The Huisgen 1,3-dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attention in recent years due to the introduction in 2001 of Cu(1) catalysis by Tornoe and Meldal, leading to a major improvement in both rate and regioselectivity of the reaction, as realized independently by the Meldal and the Sharpless laboratories. The great success of the Cu(1) catalyzed reaction is rooted in the fact that it is a virtually quantitative, very robust, insensitive, general, and orthogonal ligation reaction, suitable for even biomolecular ligation and in vivo tagging or as a polymerization reaction for synthesis of long linear polymers. The triazole formed is essentially chemically inert to reactive conditions, e.g. oxidation, reduction, and hydrolysis, and has an intermediate polarity with a dipolar moment of ∼5 D. The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier. In order to understand the reaction in detail, it therefore seems important to spend a moment to consider the structural and mechanistic aspects of the catalysis. The reaction is quite insensitive to reaction conditions as long as Cu(1) is present and may be performed in an aqueous or organic environment both in solution and on solid support.

Cu-catalyzed azide-alkyne cycloaddition.

Introduced to the Market in the Last Decade (2001−2011) Jiang Wang,† María Sańchez-Rosello,́‡,§ Jose ́ Luis Aceña, Carlos del Pozo,‡ Alexander E. Sorochinsky, Santos Fustero,*,‡,§ Vadim A. Soloshonok,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicente Andreś Estelleś, 46100 Burjassot, Valencia, Spain Laboratorio de Molećulas Orgańicas, Centro de Investigacioń Príncipe Felipe, C/ Eduardo Primo Yuf́era 3, 46012 Valencia, Spain Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastian, Spain IKERBASQUE, Basque Foundation for Science, Alameda Urquijo, 36-5 Plaza Bizkaia, 48011 Bilbao, Spain Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska Street 1, 02660 Kyiv-94, Ukraine

Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011).

Secondary organic aerosol (SOA) accounts for a significant fraction of ambient tropospheric aerosol and a detailed knowledge of the formation, properties and transformation of SOA is therefore required to evaluate its impact on atmospheric processes, climate and human health. The chemical and physical processes associated with SOA formation are complex and varied, and, despite considerable progress in recent years, a quantitative and predictive understanding of SOA formation does not exist and therefore represents a major research challenge in atmospheric science. This review begins with an update on the current state of knowledge on the global SOA budget and is followed by an overview of the atmospheric degradation mechanisms for SOA precursors, gas-particle partitioning theory and the analytical techniques used to determine the chemical composition of SOA. A survey of recent laboratory, field and modeling studies is also presented. The following topical and emerging issues are highlighted and discussed in detail: molecular characterization of biogenic SOA constituents, condensed phase reactions and oligomerization, the interaction of atmospheric organic components with sulfuric acid, the chemical and photochemical processing of organics in the atmospheric aqueous phase, aerosol formation from real plant emissions, interaction of atmospheric organic components with water, thermodynamics and mixtures in atmospheric models. Finally, the major challenges ahead in laboratory, field and modeling studies of SOA are discussed and recommendations for future research directions are proposed.

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The formation, properties and impact of secondary organic aerosol: current and emerging issues

Due to their abundance, high strength and stiffness, low weight and biodegradability, nano-scale cellulose fiber materials (e.g., microfibrillated cellulose and bacterial cellulose) serve as promising candidates for bio-nanocomposite production. Such new high-value materials are the subject of continuing research and are commercially interesting in terms of new products from the pulp and paper industry and the agricultural sector. Cellulose nanofibers can be extracted from various plant sources and, although the mechanical separation of plant fibers into smaller elementary constituents has typically required high energy input, chemical and/or enzymatic fiber pre-treatments have been developed to overcome this problem. A challenge associated with using nanocellulose in composites is the lack of compatibility with hydrophobic polymers and various chemical modification methods have been explored in order to address this hurdle. This review summarizes progress in nanocellulose preparation with a particular focus on microfibrillated cellulose and also discusses recent developments in bio-nanocomposite fabrication based on nanocellulose.

