Synthesis of an Enantiomerically Pure 1,3‐Thiazole‐5(4H)‐thione and Its Stereoselective 1,3‐Dipolar Cycloaddition with an Azomethine Ylide

Starting from the enantiomerically pure 2H‐azirin‐3‐amines (R,S)‐ 4 and (S,S)‐ 4 , the enantiomeric, optically active 4‐benzyl‐4‐methyl‐2‐phenyl‐1,3‐thiazole‐5(4H)‐thiones (R)‐ 1 and (S)‐ 1 , respectively, have been prepared (Schemes 2 and 3). In each case, the reaction of 1 with N‐(benzylidene)(trimethylsilyl)methyl]amine ( 2 ) in HMPA in the presence of CsF and trimethylsilyl triflate gave a mixture of four optically active spirocyclic cycloadducts (Scheme 4). Separation by preparative HPLC yielded two pure diastereoisomers, e.g., (4R,5R,9S)‐ 10 and (4R,5R,9R)‐ 10 . The regioisomeric compounds 11 were obtained as a mixture of diastereoisomers. The products were formed by a 1,3‐dipolar cycloaddition of 1 with in situ generated azomethine ylide 3 , which attacks 1 stereoselectively from the sterically less‐hindered side, i.e., with (R)‐ 1 the attack occurs from the re‐side and in the case of (S)‐ 1 from the si‐side.