Unsymmetric 1,3-diynes were synthesized by using bromoallenes as the starter substrates over the catalysts of CuI and amino acid. l-Proline was chosen as the amino acid as a suitable ligand of CuI. Inorganic bases, especially Cs2CO3, obviously facilitated the reaction. After screening the reaction solvents, such as CH2Cl2, DMF, Et2O, C6H5CH3, THF, CH3CN, DMSO and CH3C(O)CH3, DMSO was chosen as the best reaction solvent, and within the solvent, the yield of unsymmetric 1,3-diynes could achieve the good value of 72%. Under optimum conditions of CuI/l-proline, Cs2CO3 and DMSO, bromoallenes with methyl-, bromo- or chloro-groups in the para-position of aromatic rings gave more than 61% yields of unsymmetric 1,3-diynes. When bromoallenes had the ortho- or meta-bromine groups, the reaction failed and there were no products. The mechanism of formation of unsymmetric 1,3-diyne was also proposed as both processes of isomerization and subsequent elimination, which were catalyzed by the coupling of CuI with l-proline.
Scheme 1 Graphic abstract for the synthesis of unsymmetric 1,3-diynes