Synthesis of 5- and 6-Membered S,O- and S,N-Heterocycles

Significance

An n-Bu₃P-catalyzed tandem Umpolung addition-intramolecular cyclization of bifunctional sulfur pronucleophiles to arylpropiolates to give various heterocycles is reported. The work was stimulated by the authors∏ earlier studies on the phosphine-catalyzed synthesis of dioxygenated heterocycles such as 1,4-dioxane derivatives (F. Taran and co-workers Synthesis 2007, 515). The mechanism of the catalytic cycle, proposed without evidence, starts with the addition of the phosphine to the alkyne, followed by α-addition of the nucleophile. The resulting umpoled adduct undergoes cyclization owing to the close proximity of the second nucleophile. The products, 5- or 6-membered sulfur heterocycles such as 2-iminothiazolidin-4-one derivatives, were obtained in yields ranging from moderate to good; neither Michael-type adduct byproducts nor regioisomers were observed. Aromatic aminothiols as nucleophiles gave poor yields. The substitution on the aryl ring was poorly studied but numerous bifunctional nucleophiles were tested.