An efficient oxidative dearomatization–radical cyclization approach to symmetrically substituted bicyclic guttiferone natural products

Abstract

Detailed in this communication is an efficient synthetic approach towards the guttiferone family of natural products. Oxidatively unraveling a para-quinone monoketal followed by consecutive 5-exo radical cyclizations provides the bicyclic core. An additional strength of this approach is a late stage asymmetric desymmetrization of an advanced symmetric intermediate.

The Chemistry of the Polycyclic Polyprenylated Acylphloroglucinols

“…Based on this concept, the Njardarson research group designed and executed an elegant strategy that featured a late-stage desymmetrization reaction which could potentially provide entry to a large number of natural and designed PPAPs (Scheme 34). [98] As a demonstration, Scheme 32. Approaches to the synthesis of the PPAP core, according to Mehta et al [91,92,94] Scheme 33.…”

“…Synthesis of the PPAP core by a double radical cyclization/ desymmetrization strategy according to Njardarson and co-workers (2011). [98] Natural Product Synthesis Angewandte Chemie phenol derivative 309 was dearomatized under hypervalent iodine conditions in the presence of MeOH to afford cyclohexadienone 310 (75 % yield), which underwent tandem intramolecular radical cyclizations initiated by the two bromine substituents by using (TMS) 3 SiH and Et 3 B to afford the polycyclic intermediate 311 in 73 % yield. The two allyl side chains of 311 were converted into the corresponding prenyl groups by olefin cross-metathesis, and the so-obtained ketone 312 underwent successful desymmetrization through its lithium enolate followed by alkylation with methyl iodide to give a-methyl ketone 313 (73 % overall yield).…”

Recent Applications of the (TMS)3SiH Radical-Based Reagent

“…A nice example of two consecutive 5- exo cyclizations in a one-pot reaction is illustrated in Scheme 20 . Starting from dibromide 50 , the first cyclization via the radical 51 affords the desymmetrization of the molecule, whereas the second cyclization provides the bicyclic core 52 that is common of guttiferone family of natural products [ 53 ].…”

Synthetic efforts toward [3.3.1] bridged bicyclic phloroglucinol natural products

“…102 The Guttiferone family contains several members with such substitution patterns. Of those, guttiferone G ( 308 , Scheme 84) and guttiferone A ( 160 ) are currently the most biologically intriguing.…”