A Short Synthesis of Delavatine A Unveils New Insights into Site-Selective Cross-Coupling of 3,5-Dibromo-2-pyrone

Abstract

The recognition of latent symmetry in delavatine A has enabled a short synthesis of the natural product starting from 3,5dibromo-2-pyrone. The concise synthetic route features a cascade process involving a 6π electrocyclization to construct the indane core of delavatine A. In addition, we have conducted detailed experimental and computational studies to gain an in-depth understanding of the mechanism of the observed site-selective cross-coupling of 3,5dibromo-2-pyrone. This insight may provide new avenues to achieve the selective cross-coupling of multiply halogenated heteroarenes.

A pyrone remodeling strategy to access diverse heterocycles: application to the synthesis of fascaplysin natural products

“…Interestingly, tetracyclic scaffolds such as lactam 8d and lactone 8e were accessed from indole-pyrones derived from tryptamine and tryptophol, respectively. Notably, 8d represents the core framework of tronocarpine (6). Next, we sought to investigate the tolerance of the overall transformation toward alterations of the electronics of the indole moiety.…”

“…4,5 In contrast, there have been limited examples within the second paradigm. While nucleophilic 1,6-ring opening of 2-pyrones has proven to be a particularly effective strategy for orchestrating novel cyclization events via reactive intermediate D 6 (our previous work 6a,b ), leveraging the dienolate functionality (E) accessible through 1,2-ring opening in annulation reactions remains underexplored. 7 We envisioned a strategy to N-fused bicycles in which a tethered reactive moiety (TRM) on 2-pyrone would engage an in situ generated dienolate (such as 1b) in an annulation reaction (Scheme 1b).…”

Capturing the Most Active State of a Palladium(0) Cross-Coupling Catalyst

“…These pre-equilibria strongly suppress the concentration of the active Pd(0) catalyst and throttle catalytic efficiency as a consequence and can even gate selective OA reactions. 19 Consider the classic cross-coupling catalyst (Ph3P)4Pd(0) as a representative case, which only reluctantly dissociates phosphine (Kd ≤ 1.5 × 10 -5 M) 12 to generate (Ph3P)2Pd(0). Assuming additional phosphine dissociation from the bis(phosphine) complex is at least as unfavorable as from the tris(phosphine) complex, the equilibrium concentration of monoligated Pd(0) generated from (Ph3P)4Pd(0) would be sub-nanomolar under normal circumstances and thus kinetically inconsequential (Fig 1B).…”

Recognition of Symmetry as a Powerful Tool in Natural Product Synthesis

“…22 In this context, Sarpong and coworkers designed a bioinspired total synthesis of delavatine A 27 based on trisaldehyde 28, which is proposed to be an intermediate in its biosynthesis. 23 22a The authors were able to further elaborate this route to also complete the formal synthesis of incarviatone A. 24 2.4 Oxycodone Scheme 7 Total synthesis of oxycodone (37) Oxycodone (37) is a semisynthetic morphinan alkaloid that is derived from the naturally occurring compound thebaine.…”