Homogeneous Gold-Catalyzed Oxidation Reactions.

Homogeneous gold catalysis has experienced extraordinary development since the dawn of this millennium. Oxidative gold catalysis is a vibrant and fertile subfield and has over the years delivered a diverse array of versatile synthetic methods of exceptional value to synthetic practices. This review aims to cover this topic in a comprehensive manner. The discussions are organized by the mechanistic aspects of the metal oxidation states and further by the types of oxidants or oxidizing functional groups. Synthetic applications of oxidative gold catalysis are also discussed.

Enantioselective Dearomative Cyclization Enabled by Asymmetric Cooperative Gold Catalysis.

A gold(I)-catalyzed enantioselective dearomatization is achieved via metal-chiral ligand cooperation. A new and divergent synthesis of chiral bifunctional binaphthyl-2-ylphosphines is developed to allow rapid access to these ligands, which in turn facilitate the application of this chemistry to a broad substrate scope including 1-naphthols, 2-naphthols, and phenols. Enantiomeric excesses up to 98 % are achieved via selective acceleration of one enantiomer formation enabled by hydrogen bonding between substrate and ligand remote basic group. DFT calculations lend support to the cooperative catalysis and substantiate the reaction stereochemical outcomes.

Chiral Bifunctional Phosphine Ligand-Enabled Cooperative Cu Catalysis: Formation of Chiral α,ß-Butenolides via Highly Enantioselective γ-Protonation.

α,ß-Butenolides with ≥96% enantiomeric excess are synthesized from ß,γ-butenolides via a novel Cu(I)-ligand cooperative catalysis. The reaction is enabled by a chiral biphenyl-2-ylphosphine ligand featuring a remote tertiary amino group. Density functional theory studies support the cooperation between the metal center and the ligand basic amino group during the initial soft deprotonation and the key asymmetric γ-protonation. Remarkably, other coinage metals, that is, Ag and Au, can readily assume the same role as Cu in this asymmetric isomerization chemistry.

Chiral Bifunctional Phosphine Ligand Enabling Gold-Catalyzed Asymmetric Isomerization of Alkyne to Allene and Asymmetric Synthesis of 2,5-Dihydrofuran.

The asymmetric isomerization of alkyne to allene is the most efficient and the completely atom-economic approach to this class of versatile axial chiral structure. However, the state-of-the-art is limited to tert-butyl alk-3-ynoate substrates that possess requisite acidic propargylic C-H bonds. Reported here is a strategy based on gold catalysis that is enabled by a designed chiral bifunctional biphenyl-2-ylphosphine ligand. It permits isomerization of alkynes with nonacidic α-C-H bonds and hence offers a much-needed general solution. With chiral propargylic alcohols as substrates, 2,5-disubstituted 2,5-dihydrofurans are formed in one step in typically good yields and with good to excellent diastereoselectivities. With achiral substrates, 2,5-dihydrofurans are formed with good to excellent enantiomeric excesses. A novel center-chirality approach is developed to achieve a stereocontrol effect similar to an axial chirality in the designed chiral ligand. The mechanistic studies established that the precatalyst axial epimers are all converted into the catalytically active cationic gold catalyst owing to the fluxional axis of the latter.

Total Synthesis and Structure Revision of Diplobifuranylone B.

An asymmetric total synthesis of diplobifuranylone B was achieved in 10 steps for the longest linear sequence and in 15.8% overall yield from commercially available methyl (R)-(+)-lactate and l-glutamic acid. This synthesis features a stereoselective construction of the key 2,5-dihydrofuran ring in the natural product via a recently developed asymmetric gold catalysis. The stereochemical flexibility offered by the catalysis enables an expedient revision of the reported structure of diplobifuranylone B, where the relative stereochemistry of the 2,5-dihydrofuran moiety was previously misassigned as cis instead of trans.

Wolff Rearrangement of Oxidatively Generated α-Oxo Gold Carbenes: An Effective Approach to Silylketenes.

Gold-catalyzed oxidations of alkynes by N-oxides offer direct access to reactive α-oxo gold carbene intermediates from benign and readily available alkynes instead of hazardous diazo carbonyl compounds. Despite various versatile synthetic methods developed based on this strategy, one of the hallmarks of α-oxo carbene/carbenoid chemistry, that is, the Wolff rearrangement, has not been realized in this context. This study discloses the first examples that show the Wolff rearrangement can be readily realized by α-oxo gold carbenes oxidatively generated from TBS-terminated alkynes (TBS=tert-butyldimethylsilyl). The thus-generated silylketenes can be either isolated pure or subsequently trapped by various internal or external nucleophiles in one pot to afford α-silylated carboxylic acids, their derivatives, or TBS-substituted allenes.

Bifunctional Ligand Enables Efficient Gold-Catalyzed Hydroalkenylation of Propargylic Alcohol.

Using the previously designed biphenyl-2-ylphosphine ligand, featuring a remote tertiary amino group, the first gold-catalyzed intermolecular hydroalkenylation of alkynes has been developed. Synthetically valuable conjugated dienyl alcohols are formed in moderate to good yields. A range of alkenyltrifluoroborates are allowed as the alkenyl donor, and no erosion of alkene geometry and/or the propargylic configuration are detected. DFT calculations confirm the critical role of the remote basic group in the ligand as a general-base catalyst for promoting this novel gold catalysis with good efficiency.

Highly Enantioselective Cobalt-Catalyzed Hydrosilylation of Alkenes.

