Enantioselective de novo synthesis of 14-hydroxy-6-oxomorphinans.

The enantioselective de novo synthesis of pharmacologically important 14-hydroxy-6-oxomorphinans is described. 4,5-Desoxynaltrexone and 4,5-desoxynaloxone were prepared using this route and their biological activities against the opioid receptors were measured.

Silver(I)-Catalyzed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres.

Bridged or caged polycyclic hydrocarbons have rigid structures that project substituents into precise regions of 3D space, making them attractive as linking groups in materials science and as building blocks for medicinal chemistry. The efficient synthesis of new or underexplored classes of such compounds is, therefore, an important objective. Herein, we describe the silver(I)-catalyzed rearrangement of 1,4-disubstituted cubanes to cuneanes, which are strained hydrocarbons that have not received much attention since they were first described in 1970. The synthesis of 2,6-disubstituted or 1,3-disubstituted cuneanes can be achieved with high regioselectivities, with the regioselectivity being dependent on the electronic character of the cubane substituents. A preliminary assessment of cuneanes as scaffolds for medicinal chemistry suggests cuneanes could serve as isosteric replacements of trans-1,4-disubstituted cyclohexanes and 1,3-disubstituted benzenes. An analogue of the anticancer drug sonidegib was synthesized, in which the 1,2,3-trisubstituted benzene was replaced with a 1,3-disubstituted cuneane.

Diphosphoryl-functionalized Polyoxometalates: Structurally and Electronically Tunable Hybrid Molecular Materials.

Herein, we report the synthesis and characterization of a new class of hybrid Wells-Dawson polyoxometalate (POM) containing a diphosphoryl group (P2 O6 X) of the general formula [P2 W17 O57 (P2 O6 X)]6- (X=O, NH, or CR1 R2 ). Modifying the bridging unit X was found to impact the redox potentials of the POM. The ease with which a range of α-functionalized diphosphonic acids (X=CR1 R2 ) can be prepared provides possibilities to access diverse functionalized hybrid POMs. Compared to existing phosphonate hybrid Wells-Dawson POMs, diphosphoryl-substituted POMs offer a wider tunable redox window and enhanced hydrolytic stability. This study provides a basis for the rational design and synthesis of next-generation hybrid Wells-Dawson POMs.

Electronic Structure and Photoactivity of Organoarsenic Hybrid Polyoxometalates.

Organofunctionalization of polyoxometalates (POMs) allows the preparation of hybrid molecular systems with tunable electronic properties. Currently, there are only a handful of approaches that allow for the fine-tuning of POM frontier molecular orbitals in a predictable manner. Herein, we demonstrate a new functionalization method for the Wells-Dawson polyoxotungstate [P2W18O62]6- using arylarsonic acids which enables modulation of the redox and photochemical properties. Arylarsonic groups facilitate orbital mixing between the organic and inorganic moieties, and the nature of the organic substituents significantly impacts the redox potentials of the POM core. The photochemical response of the hybrid POMs correlates with their computed and experimentally estimated lowest unoccupied molecular orbital energies, and the arylarsonic hybrids are found to exhibit increased visible light photosensitivity comparable with that of arylphosphonic analogues. Arylarsonic hybridization offers a route to stable and tunable organic-inorganic hybrid systems for a range of redox and photochemical applications.

Synthesis of New Morphinan Opioids by TBADT-Catalyzed Photochemical Functionalization at the Carbon Skeleton.

The synthesis of new morphinan opioids by the addition of photochemically generated carbon-centered radicals to substrates containing an enone in the morphinan C-ring, is described. Using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom transfer photocatalyst, diverse radical donors can be used to prepare a variety of C8-functionalized morphinan opioids. This work demonstrates the late-stage modification of complex, highly functionalized substrates.

Gold(I)-Catalyzed Nucleophilic Allylation of Azinium Ions with Allylboronates.

Gold(I)-catalyzed nucleophilic allylations of pyridinium and quinolinium ions with various allyl pinacolboronates are reported. The reactions are completely selective with respect to the site of the azinium ion that is attacked, to give various functionalized 1,4-dihydropyridines and 1,4-dihydroquinolines. Evidence suggests that the reactions proceed through nucleophilic allylgold(I) intermediates formed by transmetalation from allylboronates. Density functional theory (DFT) calculations provided mechanistic insight.

Nickel-Catalyzed Arylative Cyclizations of Alkyne- and Allene-Tethered Electrophiles using Arylboron Reagents.

The use of arylboron reagents in metal-catalyzed domino addition-cyclization reactions is a well-established strategy for the preparation of diverse, highly functionalized carbo- and heterocyclic products. Although rhodium- and palladium-based catalysts have been commonly used for these reactions, more recent work has demonstrated nickel catalysis is also highly effective, in many cases offering unique reactivity and access to products that might otherwise not be readily available. This review gives an overview of nickel-catalyzed arylative cyclizations of alkyne- and allene-tethered electrophiles using arylboron reagents. The scope of the reactions is discussed in detail, and general mechanistic concepts underpinning the processes are described.

Enantioselective nickel-catalyzed anti-arylmetallative cyclizations onto acyclic electron-deficient alkenes.

Enantioselective nickel-catalyzed reactions of (hetero)arylboronic acids or alkenylboronic acids with substrates containing an alkyne tethered to various acyclic electron-deficient alkenes are described.

Enantioselective Nickel-Catalyzed anti-Arylmetallative Cyclizations onto Acyclic Ketones.

