Synthesis of Macrocyclic Lactones via Ring Transformation of 4‐( ω ‐Hydroxyalkyl)‐1,3‐oxazol‐5(4 H )‐ones

The synthesis of α ‐benzamido‐ α ‐benzyl lactones 23 of various ring size was achieved either via ‘direct amide cyclization’ by treatment of 2‐benzamido‐2‐benzyl‐ ω ‐hydroxy‐ N , N ‐dimethylalkanamides 21 in toluene at 90 – 110° with HC l gas or by ‘ring transformation’ of 4‐benzyl‐4‐( ω ‐hydroxyalkyl)‐2‐phenyl‐1,3‐oxazol‐5(4 H )‐ones under the same conditions. The precursors were obtained by C‐alkylations of 4‐benzyl‐2‐phenyl‐1,3‐oxazol‐5(4 H )‐one ( 15 ) with THP ‐ or TBDMS ‐protected ω ‐hydroxyalkyl iodides. Ring opening of the THP ‐protected oxazolones by treatment with Me 2 NH followed by deprotection of the OH group gave the diamides 21 , whereas deprotection of the TBDMS series of oxazolones 25 with TBAF followed by treatment with HC l gas led to the corresponding lactones 23 in a one‐pot reaction.