Current Organic Synthesis - Volume 7, Issue 6, 2010

C-C bond forming reactions are currently present in many organic synthetic protocols for the preparation of a plethora of chemical products and intermediates with a wide range of applications in different areas including fragrances, pharmaceuticals, agrochemicals and dyes. The fascinating journey from serendipity to discovery of C-C coupling reactions started in the early 1970s with the first reports of the Suzuki, Heck, Sonogashira and Kumada reactions that were subsequently followed by a series of reports of related processes such as the Stille coupling. Ever since, we have witnessed a continuous and amazing development in importance of such processes in Organic Synthesis. Several protocols, reactions conditions and methodologies have progressed this engaging area of knowledge to limits that scientists would have never dreamt of last century. Heterogeneous catalysts that allow full separation and recycling upon reaction completion, the use of microwave irradiation with short times of reaction (typically minutes), aqueous protocols, efficient and atom-economic reactions that avoid the use of stoichiometric reagents as well as tandem/one-step processes and domino reactions, among others, can be considered as some significant achievements of greener synthetic coupling methodologies reported to date. This special issue, divided in two parts, is dedicated to the latest developments in the areas of C-C and C-Heteroatom couplings in Organic Synthesis. The first part has been devoted to C-C couplings, from the simplest molecules and couplings including model Suzuki, Heck and Sonogashira reactions, to the synthesis of natural products and pharmaceuticals as well as industrial C-C coupling processes. These will include a range of C-C couplings in Organic Synthesis, industrial applications of C-C couplings, active species in the Heck reaction and C-C oxidative couplings. The quality and distribution of the contributions was taken into consideration when inviting worlwide respected and well-known leaders in the field including Profs. Clark (UK), Karimi (Iran) and Lin (Singapur) as well as emerging young researchers such as Drs. Colmenares (Poland) and Iliopoulou (Greece). The editor was delighted to assemble such an outstanding list of contributors for the special issue and would like to thank deeply the authors and the journal for their cooperation and assistance during the past months. There is only one but most important thing left, the readers! The editor sincerely hopes both parts of this special issue will be able to attract the attention of many readers in the field as well as introduce many others in the fascinating world of coupling chemistry and look forward to contemplating further improvements in this area inspired (why not) by some of the contributions included in this issue. With very best wishes for the success of the special issue.

To mitigate the growing production of CO2 (a powerful Green House Gas), the scientific community is taking a step beyond CO2 capture/storage and trying to utilize CO2 for the production of chemicals and fuels. Although a number of organic syntheses using carbon dioxide are known, only a few were applied in industry. The direct carboxylation of organic compounds for the formation of the moieties C-COOH and C-COOR is showed in a convincing way through this paper. Moreover, the huge potential of using of carbon dioxide in the catalytic oxidative coupling of methane to C2 hydrocarbons is also presented. The aim of this review is convey some of the potential methods of carbon dioxide utilization as mild oxidant and reagent in the specific case of C-C coupling reactions. Dedicated to Professor George A. Olah and Professor G.K. Surya Prakash for their significant contribution in CO2 utilization

Carbon-carbon coupling reactions via transition-metal-catalyzed processes have been intensively developed for their important synthetic applications. However, due to both economical and environmental concern, development of novel polymer supported catalysts is of great deal of attention in recent years. The use of these catalysts offers several advantages such as easy workup of the products and recovery of the catalysts. In this paper, recent developments in the Heck, Suzuki and Sonogashira reactions with this type of catalyst are reviewed.

C-C and C-Heteroatom couplings are among the most relevant processes in Organic Synthesis. These reactions can provide access to a wide range of carbon-carbon and carbon-heteroatom scaffolds that find applications in many different areas including agriculture, pharmacy, medicine, cosmetics and natural products. Current society's driving force towards more efficient methodologies (with improved environmental compatibilities at the same time) to meet the requirements of a more sustainable chemical industry, has created the need to search for alternative methodologies to traditionally wasteful and energy intensive protocols that also involve rather complex reaction conditions and media as well as homogeneous transition metal catalysts. In this contribution, we aim to provide an overview of the present and future of greener C-C and C-Heteroatom protocols with selected examples to highlight the latest trends in this field.

