Total Synthesis of Amphidinolide E and Amphidinolide E Stereoisomers.

Four amphidinolide E stereoisomers, amphidinolide E (1), 2-epi-amphidinolide E (2), 19-epi-amphidinolide E (3), and 2-epi-19-epi-amphidinolide E (4), have been synthesized via the judicious union of aldehyde 5, allylsilanes 7 or 8, acids 9 or 10, and vinylstannane 6. The C19 stereocenters of the C19 epimeric allylsilanes 7 and 8 were introduced via crotylboration reactions early in the synthesis. [3+2]-Annulation reactions of aldehyde 5 with allylsilanes 7 and 8 were employed to set the core tetrahydrofuran units of 1-4. Finally, the C2 stereocenter was installed by esterification using acid 9, without incident, or with acid 10, in which case an unexpected and completely stereoselective inversion of C2 occurs.