Isothiourea-catalysed enantioselective radical conjugate addition under batch and flow conditions

Financial support was provided by the Spanish Government (RTI2018-095038-B-I00), “Comunidad de Madrid” for European Structural Funds (S2018/NMT-4367) and proyectos sinergicos I+D (Y2020/NMT-6469). J. A. F.-S. thanks the Spanish Government for a Ramón y Cajal contract. The research leading to these results has received funding from the EaSI-CAT centre for Doctoral Training (M.T.W) and Carlsberg Foundation (M.J.).The photocatalytic generation of α-amino radicals is combined with chiral isothiourea derived α,β-unsaturated acyl ammonium intermediates. The reaction proceeds via a [3+2] radical-polar crossover mechanism to generate γ-lactams in good yields and enantioselectivities. The enantioselective radical conjugate addition was carried out under batch and flow conditions.Publisher PDFPeer reviewe

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies

Fluorinated Sulfinates as Source of Alkyl Radicals in the Photo-Enantiocontrolled β-Functionalization of Enals

The generation of sulfonyl radicals has long been known as a flexible strategy in a wide range of different sulfonylative transformations. Meanwhile their use in alkylation processes has been somehow limited due to their inherent difficulty in evolving to less-stable radicals after sulfur dioxide extrusion. Herein we report a convenient strategy that involves gem-difluorinated sulfinates as an “upgrading-mask”, allowing these precursors to decompose into their corresponding alkyl radicals. The electron–donor character of sulfinates in the formation of an electron donor–acceptor (EDA) complex with transient iminium ions is displayed, achieving the first example of a stereocontrolled light-driven insertion of gem-difluoro derivatives into unsaturated aldehydes. This methodology is compatible with flow conditions, maintaining identical levels of enantiocontrolFinancial support was provided by the European Research Council (ERC-CoG, contract number: 647550), Spanish Government (RTI2018-095038-B-I00), “Comunidad de Madrid” and European Structural Funds (S2018/NMT-4367

Macrocyclic Hosts in Asymmetric Phase-Transfer Catalyzed Reactions

The introduction and development of neutral macrocyclic hosts capable of complexing ions within their pre-organized cavity, has been of utmost importance in supramolecular chemistry. Their ability to form stable organic-soluble metal-macrocycle complexes opened up the way to their application in phase-transfer catalysis (PTC) as a viable alternative to quaternary onium salts. In particular, their conformationally rigid preorganized backbone, accommodating organic substrates in defined orientations, promotes highly efficient stereoselective reactions. This short review summarizes the applications of neutral macrocyclic hosts in stereoselective PTC, highlighting the difference and possible complementarity with quaternary ammonium salts

Asymmetric Synthesis of α-Trifluoromethylthio-β-Amino Acids under Phase Transfer Catalysis

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: https://pubs.acs.org/doi/abs/10.1021/acs.orglett.9b04195The first asymmetric α-trifluoromethylthiolation of 2-substituted isoxazolidin-5-ones was developed using Maruoka type N-spiro ammonium catalysts under phase-transfer conditions. The resulting products, containing a trifluoromethylthiolated quaternary chiral carbon, were obtained in moderate to good yields and up to 98:2 enantiomeric ratio. Moreover, the easy N-O bond cleavage provided access to undescribed α-trifluoromethylthio-β2,2-amino acids, with promising applications in biochemistry and medicinal chemistry.We are grateful to the Spanish Government (CTQ2015-64561-R and RTI2018-095038-B-I00), “Comunidad de Madrid” and European Structural Funds (S2018/NMT-4367). R.I.R thanks Fundación Carolina for a graduate fellowship. G.D.S and M.S. thank the University of Salerno for financial support (FARB

Asymmetric trifluoromethylthiolation of azlactones under chiral phase transfer catalysis

The first enantioselective method for the installation of the SCF3 group at the C-4 position of azlactones is described in the present communication under quinidinium phase transfer catalysis. The higher performance of substrates containing electron-rich 2-aryl groups at the azlactone was rationalized using DFT calculationsWe are grateful to the Spanish Government (RTI2018-095038-B-I00, CTQ, CTQ2016-76061-P), “Comunidad de Madrid” and European Structural Funds (S2018/NMT-4367