Application Of "Click" Chemistry On Multi-Component Reaction And Asymmetric Reaction In Water

"Click" chemistry is a modular approach proposed by Sharpless et al. that uses only the most practical and reliable chemical transformations. The goal is to develop an expanding set of powerful, selective, and modular "blocks" that work reliably in both small- and large-scale applications. The reaction must be modular, wide in scope, give very high yields, generate only inoffensive byproducts that can be removed by nonchromatographic methods, and be stereospecific. The required process characteristics include simple reaction conditions, readily available starting materials and reagents, the use of no solvent or a solvent that is benign or easily removed, and simple product isolation.The copper-(I)-catalyzed 1,2,3-triazole formation from azides and terminal acetylenes is a particularly powerful linking reaction, due to its high degree of dependability, complete specificity, and the bio-compatibility of the reactants. The triazole products are more than just passive linkers; they readily associate with biological targets, through hydrogen bonding and dipole interactions. Its applications are increasingly found in all aspects of drug discovery, ranging from lead finding through combinatorial chemistry and target-templated in situ chemistry, to proteomics and DNA research, using bioconjugation reactions.The development of the copper(I)-catalyzed cycloaddition reaction between azides and terminal alkynes has led to many interesting applications of click reactions including the synthesis of natural product derivatives. Although azides and alkynes display high mutual reactivity, individually these functional groups are two of the least reactive in organic synthesis. They have been termed bioorthogonal because of their stability and inertness towards the functional groups typically found in biological molecules. This bioorthogonality has allowed the use of the azide-alkyne [3+2] cycloaddition in various biological applications including target guided synthesis and activity-based protein profiling.After extensively reviewed, we found both N-substituted and 4- or 5-substituted 1,2,3-trizoles had more potentialapplication than simple 1,2,3-triazole derivatives. The low reactivity of acetylenic amides toward 1,3-dipolar cycloaddition with azides has remained a problem for direct access to biologically active 1,2,3-triazoles with an amide substituent; the preparation of these compounds has generally involved the use of easily available 1,2,3-triazole esters, acids, or imines as intermediates, followed by a functional group transformation to the amide.Herein, we have demonstrated a new three-component protocol of amine, propargyl halide and azide in one-pot procedure for the synthesis of (1 -substituted-1H-1,2,3-triazol-4-ylmethyl)-dialkylamine derivatives in the presence of copper(I) in water. The process showed the considerable synthetic advantages in terms of air, products diversity, mild reaction condition, simplicity of the reaction procedure, and good to excellent yields, can provide an access to a class of compounds that can serve as useful building blocks for synthesis.Past several years, between the extremes of transition metal catalysis and enzymatic transformations, a third approach to the catalytic production of enantiomerically pure organic compounds has emerged—organocatalysis. Proline, a chiral-pool compound which catalyzes aldol and related reactions by iminium ion or enamine pathways, is a prototypical example by List et al.. Amino acid-derived organocatalysts such as the oxazolidinone introduced by MacMillan et al. or the chiral thiourea introduced by Jacobsen et al. have enabled excellent enantioselectivity in, e.g., Diels-Alder reactions ofα,β-unsaturated aldehydes or the hydrocyanation of imines. Overall, asymmetric organocatalysis has matured in recent few years into a very powerful, practical, and broadly applicable third methodological approach in catalytic asymmetric synthesis.Herein, we have developed a series of novel asymmetric pyrrolidine-triazole organocatalysts and demonstrated their potential for Michael reactions with high yields, excellent enantioselectivity, and a very good diastereoselectivity. Overall, we introduced "click" chemistry to the field of asymmetric organocatalysis and extended the application of "click" chemistry. Therefore, Cu(I)-catalyzed 1,3-dipolar "click" azide-alkyne cycloaddition provides the modular and tunable features for the pyrrolidine-triazole catalysts. In addition, it is worthy of noting that the triazole moiety introduced cannot only act as a positive phase tag to complete the reaction in a broad range of solvents, but can also serve as an efficient chiral-induction group to ensure a high selectivity.