Volume 85, Issue 6

The 19th International Conference on Organic Synthesis (ICOS-19) was jointly held with the 24th Royal Australian Chemical Institute Organic Division Conference (RACIOrganic24) in Melbourne, Australia from 1 to 6 July 2012. The meeting was co-chaired by Prof. Mark Rizzacasa (ICOS-19 Chair) from the University of Melbourne and Dr. Paul Savage (RACIOrganic24 Chair) from CSIRO Materials Science and Engineering, Melbourne. This meeting was attended by over 500 scientists from more than 30 countries, making it the largest organic chemistry conference ever to be held in Australia. The extensive program consisted of 12 plenary lectures, 18 invited lectures, the Thieme-IUPAC Prize in Synthetic Organic Chemistry award address delivered by Prof. Melanie Sanford (University of Michigan), and the Birch Medal address given by Prof. Stephen Pyne (University of Wollongong). In addition, there were 60 seminars in the RACIOrganic24 program delivered in 3 parallel sessions and over 240 poster presentations. ICOS-19 topics included the total synthesis of natural products, asymmetric synthesis, organocatalysis, transition- metal catalysis, CH functionalization, new reagents and reactions, prospects in bioorganic chemistry and chemical biology, and the synthesis of organic materials. The 12 papers in this issue of Pure and Applied Chemistry are contributions from both plenary and invited speakers and represent a good cross-section of the themes of this meeting. The tradition will continue in 2014 with the 20th International Conference on Organic Synthesis (ICOS-20), which will be held in Budapest, Hungary. Mark A. Rizzacasa Conference Editor

Intramolecular cycloadditions of bicyclo[1.1.0]butylalkyl-amines represent a rich source of novel heterocyclic scaffolds. As a function of the side chain attached to the amine, formal ene- or [2 + 2] cycloaddition products can be obtained in moderate to high yields. By suitable further functionalizations, a library of 3-azatricyclo[5.1.1.0 1,5 ]-nonanes was prepared and interrogated in 450 biological assays. This discovery collection was found to generate high hit rates and yet the individual samples demonstrated sufficient selectivity to fulfill robust lead criteria. These applications of bicyclo[1.1.0]butanes demonstrate that new synthetic chemistry and novel architectures are promising starting points for the generation of high-value discovery libraries.

Different reactivities and selectivities are observed in water compared with those in organic solvents. In this article, such three examples are described. While ammonia was known not to react in metal-catalyzed allylic amination, palladium-catalyzed allylic amination using aqueous ammonia proceeded to afford primary amines in high yields. Second, allylboronates reacted with aldehydes in aqueous media to afford α-addition adducts exclusively in high yields with high diastereo- and enantioselectivities using Zn(OH) 2 with ligands as catalysts. Finally, it was found that catalytic use of In(0) was effective for the reactions of allylboronates with ketones in water.

Polyketides are a very diverse family of natural products with an extremely broad range of biological activities and pharmacological properties, including antiproliferative, antibiotic, antifungal, or antiplasmodial activities, and in many cases specific targets are addressed at the molecular level. Their structures are characterized by diverse assemblies of methyl- and hydroxyl-bearing stereogenic centers enabling large numbers of stereochemical permutations, which are often embedded into macrolide rings. This complexity renders the stereochemical assignment and directed total synthesis challenging tasks. Within this review, we will detail practicable approaches for the stereochemical determination of diverse complex polyketides of myxobacterial origin by using computational and NMR methods in combination with novel procedures based on bioinformatics. Furthermore, we have developed efficient preparative strategies for the synthesis of these compounds, which have culminated in several first total syntheses. Key aspects of these various endeavors, which will also focus on the importance of conformational bias in complex polyketide analysis and synthesis, will be discussed within this review in the realm of the potent macrolide antibiotics etnangien and rhizopodin. Along these lines, we will also summarize novel methods for the rapid assembly of key structural elements of polyketides including a novel domino concept relying on a combination of a nucleophilic addition and a Tsuji–Trost reaction.

Asymmetric Tsuji–Trost allylation is one of the key chiral technologies for construction of pharmaceutically important compounds because of the high utility of alkenyl-substituted products. Particularly, the dehydrative system using allylic alcohols and protic nucleophiles has started to attract the attention of organic synthetic chemists from the viewpoints of atom and step economy, environmental benignity, and operational simplicity. In this paper, two types of new chiral CpRu catalysts, which have been developed on the basis of redox-mediated donor–acceptor bifunctional catalyst (RDACat) concept, are presented. Complementary use of the chiral catalysts has realized the syntheses of a wide rage of carbocyclic compounds, saturated N - or O -heterocyclic compounds with high reactivity, regioselectivity, enantioselectivity, productivity, and generality.

