A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes.

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.

The biaryl structural motif is a predominant feature in many pharmaceutically relevant and biologically active compounds. As a result, for over a century 1 organic chemists have sought to develop new and more efficient aryl -aryl bond-forming methods. Although there exist a variety of routes for the construction of aryl -aryl bonds, arguably the most common method is through the use of transition-metalmediated reactions. 2-4 While earlier reports focused on the use of stoichiometric quantities of a transition metal to carry out the desired transformation, modern methods of transitionmetal-catalyzed aryl -aryl coupling have focused on the development of high-yielding reactions achieved with excellent selectivity and high functional group tolerance under mild reaction conditions. Typically, these reactions involve either the coupling of an aryl halide or pseudohalide with an organometallic reagent (Scheme 1), or the homocoupling of two aryl halides or two organometallic reagents. Although a number of improvements have developed the former process into an industrially very useful and attractive method for the construction of aryl -aryl bonds, the need still exists for more efficient routes whereby the same outcome is accomplished, but with reduced waste and in fewer steps. In particular, the obligation to use coupling partners that are both activated is wasteful since it necessitates the installation and then subsequent disposal of stoichiometric activating agents. Furthermore, preparation of preactivated aryl substrates often requires several steps, which in itself can be a time-consuming and economically inefficient process.

http://aether.cmi.ua.ac.be/artikels/Artikels%20Gitte/Artikels/Reviews/Heck-Type-lautens.pdf

Aryl-aryl bond formation by transition-metal-catalyzed direct arylation.

Green Chemistry is a relatively new emerging field that strives to work at the molecular level to achieve sustainability. The field has received widespread interest in the past decade due to its ability to harness chemical innovation to meet environmental and economic goals simultaneously. Green Chemistry has a framework of a cohesive set of Twelve Principles, which have been systematically surveyed in this critical review. This article covers the concepts of design and the scientific philosophy of Green Chemistry with a set of illustrative examples. Future trends in Green Chemistry are discussed with the challenge of using the Principles as a cohesive design system (93 references).

Green Chemistry: Principles and Practice

http://image.sciencenet.cn/olddata/kexue.com.cn/blog/admin/images/upfiles/2007101622257911935.pdf

The growing impact of click chemistry on drug discovery.

Historical Note, General Principle and Mechanistic Criteria. Nitrile Ylides. Nitrile Oxides and Nitrile Imines. Diazoalkanes. Azides and Nitrous Oxide. Azomethine Ylides. Azomethine Imines. Mesoionic Ring Systems. Nitrones. Azimines, Azoxy Compounds and Nitro Compounds. Ozone and Carbonyl Oxides. Intramolecular Dipolar Cycloadditions. Theory of 1,3--Dipolar Cycloadditions. 1,3--Dipolar Cycloreversions. Higher Order Dipolar Cycloadditions.

1,3-Dipolar Cycloaddition Chemistry

Nitrones (Jason N. Martin and Raymond C. F. Jones). Nitronates (Scott E. Denmark and Jeromy J. Cottell). Azomethine Ylides (L. M. Harwood and R. J. Vickers). Carbonyl Ylides (Mark C. McMills and Dennis Wright). Thiocarbonyl Ylides (Grzegorz Mloston and Heinz Heimgartner). Nitrile Oxides (Volker Jager and Pedro A. Colinas). Nitrile Ylides and Nitrile Imines (John T. Sharp). Diazoalkanes (Gerhard Maas). Azides (Chin-Kang Sha and A. K. Mohanakrishnan). Mesoionic Ring Systems (Gordon W. Gribble). Effect of External Reagents (Shuji Kanemasa). Asymmetric Reactions (Kurt Vesterager Gothelf and Karl Anker Jorgensen). Index.

Albert Padwa

Papers

1,3-Dipolar Cycloaddition Chemistry

Synthetic applications of 1,3-dipolar cycloaddition chemistry toward heterocycles and natural products

Cascade Processes of Metallo Carbenoids

Ylide formation from the reaction of carbenes and carbenoids with heteroatom lone pairs

Synthetic Applications of Furan Diels-Alder Chemistry