A facilitated cyclic ether formation and its potential application in solid-phase peptide and organic synthesis

A "trimethyl lock" system has been known to facilitate lactonization reacti ons through that has been termed a stereopopulation control mechanism. We h ave found that a similar trimethyl lock system can also facilitate cyclic e ther formation with the concomitant release of a carboxylic acid in the pre sence of anhydrous tetrabutylammonium fluoride, To study this base-mediated trimethyl lock-facilitated cyclic ether formation, we synthesized fifteen model compounds. All model compounds underwent base-mediated cyclic ether f ormation in high yields at 0 degrees C to room temperature (r.t.) with the concomitant release of the attached carboxylate. Such a system potentially could be used for the development of a two-dimensional linker for solid pha se peptide and organic synthesis.