Click Chemistry: Diverse Chemical Function from a Few Good Reactions

Abstract

Beyond the Paradigm of Carbonyl ChemistryLife on Earth requires the construction of carbon ± carbon bonds in an aqueous environment. Carbonyl (aldol) chemistry is natures primary engine of CÀC bond formation. Not only do the requisite carbon electrophiles (carbonyls) and nucleophiles coexist in water, but water provides the perfect environment for proton shuttling among reactants, which is required for reversible carbonyl chemistry.With CO 2 as the carbon source and a few good carbonyl chemistry based reaction themes, nature achieves astonishing structural and functional diversity. Carbonyl chemistry is used to make a modest collection of approximately 35 simple building blocks, which are then assembled into biopolymers. The enzymatic polymers serve, in concert with increments of energy provided by adenosine triphosphate, as selective catalysts which prevent natures carbonyl chemistry based syntheses from collapsing into chaos. Since many biosynthetic pathways require a unique enzyme for each step, the enzymecontrol strategy required a heavy investment of time and resources for catalyst development. With a few billion years and a planet at her disposal, nature has had both time and resources to spare, but we, as chemists on a human timescale, do not.Nevertheless, carbonyl-based reactions have always been profoundly appealing to students and practitioners of organic chemistry. It is our contention that organic synthesis conducted, as it has been, in imitation of natures carbonyl chemistry is ill-suited for the rapid discovery of new molecules with desired properties.Many transformations that form ªnewº carbon ± carbon bonds are endowed with only a modest thermodynamic driving force. In particular, equilibrium ªaldolº reactions are often energetically favorable by less than 3 kcal mol À1 . [1] For these processes to reach completion in the laboratory, an additional ªpushº must be provided, often by application of Le Chateliers principle (for example, azeotropic removal of water), by coupling the desired process to an exothermic coreaction (for example, a strong ªbaseº a strong ªacidº), or by virtue of favorable entropic considerations (such as intramolecular ring closure) without enthalpic penalties (such as formation of strained rings). Thus, due in effect to the loss of one ªequivalentº of ester, resonance stabilization, the first

The btp [2,6-bis(1,2,3-triazol-4-yl)pyridine] binding motif: a new versatile terdentate ligand for supramolecular and coordination chemistry

“…'Click chemistry' is a term first coined by Sharpless and co-workers 65,66 to describe modular, high-yielding reactions which are ideally insensitive to the presence of oxygen and water. The azide-alkyne 1,3-dipolar cycloaddition (or the 1,3-Huisgen reaction 67 ) was identified as the 'cream of the crop' of 'click' reactions.…”

New methodologies in the construction of dendritic materials

“…25 The requirements of a Clickreaction are: (1) robust and quantitative, i.e., the reactions are highly selective and the yields are near 100%: (2) the reactions are able to proceed in the presence of a variety of solvents such as water, organic solvents, etc., irrespective of their protic/ aprotic or polar/non-polar character: (3) high tolerance to other functional groups and (4) the reaction proceeds at various types of interfaces such as solid/liquid, liquid/liquid or even solid/solid. 26 Another advantage of these reactions is the requirement of only stoichiometric amounts of starting materials with virtually no by-products being formed, which greatly simplifies the purification procedures.…”

A simple access to transition metal cyclopropenylidene complexes

“…We chose to test its catalytic activity in the [3+2] cycloaddition of azides and alkynes. 24 The reaction of heptyl azide with phenyl acetylene, under mild conditions (room temperature, solvent-free), using a low catalyst loading was investigated. Comparison with [Cu(Cl)(SIMes)] [SIMes = (N,N'-bis-[2,4,6-(trimethyl)phenyl]imidazolidin-2-ylidene], which represents the state-of-the-art 25 for such a reaction, showed that the cyclopropenylidene complex 2 has a higher catalytic activity than its NHC analogue.…”