Enantioselective Desymmetrization of Bisphenol Derivatives via Ir-Catalyzed Allylic Dearomatization

Abstract

Spirocyclic hexadienones with multiple stereogenic centers are frequently found in natural products but remain challenging targets to synthesize. Herein, we report the enantioselective desymmetrization of bisphenol derivatives via Ir-catalyzed allylic dearomatization reactions, affording spirocyclic hexadienone derivatives with up to three contiguous stereogenic centers in good yields (up to 90%) and excellent enantioselectivity (up to 99% ee). The high efficiency of this reaction is exemplified by the short reaction time (30 min), low catalyst loading (down to 0.2 mol %), and ability to perform the reaction on a gram-scale. The total syntheses of (+)-tatanan B and (+)-tatanan C were also realized using this Ir-catalyzed allylic dearomatization reaction as a key step.

Overcoming O–H Insertion to Para-Selective C–H Functionalization of Free Phenols: Rh(II)/Xantphos Catalyzed Geminal Difunctionalization of Diazo Compounds

“…Due to the importance of phenol motifs in natural products, pharmaceuticals, and functional materials, transformations of inexpensive and abundant phenols into their structurally more complex homologues have attracted much attention for a long time. , In particular, phenol derivatives that contain a diaryl all-carbon quaternary center α to the para -position have shown unique biological activities (Scheme a). − Therefore, the development of synthetic routes for para -selective C­(sp 2 )–H functionalization of phenols is highly attractive. − Although great advances have been made in the area of metal carbenoid induced C–H functionalization of (hetero)­arenes, − the direct C­(sp 2 )–H functionalization of free phenols in a chemo- and regioselective manner with diazo compounds is rather challenging and surprisingly rare, probably because the competitive O–H bond insertion is often found more favorable than C­(sp 2 )–H functionalization for carbenoids generated from a range of typical transition metals (e.g., Rh, Cu, Pd, Ag; Scheme b-i). − Very recently, remarkable advances have been achieved in highly para -selective C­(sp 2 )–H functionalization of free phenols with diazoesters, as reported independently by Zhang − and Shi, using the specific carbophilicity of gold catalysts, wherein the chemoselectivity is largely dependent on the nature of the supporting ligands (Scheme b-ii).…”

Enantioselective Synthesis of Medium-Sized-Ring Lactones via Iridium-Catalyzed Z-Retentive Asymmetric Allylic Substitution Reaction

“…Transition-metal (TM)-catalyzed asymmetric allylic substitution reactions have evolved as a powerful method for the construction of carbon–carbon and carbon–heteroatom bonds. − If a nucleophile and an allylic electrophile were placed in one molecule, an intramolecular cyclization might be achieved by TM-catalyzed allylic substitution reactions, leading to medium-sized-ring products with an olefin moiety embedded. However, an intrinsic challenge is encountered in this reaction design.…”

C–O Coupling/[4+2] Cycloaddition Tandem Reactions via Oxidative Dearomatization of BINOLs: Access to Bridged Polycyclic Compounds

“…Using cyclohexadienone as a key intermediate, a series of electrophilic substrates were employed to create C–C, C–O, C–S, C–N, and C–X (X = halogen) bonds bearing a quaternary carbon center in one step (Scheme a). Even when aromatic compounds or the attacking reagents were reasonably modified, subsequent tandem cyclization reactions could occur. Additionally, the dearomatized cycloaddition protocols were successfully performed to synthesize six-membered rings in a homodimeric or heterodimeric fashion to increase molecular complexity (Scheme b).…”