Concise asymmetric routes to 2,2,4-trisubstituted tetrahydrofurans via chiral titanium imide enolates: Key intermediates towards synthesis of highly active azole antifungals Sch 51048 and Sch 56592

Article abstract of DOI:10.1016/0040-4039(96)01203-8

Two complimentary approaches to the key (-)-(2R)-cis-tosylate 1 and its (+)-(2S)-enantiomer 15 via generation of chiral imide enolates having a 2,2-disubstituted olefin functionality in the β-position, are described. In a 'protecting group free' sequence, reaction of the titanium enolate generated from (4R)-benzyl-2-oxazolidinone derived imide 5b with s-trioxane provided a convenient intermediate 19 which could be directly subjected to 2,4-diastereoselective iodocyclization.