Biomass represents the type of renewable energy source that will play a substantial role in the future global energy balance, as it is the only renewable source with the potential to be converted to liquid, solid and gaseous fuels. Today lignocellulosic biomass appears to be the cheapest and most abundant biomass feedstock, yet no economically and technologically feasible process is developed for its conversion to fuels, at least competitive with the currently used petroleum fuels. Biomass pyrolysis is an emerging thermochemical conversion process that leads to the production of bio-oil. Bio-oil however, presents several undesired properties that do not permit its direct exploitation. On the other hand, sugars derived from lignocellulosic biomass make up the predominant class of compounds, also exhibiting undesired properties. In both cases presence of oxygen in biomass derived copounds seems the major problem. Recently the targeted pathways for the conversion of lignocellulose-derived carbohydrates to liquid transportation fuels involve the partial removal of oxygen, CC bond formation of functional molecules, and removal of the remaining oxygen. The formation of C-C bonds between these oxygenated molecules can take place by aldol condensation, alkylation, or ketonization as will be described in the present review study.

This review highlights our studies of the nature of the true catalytic species in the Heck coupling of bromobenzene and styrene with conventionally prepared SiO2-supported Pd particles. Approaches including kinetic test, filtration test and catalyst poisoning were used to probe the behavior and nature of the possible active Pd species in combination with transmission electron microscopy and elemental analysis. We found that the catalytic activity of soluble Pd is suppressed in the presence of the supported Pd particles. Through a study of dependences of reaction rate on Pd loading and on leached Pd concentration, we demonstrated that the leached soluble Pd is responsible for the catalysis irrespectively of the supported Pd particles. With the aid of catalyst poisoning, we further illustrated that Pd clusters are inactive for the homogeneous Heck reaction, molecular Pd being solely active. We also discuss Pd scavenging from solution by solidbound thiols during the Heck reaction. In addition, we propose a ligand-free homogeneous Heck reaction mechanism with the generation of soluble molecular Pd0 by Pd leaching from conventionally prepared supported Pd particles.

Aromatic substitutions are a very important class of reaction for both the fine chemical and pharmaceutical industries. The use of palladium as a catalyst for these types of reactions is common during the research stages of product development. Its desirable criteria include high selectivity, being compatible with many types of functional groups, typical use without protection groups and strong bases, and introduction at relatively late stages of the total synthesis. However, its use is less common in large-scale manufacture due to their cost and availability of aromatic halides at scale. In addition, palladium contamination of pharmaceutical products has to be 10 ppm or less that is difficult to achieve without strenuous and typically wastefully remediation strategies in place. In this contribution, we aim to give an overview of the use of a range of greener methodologies and catalysts trends in C-C couplings at industrial scale, with selected examples of current compounds industrially produced via such reactions.

The structural and synthetic aspects related to α-oxyiminophosphorus derivatives are reviewed. This includes their preparation through reactions involving C-N double bond or P-C single bond formation as well as the O-functionalization or transformations at the phosphorus atom of other phosphorus substituted oximes. Moreover the synthetic features of α-oxyiminophosphorus derivatives include the reduction of the oximo group with selective preparation of biologically active α-amino-phosphonate and -phosphinate derivatives, as well as the oxidative transformations on the oxime group, rearrangement versus fragmentation reactions, radical reactions and formation of metal complexes.

As steric repulsion, the electronic effect of catalysts also plays a crucial role in asymmetric catalysis. The influence of the electronic effect of catalysts on the enantioselectivity in asymmetric catalysis, including metal-chiral ligand complex and organocatalyst systems, was reviewed. The applicability and complexity of the influence were discussed. Rationally tuning the electronic effect of catalysts can indeed improve enantioselectivity. It is one of the important pathways to achieve the best stereoselectivity in asymmetric catalysis.