1,3-Dipolar cycloaddition of azomethine ylides to carbon(60) and carbon(70): Combinatorial synthesis of a small library of pyridazines using polymer-bound azodicarboxylate resin.

摘要

Azomethine ylides generated from amino acids and aldehydes were reacted with C₆₀ and C₇₀ to give pyrrolidine-fused products—fulleropyrrolidines. A number of 2,5-disubstituted fulleropyrrolidines could be easily generated through this method. The structure assignment of cis versus trans isomeric products of C₆₀ fulleropyrrolidine was definitively achieved by distinguishing between stereoisomeric 2,5-disubstituted fulleropyrrolidines by reaction with a chiral isocyanate as well as CD analysis. The absolute configuration assignment of each isomer was based on a proposed sector rule for chiral fullerene derivatives, where asymmetric perturbation was caused by the attached chiral group. Due to the lower symmetry of C₇₀, the same azomethine ylide reaction produces more stereoisomers. The structure assignment of these C₇₀ fulleropyrrolidine adducts was achieved by the application of a new NMR technology-3He NMR. Based on the relative heights of 3He NMR signals of the crude reaction mixtures, in the azomethine ylide reaction to C₇₀, the reactivity toward bond-1 and bond-2 was generally found to be 55/45. This decreased chemo selectivity toward bond-1 and bond-2 compared with other cycloaddition reactions (such as Diels-Alder, 1,3-dipolar nitrile oxide addition) is ascribed to the more reactive nature of azomethine ylide 1,3-dipole.; Polymer-bound hydrazide resin that has been used in solid phase peptide synthesis was reevaluated as a useful polymeric support in the field of solid phase organic synthesis and combinatorial chemistry. A number of transformations based on this hydrazide resin were carried out on solid support. In particular, the azodicarboxylate resin, which was prepared by reacting hydrazide resin with chloroformates followed by oxidation, was proven to be useful in the combinatorial synthesis of small organic molecules. In a sample study, a small library of pyridazines was prepared by parallel synthesis. Each individual library member product was analyzed by LC-MS.