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

Abstract

The synthesis of a-benzamido-a-benzyl lactones 23 of various ring size was achieved either via 'direct amide cyclization' by treatment of 2-benzamido-2-benzyl-x-hydroxy-N,N-dimethylalkanamides 21 in toluene at 90 -110°with HCl gas or by 'ring transformation' of 4-benzyl-4-(x-hydroxyalkyl)-2-phenyl-1,3-oxazol-5(4H)-ones under the same conditions. The precursors were obtained by C-alkylations of 4-benzyl-2-phenyl-1,3-oxazol-5(4H)-one (15) with THP-or TBDMS-protected xhydroxyalkyl 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 HCl gas led to the corresponding lactones 23 in a one-pot reaction.

Ring size-reactivity relationship in radical ring-opening copolymerisation of thionolactones with vinyl pivalate

“…A computational investigation was carried out in order to provide insight into the relative aptitude of the four different thionolactone monomers, once incorporated as ring-closed radicals at the chain end, to undergo ring opening vs. addition Since we could not find suitable crystal structures of unconstrained 16-membered lactone rings, instead of fully exploring the conformational space of this monomer, a computational investigation was carried out on a 15-membered ring thionolactone system which we named TTDL, adapting the starting geometry from that determined by X-ray diffraction for the related lactone N-(3-benzyl-2-oxo-1-oxacyclopentadecan-3-yl)benzamide. 32 The computational level (DFT approach with B3LYP and 6-31G(d,p) basis set) was selected on the basis of the recent comparative study by Guillaneuf et al, 5 showing the best match with the experimental activation energies for a similar radical ring opening reaction of CKAs. In the present study, however, the optimisations were also carried out in the presence of an empirical corrective term to account for dispersion forces (D3 method) 29 and attention will be focused on the Gibbs energy profile, rather than on the crude electronic energy.…”