Domino reactions involving nickel-catalyzed additions of (hetero)arylboronic acids to alkynes, followed by cyclization of the alkenylnickel intermediates onto tethered acyclic ketones to give chiral tertiary-alcohol-containing products in high enantioselectivities, are described. The reversible E/Z isomerization of the alkenylnickel intermediates enables overall anti-arylmetallative cyclization to occur. The ring system of the products are substructures of certain diarylindolizidine alkaloids.

Bundled interventions for consumption management and monitoring of personal protective equipment in COVID-19 pandemic in Hong Kong local hospitals.

Since the outbreak of COVID-19 in December 2019, there had been global shortage of personal protective equipment (PPE) supply due to the breakage of supply chain and also the forbidding of PPE exported by various countries. This situation had greatly affected the healthcare services in local hospitals of Hong Kong. To maintain the availability of PPE for healthcare workers in high-risk clinical settings, the cluster management of New Territories West Cluster, Hospital Authority, had implemented a bundle of interventions in controlling and managing the PPE consumption and ensuring its proper use. A Taskforce on Management of PPE was set up in February 2020 with the aim to monitor and manage the use of PPE in five local hospitals and eight general outpatient clinics of New Territories West Cluster, which were governed in a cluster basis, under the COVID-19 epidemic. Interventions including cutting down non-essential services, implementing telecare, monitoring PPE consumption at unit level and PPE stock at the Cluster Central Distribution Centre and forming mobile infection teams were implemented. The updated PPE standards and usage guidelines to clinical staff were promulgated through forums, newsletters and unit visits. The PPE consumption rates of individual unit were reviewed. Significant decrease in PPE consumption rates was noted when comparing with the baseline data. Comparing the data between 20 February and 1 June 2020, the overall PPE consumption rates were reduced by 64% (r=-0.841; p<0.001) while the PPE consumption rates in anaesthesia and operating theatres, and isolation and surveillance wards were reduced by 47% (r=-0.506; p=0.023) and 49% (r=-0.810; p<0.001), respectively. A bundled approach, including both administrative measures and staff education, is effective in managing PPE consumption during major infection outbreaks especially when PPE supply is at risk.

Catalytic enantioselective arylative cyclizations of alkynyl 1,3-diketones by 1,4-rhodium(i) migration.

The enantioselective synthesis of densely functionalized polycarbocycles by the rhodium(i)-catalyzed reaction of arylboronic acids with 1,3-diketones is described. The key step in these desymmetrizing domino addition-cyclization reactions is an alkenyl-to-aryl 1,4-Rh(i) migration, which enables arylboronic acids to function effectively as 1,2-dimetalloarene surrogates.

Enantioselective nickel-catalyzed arylative and alkenylative intramolecular 1,2-allylations of tethered allene-ketones.

The enantioselective nickel-catalyzed reaction of tethered allene-ketones with (hetero)arylboronic acids or potassium vinyltrifluoroborate is described. Carbonickelation of the allene gives allylnickel species, which undergo cyclization by 1,2-allylation to produce chiral tertiary-alcohol-containing aza- and carbocycles in high diastereo- and enantioselectivities.

Rhodium-catalyzed arylative cyclization of alkynyl malonates by 1,4-rhodium(i) migration.

The synthesis of functionalized 1-tetralones by the rhodium(i)-catalyzed reaction of alkynyl malonates with arylboronic acids is described. These arylative cyclizations proceed via an alkenyl-to-aryl 1,4-Rh(i) migration as a key step. Preliminary results of an enantioselective variant of these reactions are also presented.

Iridium-catalyzed 1,5-(aryl)aminomethylation of 1,3-enynes by alkenyl-to-allyl 1,4-iridium(i) migration.

A novel multicomponent coupling reaction involving the iridium-catalyzed 1,5-difunctionalization of 1,3-enynes with arylboronic acids and triazinanes is described. A key step in this 1,5-(aryl)aminomethylation reaction is the alkenyl-to-allyl 1,4-iridium(i) migration.

Nickel-catalyzed, ligand-free, diastereoselective synthesis of 3-methyleneindan-1-ols.

Nickel-catalyzed, highly diastereoselective annulations between activated allenes and 2-acetylarylboronic acid or 2-formylarylboronic acids are reported. No ligand for nickel is required, and the reactions proceed efficiently at room temperature to give a broad range of substituted 3-methyleneindan-1-ols. Preliminary results of an enantioselective variant are also described.

Synthesis of multisubstituted pyrroles by nickel-catalyzed arylative cyclizations of N-tosyl alkynamides.

The synthesis of multisubstituted pyrroles by the nickel-catalyzed reaction of N-tosyl alkynamides with arylboronic acids is reported. These reactions are triggered by alkyne arylnickelation, followed by cyclization of the resulting alkenylnickel species onto the amide. The reversible E/Z isomerization of the alkenylnickel species is critical for cyclization. This method was applied to the synthesis of pyrroles that are precursors to BODIPY derivatives and a biologically active compound.

Remote Nucleophilic Allylation by Allylrhodium Chain Walking.

Metal migration through a carbon chain is a versatile method for achieving remote functionalization. However, almost all known examples involve the overall net migration of alkylmetal species. Here, we report that allylrhodium species obtained from hydrorhodation of 1,3-dienes undergo chain walking toward esters, amides, or (hetero)arenes over distances of up to eight methylene units. The final, more highly conjugated allylrhodium species undergo nucleophilic allylation with aldehydes and with an imine to give Z-homoallylic alcohols and amines, respectively.