Catalytic formation of cyclic-esters and -depsipeptides and chemical amplification by complexation with sodium ions

Lactide, LA, reacts in benzene solution at ∼70 °C with a polystyrene supported lithium alkoxide catalyst to release cycles (CHMeC(O)O)n to the solution by ring-opening polymerization and intra-chain trans-esterification. Polylactide, PLA, similarly reacts to yield cycles (CHMeC(O)O)n. The cycles back-react with the supported catalyst and with time form a dynamic combinatorial library of rings from which the 18-membered rings (CHMeC(O)O)6 are selectively removed by complexation with NaBPh4. In this way LA may be converted to (CHMeC(O)O)6 in ∼80% yield based on NaBPh4. Similar reactions occur for 3,6-substituted-1,4-dioxane-2,5-diones and 2,5-morpholine diones. These reactions occur with epimerization of the methine carbon stereocenter. In reactions involving 4 equiv. of LA or glycolide and NaBPh4, 4-dimethylaminopyridine in heated benzene the 18-membered cyclic esters form 1:1 adducts with NaBPh4. The structures of several of the isomers of (CHMeC(O)O)6 are reported together with complexes with NaBPh4. The NMR spectra for the two meso isomers and the six enantiomers are reported. Similar complexation of (CH2C(O)O)6, derived from glycolide, to Na+ is described along with its free unligated structure.

A new route to the formation of 18-membered rings derived from glycolide and lactide is described employing NaBPh4 which effectively removes these from a dynamic combinatorial library of rings.Figure optionsDownload as PowerPoint slide