Palladium-Catalyzed Intramolecular Diarylation of 1,3-Diketone in Total Synthesis of (±)-Spiroaxillarone A

Abstract

A sterically congested all-carbon quaternary center was installed for the first time via a Pd-catalyzed cascade diarylation with aryl bromides and acyclic 1,3-diketones. This method was used as a key step in the total synthesis of (±)-spiroaxillarone A. Computational experimental results indicated that the selective diarylation is accelerated by the higher free-energy barriers of the endothermic transmetalation and reductive elimination in the first arylation step.

Spirobisnaphthalenes from Fungi, Biological activities and Total Synthesis: A Research Review

“…In early 2022, with the developed methodology of Pd‐catalyzed intramolecular arylation for the construction of all‐carbon quaternary center, [57] the third strategy for the chemical synthesis of spiroaxillarone A was reported by Yang and co‐workers (Scheme 17). [58] In this strategy, the all‐carbon quaternary center was installed for the first time via a Pd‐catalyzed cascade diarylation with aryl bromides and acyclic 1,3‐diketones. First, the 1,3‐diketone 17 ‐ 3 was prepared through condensation of ketone 17 ‐ 1 and aldehyde 17 ‐ 2 , followed with Dess–Martin periodinane (DMP) oxidation.…”

“…Total Synthesis of Spiroaxillarone A in Yang's group. [58] oxidation. Then, under the Pd-catalyzed annulation conditions [Pd(OAc) 2 , 1,1'-bis(di-tert-butylphosphino)ferrocene (DTBPF), K 3 PO 4 ], 17-3 was converted to the key spiro skeleton compound 17-4, which was followed by the removal of the methyl groups with BBr 3 and the resultant phenols were reprotected by TIPDS to generate 17-5.…”

Total Synthesis and Biological Activity of (±)-Guignardin A, (±)-Palmarumycin B9, and Their Derivatives

“…Spirobisnaphthalene natural products, which were divided into five types based on the different linkages of the two naphthalenes, have a broad biological activities, such as antifungal, antimicrobial, antitumor, anticancer, antiparasitic, anti-inflammatory, and cytotoxic activity. − Many reports related to the total synthesis, structure revision, and modification, and biological activity evaluation of the spirobisnaphthalene natural products have appeared in recent years, − in which spiromamakone A and its monobenzo analogue (Figure B) showed excellent cytotoxicity against cervical carcinoma HeLa cells with IC 50 value of 0.77 and 0.56 μM, respectively. − Some of works have also been carried out in the total synthesis and biological activities of this family of natural products in our group. − …”

Pd-Catalyzed intermolecular asymmetric allylic dearomatization of 1-nitro-2-naphthols with MBH adducts

“…1 β-Naphthalenone is a core skeleton widely found in natural products and biologically active molecules. 2 Therefore, extensive efforts have been dedicated to the construction of β-naphthalenones through dearomatization of 2-naphthol derivatives. In this regard, asymmetric dearomatization of 1,3-disubstituted-2-naphthols has led to the formation of C–C, 3 C–N, 4 C–O 5 and other C–X (X = F, Cl, S) bonds with high efficiency in the past decade.…”