We have previously shown that cyclic γ-silyloxy-β-hydroxy-α-diazoesters fragment when treated with Lewis acids to provide tethered aldehyde ynoates. These products can be used in intramolecular azomethine ylide 1,3-dipolar cycloadditions to give a polycyclic 2,5-dihydropyrrole, which is a common structural motif in natural products. Here we will report our efforts to apply this methodology to the synthesis of aspidospermine. In doing so, we are extending the reactivity to a one-pot fragmentation cycloaddition sequence via incorporating a suitable azomethine ylide precursor into the fragmentation starting material. To this end, we have prepared diazoester 4 as a fragmentation precursor. Upon treatment with 1 equivalent of indium triflate this compound productively fragmented, underwent Boc deprotection, and condensation to provide iminium salt 3 in good yield. The synthetic route to 3, use of 3 in an intramolecular 1,3-dipolar cycloaddition, and subsequent steps toward aspidospermine will be discussed.

Work toward the synthesis of aspidospermine via a ring fragmentation and 1,3-dipolarcycloaddition sequence

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.