A cobalt-catalyzed highly Markovnikov-type and enantioselective hydrosilylation of alkenes is developed for the efficient synthesis of valuable chiral dihydrosilanes. This protocol is operationally simple and atom-economy, and using relatively simple and readily available starting materials. The reaction is suitable for both aryl and aliphatic alkenes with excellent functional group tolerability. The reaction could be easily carried out in a gram-scale. The TOF and TON is up to 1800 and 860, respectively.

Prebiotic saccharides polymerization improves the encapsulation efficiency, stability, bioaccessibility and gut microbiota modulation of urolithin A liposomes.

This work was to investigate the effect of four prebiotic saccharides gum arabic (GA), fructooligosaccharide (FOS), konjac glucomannan (KGM), and inulin (INU) incorporation on the encapsulation efficiency (EE), physicochemical stability, and in vitro digestion of urolithin A-loaded liposomes (UroA-LPs). The regulation of liposomes on gut microbiota was also investigated by in vitro colonic fermentation. Results indicated that liposomes coated with GA showed the best EE, bioaccessibility, storage and thermal stability, the bioaccessibility was 1.67 times of that of UroA-LPs. The UroA-LPs coated with FOS showed the best freeze-thaw stability and transformation. Meanwhile, saccharides addition remarkably improved the relative abundance of Bacteroidota, reduced the abundances of Proteobacteria and Actinobacteria. The UroA-LPs coated with FOS, INU, and GA exhibited the highest beneficial bacteria abundance of Parabacteroides, Monoglobus, and Phascolarctobacterium, respectively. FOS could also decrease the abundance of harmful bacteria Collinsella and Enterococcus, and increase the levels of acetic acid, butyric acid and iso-butyric acid. Consequently, prebiotic saccharides can improve the EE, physicochemical stability, gut microbiota regulation of UroA-LPs, and promote the bioaccessibility of UroA, but the efficiency varied based on saccharides types, which can lay a foundation for the application of UroA in foods industry and for the enhancement of its bio-activities.

Chiral Bifunctional Phosphine Ligand Enables Gold-Catalyzed Asymmetric Isomerization and Cyclization of Propargyl Sulfonamide into Chiral 3-Pyrroline.

This work details an asymmetric gold-ligand cooperative catalysis that transforms readily accessible chiral/achiral propargylic sulfonamides into chiral 3-pyrrolines. A bifunctional biphenyl-2-ylphosphine ligand featuring a chiral tetrahydroisoquinoline fragment is essential for the observed metal-ligand cooperation and the asymmetric induction. 2,5-cis-3-Pyrrolines are formed with excellent diastereoselectivities in a "matched" scenario. The "mismatched" scenario by using the ligand enantiomer delivers 2,5-trans-3-pyrrolines with >5/1 diastereoselectivity. The synthetic utilities of this chemistry are demonstrated.

Gold-catalysed asymmetric net addition of unactivated propargylic C-H bonds to tethered aldehydes.

The asymmetric one-step net addition of unactivated propargylic C-H bond to aldehyde leads to an atom-economic construction of versatile chiral propargylic alcohols but has not been realized previously. Here we show its implementation in an intramolecular manner under mild reaction conditions. Via cooperative gold catalysis enabled by a chiral bifunctional phosphine ligand, this chemistry achieves asymmetric catalytic deprotonation of propargylic C-H (pKa > 30) by a tertiary amine group (pKa ~ 10) of the ligand in the presence of much more acidic aldehydic α-hydrogens (pKa ~ 17). The reaction exhibits a broad scope and readily accommodates various functional groups. The 5-/6-membered ring fused homopropargylic alcohol products are formed with excellent enantiomeric excesses and high trans-selectivities with or without a preexisting substrate chiral center. DFT studies of the reaction support the conceived reaction mechanism and the calculated energetics corroborate the observed stereoselectivity and confirm an additional metal-ligand cooperation.

A prediction of hematoma expansion in hemorrhagic patients using a novel dual-modal machine learning strategy.

Objective.Hematoma expansion is closely associated with adverse functional outcomes in patients with intracerebral hemorrhage (ICH). Prediction of hematoma expansion would therefore be of great clinical significance. We therefore attempted to predict hematoma expansion using a dual-modal machine learning (ML) strategy which combines information from non-contrast computed tomography (NCCT) images and multiple clinical variables.Approach.We retrospectively identified 140 ICH patients (57 with hematoma expansion) with 5616 NCCT images of hematoma (2635 with hematoma expansion) and 10 clinical variables. The dual-modal ML strategy consists of two steps. The first step is to derive a mono-modal predictor from a deep convolutional neural network using solely NCCT images. The second step is to achieve a dual-modal predictor by combining the mono-modal predictor with 10 clinical variables to predict hematoma growth using a multi-layer perception network.Main results. For the mono-modal predictor, the best performance was merely 69.5% in accuracy with solely the NCCT images, whereas the dual-modal predictor could boost the accuracy greatly to be 86.5% by combining clinical variables.Significance.To our knowledge, this is the best performance from using ML to predict hematoma expansion. It could be potentially useful as a screening tool for high-risk patients with ICH, though further clinical tests would be necessary to show its performance on a larger cohort of patients.

A Bifunctional Ligand Enables Gold-Catalyzed Hydroarylation of Terminal Alkynes under Soft Reaction Conditions.

An efficient gold-catalyzed hydroarylation of alkynes under soft reaction conditions is developed by utilizing a bifunctional ligand. This transformation features a broad substrate scope and thus exhibits moderate to excellent efficiency.