Synthesis of Ethyl (2RS,3SR)‐1‐Tosyl‐3‐Vinylazetidine‐2‐carboxylate and ethyl (2RS,E)‐3‐ethylidene‐1‐tosylazetidine‐2‐carboxylate (=rac‐ethyl N‐tosylpolyximate)

The synthesis of 3‐ethylideneazetidine‐2‐carboxylic acid (=polyoximic acid; 3) is a approached in two different ways leading to potential precursors of 3. The first way involved a ring closure to a vinyl‐subsatituted azetidin. Thus, Ireland‐Claisen rearrangement of the Boc‐glycinates 6 and 10 of (Z)‐ and (E)‐2‐butene‐1,4‐diol afforded, after exchange of the N‐protecting groups, the isomeric 2‐(tosylamino)‐3‐vinylbutanolides 13 and 14 with high stereoselectivity. Only the cis‐isomer 14 could be further transformed to 3‐(bromomethyl)‐2‐(tosylamino)‐4‐pentenoate 17, and in a smoth cyclization with K2CO3, to trans‐3‐vinylazetidtene‐2‐carboxylaze 18 (Scheme 2). In the second approach, the 3‐ethylidene isomer 19 of 18 was obtained more directly by a [2+2] cycloaddition, together with the two isomers 23 and 24, from methlallene 20 and (tosyliminno)acetate 21 (Scheme 3). The main product of this reaction was, however, 2‐(tosylamino)‐4‐hexinoate 22, the product of an ene reaction.