Herein, we advance our understanding on the divergent reaction pathways that are possible, starting from diazido diethyl malonate (easily generated through the oxidative diazidation of diethyl malonate with iodine and sodium azide in DMSO at room temperature): when treated with amines, diazidated malonamides are rapidly formed, many of which then undergo a formal substitution reaction with alkylamines leading to imino malonamides under basic conditions. Using the established conditions of CuAAC click reactions with terminal alkynes, the diazidated malonamides are alternatively transformed into their corresponding bistriazole derivatives, a reaction that is also achievable with diazido diethyl malonate. We now demonstrate that the malonic diester bistriazoles undergo a smooth decarboxylation in the presence of amines, creating novel bistriazole variants derived from acetamides. All protocols presented herein are experimentally simple and enhance the variety of products obtainable from malonic acid derivatives.

The modular synthesis of 1,3-polyols using a chiral phosphine oxide building block is reported. This versatile building block works in a repetitive way for the stereocontrolled synthesis of a tetraol key intermediate, which serves for the first total synthesis of the potentially anti-inflammatory natural product cryptoconcatone D. A new route toward the chiral building block is also presented: Starting from 2-deoxy-d-ribose, the optimized sequence now makes the use of the building block more attractive to practicing chemists again.

A novel ring expansion based on the readily available 2-azido-2-phenyl-indan-1,3-dione is described. Treatment with primary amines and cesium carbonate in a two-step sequence gives rise to 3-amino-2,3-dihydroisoquinoline-1,4-diones with an unprecedented substitution pattern. The corresponding conversion using amino acid methyl esters leads directly to a novel tricyclic 1,10a-dihydroimidazo-isoquinoline-2,5,10-trione scaffold, a structure that has never been reported before, to the best of our knowledge.