Synthesis of Aza-1,2-thiophenophanes by Double Ring Enlargement

Two ring enlargement reactions are used to transform the alicyclic 8-membered allyl 2-oxocyclooctane-1-carboxylate (11) to the 13-membered 10-aza-[11]-(2,3)-thiophenophane-1,9-dione (17). The first step yielded the macrocyclic imide allyl N-(3-thienylmethyl)-2,10-dioxo-1-azacyclodecane-3-carboxylate (15) and, after deprotection, N-(3-thienylmethyl)-1-azacyclodecane-2,10-dione (16). In the second step the N-thienyl substituent is incorporated in the large ring by the use of LDA. The overall yield was 45%. This method was also used to convert the 12-membered allyl 2-oxocyclododecane-1-carboxylate (20) to the 17-membered 14-aza-[15]-(2,3)-thiophenophane-1,13-dione (23).