Bicyclic Sultams with a Nitrogen at the Bridgehead and a Sulfur Atom in the Apex Position: Facile Preparation and Conformational Properties

A practical synthesis of bicyclic sultams with a pyramidal bridgehead nitrogen atom and a sulfur atom in the apex position has been elaborated. Compounds with 1-azathiabicyclo[2.2.1]heptane (12a), -bicyclo[3.2.1]octane (12b, 12d), and -bicyclo[3.3.1]nonane (13b) skeletons were obtained by direct twofold inter/intramolecular alkylation of corresponding monocyclic sultams 9 and 10 with α,ω-dihalides 11 in K 2 CO 3 /DMF in 56, 68, 52 and 52 % yield, respectively. On the other hand, a 1-aza-9-thiabicyclo[4.2.1]nonane derivative (12c) could be prepared only by stepwise dialkylation in 24 % overall yield. Structural and conformational properties of four of the newly prepared bicyclic sultams in solution as well as in the solid state are discussed.