Highly Substituted Oxabicyclic Derivatives from Furan: Synthesis of (±)-Platensimycin

Abstract

A stereocontrolled approach to a key platensimycin intermediate was achieved from a commercially available furylcarboxylate. Key to our approach is the highly efficient formal [4 + 3] cyclocondensation of a substituted furan with tetrabromocyclopropene along with an intramolecular γ-alkylation to construct the final ring of the caged intermediate.

The Tandem Ring Opening/Ring Closing Metathesis Route to Oxaspirocycles: An Approach to Phelligridin G

“…In our desire to expand this utility of this methodology, we looked at the highly reactive perhalogenated cyclopropenes as cycloaddition partners ( Scheme 4 ). With the assistance of these compounds, we have been able to develop building blocks leading to the synthesis of several natural products [ 20 , 21 ]. It was felt that the cycloaddition of perhalocyclopropenes would be more efficient as the initial cycloadduct spontaneously rearranges to the ring-expanded system thus preventing the retro-Diels-Alder reaction from taking place.…”

Strained Alkenes in Natural Product Synthesis

“…Oblak and Wright envisioned the utilization of a unique intermolecular Diels-Alder cycloaddition of two readily accessible precursors, tetrabromocyclopropene 9 and furan 8, to quickly assemble the carbon framework 14 of platensimycin (Scheme 2). [19] Toward this end, gently heating tetrabromocyclopropene 9 with furan 8 initiated a near instantaneous exo-selective [4+2] cycloaddition, followed by in situ rearrangement to afford an inconsequential mixture of tetrabromides 10 and 11. The endo/exo selectivity obtained in these perhalocyclopropene cycloadditions has remained unclear since they were first reported by Tobey and Law in 1968.…”

“…Formal synthesis of platensimycin described by Oblak and Wright in 2011. [19] TBS = tert-butyldimethylsilyl, Tf = trifluoromethanesulfonyl. Scheme 3.…”

Platensimycin and its relatives: A recent story in the struggle to develop new naturally derived antibiotics

“…In another stereocontrolled approach, the key intermediate (386) of platensimycin was synthesized using commercially available furylcarboxylate (387). 128 The retrosynthetic route to the cage-like structure is shown in Scheme 77.…”