribuindo para a redução substantiva do consumo energético do protocolo de cicloadição, reduzindo os tempos de reacção de várias horas em refluxo para apenas cinco minutos de irradiação de microondas. Aplicaram-se derivados insaturados de Dxilopiranose enquanto indutores quirais na cicloadição 1,3-dipolar de nitronas a derivados de éster trans-crotonato, tendo-se obtido elevada regio e estereosselectividade nos cicloaductos obtidos. Optimizou-se um protocolo de glicosilação de ácidos carboxílicos por esterificação de brometo de D-xilopiranosilo sob irradiação de microondas. Esta metodologia foi aplicada na glicosilação de ácidos gordos e de ácidos carboxílicos insaturados, com potencial utilidade enquanto monómeros na síntese de copolímeros biodegradáveis ou em estratégias de indução quiral na síntese assimétrica de produtos naturais. Desenvolveu-se uma síntese breve e eficiente para a preparação de análogos de L-fucopiranose a partir de D-galactopiranose, material de partida disponível comercialmente a baixo custo, como alternativa à utilização de L-(−)-galactose.Fundação para a Ciência e a Tecnologia - SFRH/BD/38204/200

キラルブレンステッド酸触媒による不斉(Hetero-)Diels-Alder反応の開発と立体選択性の向上/逆転の予測と検証

Tohoku University寺田眞浩課

Do secondary orbital interactions really exist?

A revision of the most typical examples used to illustrate the existence of secondary orbital interactions (SOI) has been achieved. However, our analysis indicates that no conclusive evidence can be obtained from these cases. All five examples proposed by Woodward and Hoffmann in The Conservation of Orbital Symmetry have been revisited. A combination of well-known mechanisms (such as solvent effects, steric interactions, hydrogen bonds, electrostatic forces, and others) can be invoked instead to justify the endo/exo selectivity of Diels−Alder reactions.Financial support of the Comisión Interministerial de Ciencia y Tecnología (Project MAT99-1176-C02-01) is acknowledged.Peer reviewe

Stereoselective cycloaddition of 1,3-cyclohexadiene on Si(100): A simple algorithm for product identification based on secondary orbital interactions

We consider the reaction of 1,3-cyclohexadiene (1,3-CHD) on Si(100) and show that the observed reactivity and stereoselectivity cannot be explained on the basis of thermodynamics. We postulate the existence of secondary orbital interactions (SOIs) and introduce a simple algorithm that examines all possible secondary interactions between the frontier orbitals of the molecule and the surface. We demonstrate using an orbital symmetry-based algorithm supported by DFT calculations that SOIs favor a particular molecular configuration, consistent with the experimental observations. The potential role of SOIs in controlling surface chemical reactions is discussed. \ua9 2011 American Chemical Society.Peer reviewed: YesNRC publication: Ye