This review focuses on recent synthetic efforts by our group towards spirastrellolide A methyl ester, a complex marine macrolide containing two spiroacetal ring systems that shows promising anticancer properties . The evolution of a flexible, modular strategy leading to the first total synthesis of (+)-spirastrellolide A methyl ester, and the associated challenges overcome, are highlighted, particularly in dealing with the initial structural ambiguities. This work enabled the development of an improved second-generation synthesis, which revealed a critical dependence of the key macrolactonization step on the nature of the protecting groups in the linker region between the spiroacetal motifs.

Trimethylzincate is known to react through conjugate addition to α,β-unsaturated ketones, but adds much faster to α,β-unsaturated esters at low temperatures. Since the intermediate zinc enolate behaves differently from that of dimethylcuprate, it offers scope for application in a partial synthesis of gibberellin A 3 . A second example involving vinylsulfones having an oxygen atom on the γ-carbon strongly directs incoming nucleophiles in conjugate addition mode. Heteroatom-directed conjugate addition (HADCA) provides very reactive carbanion intermediates leading to cyclobutane ring formation, necessary for synthesis of solanoeclepin A. An alternative reaction for the four-membered carbocyclic ring closure was explored to make a bond formation between the propargylic cation of Nicholas type and allyltrimethylsilane nucleophile of Hosomi–Sakurai type. This method allowed a formation of tricyclo[5.2.1.0 1,6 ]decene framework.

For many years, despite a rich coordination chemistry, gold (Au) was judged as being catalytically inactive for the formation of carbon–carbon bonds. In mid-1970, few reports demonstrated that Au salts could be very useful reagents to catalyze organic transformations. In recent years, homogeneous catalysis by Au has received considerable attention by the scientific community. It was shown that Au(I) or (III) catalysts are specific and more reactive than most of the other soft Lewis acids such as Hg(II), Cu(II), Pt(II), and Pd(II). Taking advantage of the affinity of cationic phosphine Au complexes to triple bonds, we conceived a Au(I)-catalyzed 6-endo - dig cyclization of cyclic enol ether to prepare bridged and fused bicyclic ketone. Keeping in mind that 5- exo - dig cyclizations can be a competitive process, we surveyed various Au(I) complexes.

The osmium-catalyzed oxidative cyclization of vicinal diols onto proximal olefins to generate 2,5- cis -substituted tetrahydrofurans (THFs) has been exploited as the key step for the construction of several complex THF-containing natural products, namely, the annonaceous acetogenins cis -sylvaticin, sylvaticin, and the excitatory amino acid neo-dysiherbaine A. Recently modified conditions that employ a Lewis acid enable the cyclization to proceed under milder conditions, providing greater tolerance to acid-sensitive functional groups, as demonstrated in two of the syntheses. Flexibility for the construction of 2,5- trans -THFs was demonstrated in the synthesis of sylvaticin by utilization of an intramolecular hydride-shift sequence.

Our various efforts toward the synthesis of a set of novel sugar hybrid scaffolds of several biologically active natural products such as taxol, steroids, β-lactams, and otteliones are presented. We have shown the application of the hybrid approach to design and rapidly generate a library of novel natural product-like compounds, which may have interesting biological features, using metathesis and/or cycloaddition reactions as key steps.

Versatile and chemoselective preparation of substituted oxygenated heterocycles is described. Highly diastereoselective metal-catalyzed syntheses of trans -2,6- and cis -2,6-disubstituted tetrahydropyrans (THPs) are presented, along with an easy one-pot access to various ring size benzoannulated spiroketals.

Our work on the application of the boronic acid Mannich reaction to the synthesis of pyrrolizidine alkaloids is described.

We present herein an overview of our ongoing studies with dendralenes. The first synthetic routes to this fundamental family of compounds have revealed long-hidden secrets in hydrocarbon chemistry and set the scene for synthetic and materials chemistry applications.

This study was conceived to evaluate the global scientific output of secondary organic aerosol (SOA) research over the past 20 years and to assess the characteristics of the research patterns, tendencies, and methods in the papers. Data were based on the online version of Science Citation Index Expanded from 1992 to 2011. Publications referring to SOAs were assessed by distribution of the number of publications and times cited, source categories, source journals, author keywords, KeyWords Plus, and the most cited publications in these years. By synthetic analysis of author keywords, KeyWords Plus, titles, and abstracts, it was concluded that modeling is currently and will at least over the next decade continue to be the predominant research method to validate state-of-the-art knowledge of SOAs, and that the foci of SOA research will be the key precursors terpenes and isoprene, the mechanisms of oxidation and gas-phase reactions, and emission inventories.