Markovnikov alcohols via epoxide hydroboration by molecular alkali metal catalysts

Summary Synthesis of branched “Markovnikov” alcohols is crucial to various chemical industries. The catalytic reduction of substituted epoxides under mild conditions is a highly attractive method for preparing such alcohols. Classical methods based on heterogeneous or homogeneous transition metal-catalyzed hydrogenation, hydroboration, or hydrosilylation usually suffer from poor selectivity, reverse regioselectivity, limited functional group compatibility, high cost, and/or low availability of the catalysts. Here we report the discovery of highly regioselective hydroboration of nonsymmetrical epoxides catalyzed by ligated archetypal reductants in organic chemistry ‒ alkali metal triethylborohydrides. The chemoselectivity and turnover efficiencies of the present catalytic approach are excellent. Thus, terminal and internal epoxides with ene, yne, aryl, and halo groups were selectively and quantitatively reduced under a substrate-to-catalyst ratio (S/C) of up to 1000. Mechanistic investigations point to a mechanism reminiscent of frustrated Lewis pair action on substrates in which a nucleophile and Lewis acid act cooperatively on the substrate. Graphical abstrac

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Investigation of a Heterobimetallic Effect in Reactions of Organometallics with Organic Radicals

Allylpalladium and allylnickel compounds containing group VI-group X metal-metal bonds were synthesized using the (2-(diphenylphosphino)ethyl)cyclopentadienyl (CpPPh) bridging ligand to kinetically stabilize these bonds. As with Pd(η3-allyl)Cl(PPh3), reaction of M’{M(η3-allyl)}(CO)3(μ-η5:η1-CpPPh) (M’ = Cr, Mo, or W; M = Ni or Pd) with phenyl and trityl radicals produced only 4,4,4-triphenyl-1-butene (trityl allyl), the trityl radical-allyl coupling product. However, the reaction appears to occur through a different mechanism. A possible heterobimetallic effect renders the conversions to trityl allyl different for each group VI metal

Reactivity of Cyclopentadienyl Molybdenum Compounds towards Formic Acid: Structural Characterization of CpMo(PMe₃)(CO)₂H, CpMo(PMe₃)₂(CO)H, [CpMo(μ-O)(μ‑O₂CH)]₂, and [Cp*Mo(μ-O)(μ‑O₂CH)]₂

The molecular structures of CpMo­(PMe₃)­(CO)₂H and CpMo­(PMe₃)₂(CO)H have been determined by X-ray diffraction, thereby revealing four-legged piano-stool structures in which the hydride ligand is <i>trans</i> to CO. However, in view of the different nature of the four basal ligands, the geometries of CpMo­(PMe₃)­(CO)₂H and CpMo­(PMe₃)₂(CO)H deviate from that of an idealized four-legged piano stool, such that the two ligands that are orthogonal to the <i>trans</i> H–Mo–CO moiety are displaced towards the hydride ligand. While Cp^RMo­(PMe₃)_3–<i>x</i>(CO)_<i>x</i>H (Cp^R = Cp, Cp*; <i>x</i> = 1, 2, 3) are catalysts for the release of H₂ from formic acid, the carbonyl derivatives, Cp^RMo­(CO)₃H, are also observed to form dinuclear formate compounds, namely, [Cp^RMo­(μ-O)­(μ-O₂CH)]₂. The nature of the Mo···Mo interactions in [CpMo­(μ-O)­(μ-O₂CH)]₂ and [Cp*Mo­(μ-O)­(μ-O₂CH)]₂ have been addressed computationally. In this regard, the two highest occupied molecular orbitals of [CpMo­(μ-O)­(μ-O₂CH)]₂ correspond to metal-based δ* (HOMO) and σ (HOMO–1) orbitals. The σ²δ*² configuration thus corresponds to a <i>formal</i> direct Mo–Mo bond order of zero. The preferential occupation of the δ* orbital rather than the δ orbital is a consequence of the interaction of the latter orbital with p orbitals of the bridging oxo ligands. In essence, lone-pair donation from oxygen increases the electron count so that the molybdenum centers can achieve an 18-electron configuration without the existence of a Mo–Mo bond, whereas a MoMo double bond is required in the absence of lone-pair donation

ProPhos: A Ligand for Promoting Nickel-Catalyzed Suzuki-Miyaura Coupling Inspired by Mechanistic Insights into Transmetalation

Nickel-catalyzed Suzuki–Miyaura coupling (Ni-SMC) offers the potential to reduce the cost of pharmaceutical process synthesis. However, its application has been restricted by challenges such as slow reaction rates, high catalyst loading, and a limited scope of heterocycles. Despite recent investigations, the mechanism of transmetalation in Ni-SMC, often viewed as the turnover-limiting step, remains insufficiently understood. We elucidate the “Ni-oxo” transmetalation pathway, applying PPh2Me as the ligand, and identify the formation of a nickel-oxo intermediate as the turnover-limiting step. Building on this insight, we develop a scaffolding ligand, ProPhos, featuring a pendant hydroxyl group connected to the phosphine via a linker. The design preorganizes both the nucleophile and the nickel catalyst, thereby facilitating transmetalation. This catalyst exhibits fast kinetics and robust activity across a wide range of heteroarenes, with a catalyst loading of 0.5–3 mol %. For arene substrates, the catalyst loading can be further reduced to 0.1 mol %

Assembly of a 3D Cobalt(II) Supramolecular Framework and Its Applications in Hydrofunctionalization of Ketones and Aldehydes

