Examination of nature's favorite molecules reveals a striking preference for making carbon-heteroatom bonds over carbon-carbon bonds-surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon-heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C-C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C-X-C), an approach we call "click chemistry". Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect "spring-loaded" reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820010601%2940%3A11%3C2004%3A%3AAID-ANIE2004%3E3.0.CO%3B2-5

Click Chemistry: Diverse Chemical Function from a Few Good Reactions.

/pdf/aryl-aryl-bond-formation-one-century-after-the-discovery-of-1jdyxlkwix.pdf

Aryl-aryl bond formation one century after the discovery of the Ullmann reaction.

Although fire is now rarely used in synthetic chemistry, it was not until Robert Bunsen invented the burner in 1855 that the energy from this heat source could be applied to a reaction vessel in a focused manner. The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction. In the past few years, heating and driving chemical reactions by microwave energy has been an increasingly popular theme in the scientific community. This nonclassical heating technique is slowly moving from a laboratory curiosity to an established technique that is heavily used in both academia and industry. The efficiency of "microwave flash heating" in dramatically reducing reaction times (from days and hours to minutes and seconds) is just one of the many advantages. This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.200400655

Controlled microwave heating in modern organic synthesis.

3.7. Palladium Nanoparticles as Catalysts 888 3.8. Other Transition-Metal Complexes 888 3.9. Transition-Metal-Free Reactions 889 4. Applications 889 4.1. Alkynylation of Arenes 889 4.2. Alkynylation of Heterocycles 891 4.3. Synthesis of Enynes and Enediynes 894 4.4. Synthesis of Ynones 896 4.5. Synthesis of Carbocyclic Systems 897 4.6. Synthesis of Heterocyclic Systems 898 4.7. Synthesis of Natural Products 903 4.8. Synthesis of Electronic and Electrooptical Molecules 906

https://www.chem.ccu.edu.tw/~joyce/referance/ericyang/Chem.%20Rev/Chem.%20Rev.%202007,%20107,%20874-922.pdf

The Sonogashira Reaction: A Booming Methodology in Synthetic Organic Chemistry†

A wide array of forms of palladium has been utilized as precatalysts for Heck and Suzuki coupling reactions over the last 15 years. Historically, nearly every form of palladium used has been described as the active catalytic species. However, recent research has begun to shed light on the in situ transformations that many palladium precatalysts undergo during and before the catalytic reaction, and there are now many suggestions in the literature that narrow the scope of types of palladium that may be considered true “catalysts” in these coupling reactions. In this work, for each type of precatalyst, the recent literature is summarized and the type(s) of palladium that are proposed to be truly active are enumerated. All forms of palladium, including discrete soluble palladium complexes, solid-supported metal ligand complexes, supported palladium nano- and macroparticles, soluble palladium nanoparticles, soluble ligand-free palladium, and palladium-exchanged oxides are considered and reviewed here. A considerable focus is placed on solid precatalysts and on evidence for and against catalysis by solid surfaces vs. soluble species when starting with various precatalysts. The review closes with a critical overview of various control experiments or tests that have been used by authors to assess the homogeneity or heterogeneity of catalyst systems.

On the Nature of the Active Species in Palladium Catalyzed Mizoroki–Heck and Suzuki–Miyaura Couplings – Homogeneous or Heterogeneous Catalysis, A Critical Review

The asymmetric organocatalytic conjugate addition of nucleophiles to Michael acceptors is reviewed. Herein an overview of the most important developments and concepts of this flourishing area of catalysis organized by the type of nucleophile involved in the process is reported.

Organocatalytic asymmetric conjugate additions

The mechanism of the Ru(arene)(amino alcohol)-catalyzed transfer hydrogenation of ketones using isopropyl alcohol as the hydrogen source has been studied by means of hybrid density functional methods (B3PW91). Three mechanistic alternatives were evaluated, and it was shown that the reaction takes place via a six-membered transition state, where a metal-bound hydride and a proton of a coordinated amine are transferred simultaneously to the ketone. Further calculations provided a general rationale for the rate of the reaction by comparison of steric effects in the ground and transition states of the ruthenium hydride complex. It was found that the TS has a strong preference for planarity, and this in turn is dependent on the conformational behavior of the O,N-linkage of the amino alcohol ligand. Finally, a general model, rationalizing the enantioselectivity of the reaction, was developed. Experimental studies of both rate and enantioselectivity were used in order to support the computational results.

Ru(arene)(amino alcohol)-Catalyzed Transfer Hydrogenation of Ketones: Mechanism and Origin of Enantioselectivity

Oxime Palladacycles: Stable and Efficient Catalysts for Carbon-Carbon Coupling Reactions.

Oxime-derived chloro-bridged palladacycles 12 and 13 are efficient complexes for the Suzuki−Miyaura reactions of aryl-, allyl-, and benzyl halides with arylboronic acids. The isolated catalysts are thermally stable, not sensitive to air or moisture, and easily accessible from inexpensive starting materials. The reaction can be performed under aerobic conditions with aryl bromides and chlorides, displaying turnover numbers (TON) of up to 5 × 105 and turnover frequencies (TOF) of up to 198 000 h-1 for aryl bromides. Aryl chlorides undergo the Suzuki reaction with arylboronic acids with TON of up to 4700 and TOF up to 4700 h-1. Even inexpensive and readily available benzyl and allyl chlorides undergo the coupling reaction with good turnover numbers. Complexes of 12 catalyze the syntheses of symmetrical biaryls in good yields via reductive coupling of iodoarenes in the presence of Hunig's base.

Highly Active Oxime-Derived Palladacycle Complexes for Suzuki−Miyaura and Ullmann-Type Coupling Reactions

Oxime-derived palladacycles are very efficient and versatile pre-catalysts for a wide range of carbon–carbon bond coupling reactions in air, under very low loading conditions, and employing reagent-grade chemicals. This tutorial review presents the main achievements, advantages and limitations of oxime palladacycles as a source of highly active palladium nanoparticles for high-turnover catalyzed Heck, as well as other homo- and cross-coupling reactions usually carried out employing organic or aqueous solvents. Comparison with other ligandless Pd(II) catalysts is also presented. Recent advances to develop supported oxime-derived palladacycles in order to facilitate precatalyst recovery and reuse in cross-coupling reactions, especially under aqueous reaction conditions, are also discussed.

Diego A. Alonso

Papers

Organocatalytic asymmetric conjugate additions

Ru(arene)(amino alcohol)-Catalyzed Transfer Hydrogenation of Ketones: Mechanism and Origin of Enantioselectivity

Oxime Palladacycles: Stable and Efficient Catalysts for Carbon-Carbon Coupling Reactions.

Highly Active Oxime-Derived Palladacycle Complexes for Suzuki−Miyaura and Ullmann-Type Coupling Reactions

Oxime-derived palladacycles as source of palladium nanoparticles.