Copper-catalyzed enantioselective conjugate addition of Grignard reagent to non-activated acceptors

As a result of decades of research, it is currently possible to perform catalytic asymmetric conjugate additions of organometallics to many classes of Michael acceptors with excellent enantioselectivities and product yields. However, most of these examples comprise relatively reactive and conventional Michael acceptors. Conjugate additions to unconventional less reactive Michael acceptors such α,β-unsaturated carboxamides, α,β-unsaturated carboxylic acids and quinolines which are of major importance in organic synthesis, are still unreachable despite decades of research in this direction. To solve these long standing problems, we have developed a new strategy based on our previous researches. By combining reactive Lewis acids and Grignard reagents, we have tackled their reactivity issues and enabled their asymmetric conjugated addition reactions. Solving these problems allowed us to obtain a series of interesting chiral molecules that can be used for future transformations and applications

Catalytic enantioselective addition of organometallics to unprotected carboxylic acids

Conjugate addition of organometallics to carbonyl based Michael acceptors is a widely used method that allows the building of new carbon-carbon (C-C) bonds and the introduction of chirality in a single step. However, conjugate additions to the simplest Michael acceptors, namely unprotected, unsaturated carboxylic acids, are considered to be prohibited by the fact that acid-base reactions overpower any other type of reactivity, including nucleophilic addition. Here we describe a transient protecting group strategy that allows efficient catalytic asymmetric additions of organomagnesium reagents to unprotected alpha,beta-unsaturated carboxylic acids. This unorthodox pathway is achieved by preventing the formation of unreactive carboxylate salts by means of a reactive intermediate, allowing modifications of the carbon chain to proceed unhindered, while the stereochemistry is controlled with a chiral copper catalyst. A wide variety of beta-chiral carboxylic acids, obtained with excellent enantioselectivities and yields, can be further transformed into valuable molecules through for instance catalytic decarboxylative cross-coupling reactions

Application of Pedestrian Upstream Detection Strategy in a Mixed Flow Traffic Circumstance

Walking is an environment-friendly trip mode and can help ease the congestion caused by automobiles. Proper design of pedestrian facilities that promotes efficiency and safety can encourage more people to choose walking. Upstream detection (UD) strategy is proposed by previous studies to reduce pedestrian waiting time at mid-block crosswalk (MBC). This paper applied UD strategy to MBC under mixed traffic circumstance where the crosswalk serves both pedestrians and non-motor users. Traffic data was collected from an MBC in the city of Nanjing, China. Simulation models were developed by using the VISSIM software and its add-on module Vehicle Actuated Programming (VAP). The models were categorised by the volume and composition of pedestrians and non-motor users. Models were simulated according to different experimental schemes to explore the effectiveness of the UD strategy under mixed traffic circumstance. T-test and analysis of variance (ANOVA) were used to interpret the simulation results. The main conclusions of this paper are that the UD strategy is still effective at the MBC with a mixed traffic circumstance despite the proportion of non-motor users. However, as the proportion of non-motor users becomes higher, the average delay of pedestrians and non-motor users will increase compared to pure pedestrian flow

Nucleophilic Dearomatization of N-Heteroaromatics Enabled by Lewis Acids and Copper Catalysis

Dearomative functionalization of heteroaromatics, a readily available chemical feedstock, is one of the most straightforward approaches for the synthesis of three-dimensional, chiral heterocyclic systems, important synthetic building blocks for both synthetic chemistry and drug discovery. Despite significant efforts, direct nucleophilic additions to heteroaromatics have remained challenging because of the low reactivity of aromatic substrates associated with the loss of aromaticity, as well the regio- and stereoselectivities of the reaction. Here we present a catalytic system that leads to unprecedented, high-yielding dearomative C-4 functionalization of quinolines with organometallics with nearly absolute regio- and stereoselectivities and with a catalyst turnover number (TON) as high as 1000. The synergistic action of the chiral copper catalyst, Lewis acid, and Grignard reagents allows us to overcome the energetic barrier of the dearomatization process and leads to chiral products with selectivities reaching 99% in most cases. Molecular modeling provides important insights into the speciation and the origin of the regio- and enantioselectivity of the catalytic process. The results reveal that the role of the Lewis acid is not only to activate the substrate toward a potential nucleophilic addition but also to subtly control the regiochemistry by preventing the C-2 addition from happening.</p

Clustering based Multiple Anchors High-Dimensional Model Representation

In this work, a cut high-dimensional model representation (cut-HDMR) expansion based on multiple anchors is constructed via the clustering method. Specifically, a set of random input realizations is drawn from the parameter space and grouped by the centroidal Voronoi tessellation (CVT) method. Then for each cluster, the centroid is set as the reference, thereby the corresponding zeroth-order term can be determined directly. While for non-zero order terms of each cut-HDMR, a set of discrete points is selected for each input component, and the Lagrange interpolation method is applied. For a new input, the cut-HDMR corresponding to the nearest centroid is used to compute its response. Numerical experiments with high-dimensional integral and elliptic stochastic partial differential equation as backgrounds show that the CVT based multiple anchors cut-HDMR can alleviate the negative impact of a single inappropriate anchor point, and has higher accuracy than the average of several expansions