A ditopic nitrogen ligand (E)-N&prime;-(pyridin-4-ylmethylene)isonicotinohydrazide (L) containing both divergent pyridyl coordination sites and a hydrogen-bonding hydrazide&ndash;hydrazone moiety was synthesized. The Co(NCS)2-mediated self-assembly of L has resulted in the synthesis of a novel 3-dimensional (3D) supramolecular framework (1) that features both coordination and hydrogen bonding interactions. X-ray structural analysis reveals the formation and coordination mode of 1 in the solid state. The rational utilization of coordination bonds and hydrogen bonding interactions is confirmed and responsible for constructing the 3D materials. Catalytic studies using 1 in the presence of an activator are performed for the hydroboration and hydrosilylation reactions of ketones and aldehydes, and the results are compared with previously reported cobalt-based polymeric catalysts

Assembly of a 3D Cobalt(II) Supramolecular Framework and Its Applications in Hydrofunctionalization of Ketones and Aldehydes

A ditopic nitrogen ligand (E)-N′-(pyridin-4-ylmethylene)isonicotinohydrazide (L) containing both divergent pyridyl coordination sites and a hydrogen-bonding hydrazide–hydrazone moiety was synthesized. The Co(NCS)2-mediated self-assembly of L has resulted in the synthesis of a novel 3-dimensional (3D) supramolecular framework (1) that features both coordination and hydrogen bonding interactions. X-ray structural analysis reveals the formation and coordination mode of 1 in the solid state. The rational utilization of coordination bonds and hydrogen bonding interactions is confirmed and responsible for constructing the 3D materials. Catalytic studies using 1 in the presence of an activator are performed for the hydroboration and hydrosilylation reactions of ketones and aldehydes, and the results are compared with previously reported cobalt-based polymeric catalysts

Crystal structures of two formamidinium hexafluoridophosphate salts, one with batch-dependent disorder

Syntheses of the acyclic amidinium salts, morpholinoformamidinium hexafluoridophosphate [OC4H8N—CH=NH2]PF6 or C5H11N2O+·PF6−, 1, and pyrrolidinoformamidinium hexafluoridophosphate [C4H8N—CH= NH2]PF6 or C5H11N2+·PF6−, 2, were carried out by heating either morpholine or pyrrolidine with triethyl orthoformate and ammonium hexafluoridophosphate. Crystals of 1 obtained directly from the reaction mixture contain one cation and one anion in the asymmetric unit. The structure involves cations linked in chains parallel to the b axis by N—H...O hydrogen bonds in space group Pbca, with glide-related chains pointing in opposite directions. Crystals of 1 obtained by recrystallization from ethanol, however, showed a similar unit cell and the same basic structure, but unexpectedly, there was positional disorder [occupancy ratio 0.639 (4):0.361 (4)] in one of the cation chains, which lowered the crystal symmetry to the non-centrosymmetric space group Pca21, with two cations and anions in the asymmetric unit. In the pyrrolidino compound, 2, cations and anions are ordered and are stacked separately, with zigzag N—H...F hydrogen-bonding between stacks, forming ribbons parallel to (101), extended along the b-axis direction. Slight differences in the delocalized C=N distances between the two cations may reflect the inductive effect of the oxygen atom in the morpholino compound

Zerovalent Nickel Compounds Supported by 1,2-Bis(diphenylphosphino)benzene: Synthesis, Structures, and Catalytic Properties

Zerovalent nickel compounds which feature 1,2-bis­(diphenylphosphino)­benzene (dppbz) were obtained via the reactivity of dppbz towards Ni­(PMe₃)₄, which affords sequentially (dppbz)­Ni­(PMe₃)₂ and Ni­(dppbz)₂. Furthermore, the carbonyl derivatives (dppbz)­Ni­(PMe₃)­(CO) and (dppbz)­Ni­(CO)₂ may be obtained via the reaction of CO with (dppbz)­Ni­(PMe₃)₂. Other methods for the synthesis of these carbonyl compounds include (i) the formation of (dppbz)­Ni­(CO)₂ by the reaction of Ni­(PPh₃)₂(CO)₂ with dppbz and (ii) the formation of (dppbz)­Ni­(PMe₃)­(CO) by the reaction of (dppbz)­Ni­(CO)₂ with PMe₃. Comparison of the ν­(CO) IR spectroscopic data for (dppbz)­Ni­(CO)₂ with other (diphosphine)­Ni­(CO)₂ compounds provides a means to evaluate the electronic nature of dppbz. Specifically, comparison with (dppe)­Ni­(CO)₂ indicates that the <i>o</i>-phenylene linker creates a slightly less electron donating ligand than does an ethylene linker. The steric impact of the dppbz ligand in relation to other diphosphine ligands has also been evaluated in terms of its buried volume (%<i>V</i>_bur) and steric maps. The nickel center of (dppbz)­Ni­(PMe₃)₂ may be protonated by formic acid at room temperature to afford [(dppbz)­Ni­(PMe₃)₂H]⁺, but at elevated temperatures, effects catalytic release of H₂ from formic acid. Analogous studies with Ni­(dppbz)₂ and Ni­(PMe₃)₄ indicate that the ability to protonate the nickel centers in these compounds increases in the sequence Ni­(dppbz)₂ < (dppbz)­Ni­(PMe₃)₂ < Ni­(PMe₃)₄; correspondingly, the p<i>K</i>_a values of the protonated derivatives increase in the sequence [Ni­(dppbz)₂H]⁺ < [(dppbz)­Ni­(PMe₃)₂H]⁺ < [Ni­(PMe₃)₄H]⁺. (dppbz)­Ni­(PMe₃)₂ and Ni­(PMe₃)₄ also serve as catalysts for the formation of alkoxysilanes by (i) hydrosilylation of PhCHO by PhSiH₃ and Ph₂SiH₂ and (ii) dehydrocoupling of PhCH₂OH with PhSiH₃ and Ph₂SiH₂