Improved synthetic route to enantiomerically pure samples of the tetrahydropyran-2-ylacetic acid core associated with the phytotoxic polyketide herboxidiene

The phosphine oxide (2), which embodies the tetrahydropyran-2-ylacetic acid core associated with the phytotoxic polyketide herboxidiene (1) and which is a key intermediate in a projected synthesis of this natural product, has been prepared in a highly enantio- and diastereo-selective manner. The piv otal steps in this new and improved synthesis of compound (2) involve Katsu ki-Sharpless asymmetric epoxidation of the allylic alcohol (4) to give epox ide (7) and subsequent ring-cleavage of the latter compound with trimethyla luminium to give diol (9). The derived acetate (10) is then readily ozonoly sed to give the previously reported aldehyde (11), although now in high ena ntiomeric excess. Compound (11) can be elaborated, by established chemistry , to the target oxide (2).