Microfibrillated cellulose and new nanocomposite materials: a review

Asymmetric enamine catalysis.

The direct catalytic asymmetric addition of unmodified carbonyl compounds to preformed or in situ-generated imines has emerged as a promising new route to optically enriched alpha- and beta-amino acid derivatives, beta-lactams, and 1,2- and gamma-amino alcohols. The direct catalytic asymmetric Mannich reactions are mediated by small organometallic and organic amine catalysts that can achieve levels of selectivity similar to those possible with natural enzymes. The different small-molecule catalysts described here are complementary in their applications. They also complement each other in syn or anti selectivity of the direct asymmetric Mannich reaction. In this Account, we highlight the recent developments in and contributions to this research.

The direct catalytic asymmetric mannich reaction.

The development of syntheses providing enantiomerically pure α-amino acids has intrigued generations of chemists and been the subject of intense research. This report describes a general approach to functionalized α-amino acids based on catalytic asymmetric synthesis. Proline catalyzed Mannich-type reactions of N-PMP-protected α-imino ethyl glyoxylate with a variety of unmodified ketones to provide functionalized α-amino acids in high yields with excellent regio-, diastereo-, and enantioselectivities. Study of seven examples yielded six with product ee values of ≥99%. In reactions involving ketone donors where diastereoisomeric products could be formed, two adjacent stereogenic centers were created simultaneously upon carbon−carbon bond formation with complete syn-stereocontrol. Significantly, this methodology utilizes readily available and rather inexpensive starting materials, does not require any preactivation of substrates or metal ion assistance, and can be carried out on a gram scale under operation...

A highly enantioselective amino acid-catalyzed route to functionalized α-amino acids

The cooperation and interplay between organic and metal catalyst systems is of utmost importance in nature and chemical synthesis. Here innovative and selective cooperative catalyst systems can be designed by combining two catalysts that complement rather than inhibit one another. This refined strategy can permit chemical transformations unmanageable by either of the catalysts alone. This review summarizes innovations and developments in selective organic synthesis that have used cooperative dual catalysis by combining simple aminocatalysts with metal catalysts. Considerable efforts have been devoted to this fruitful field. This emerging area employs the different activation modes of amine and metal catalysts as a platform to address challenging reactions. Here, aminocatalysis (e.g., enamine activation catalysis, iminium activation catalysis, single occupied molecular orbital (SOMO) activation catalysis, and photoredox activation catalysis) is employed to activate unreactive carbonyl substrates. The trans...

Combinations of Aminocatalysts and Metal Catalysts: A Powerful Cooperative Approach in Selective Organic Synthesis.

Direct Catalytic Intermolecular α‐Allylic Alkylation of Aldehydes by Combination of Transition‐Metal and Organocatalysis

This report describes the unprecedented use of unmodified aldehydes as donors in a catalytic asymmetric Mannich-type reaction. The proline-catalyzed reaction of N-PMP-protected α-imino ethyl glyoxylate with unmodified aliphatic aldehydes provided a general and very mild entry to either enantiomer of β-amino and α-amino acids and derivatives in high yield and stereoselectivity. Six of the seven aldehydes studied yielded products with ee values of 99% or greater. The diastereoselectivity of the reaction increased with the bulkiness of the substituents of the aldehyde donor in the order R = Me < Et < i-Pr < n-Pent. In five of the cases studied, excellent syn stereoselectivities were achieved. In addition, the corresponding chiral β-amino aldehyde adducts can be readily converted to the corresponding amino acid derivatives. Most significantly, this approach provides facile access to substituted β-lactams.

Armando Córdova

Papers

The direct catalytic asymmetric mannich reaction.

A highly enantioselective amino acid-catalyzed route to functionalized α-amino acids

Combinations of Aminocatalysts and Metal Catalysts: A Powerful Cooperative Approach in Selective Organic Synthesis.

Direct Catalytic Intermolecular α‐Allylic Alkylation of Aldehydes by Combination of Transition‐Metal and Organocatalysis

A Highly Enantioselective Route to Either Enantiomer of Both α- and β-Amino Acid Derivatives