The enantioselective hydrogenation of cyclic enamides has been achieved using an earth‐abundant cobalt‐bisphosphine catalyst. Using CoCl2/(S,S)‐Ph‐BPE, several trisubstituted carbocyclic enamides were reduced with high activity and excellent enantioselectivity (up to 99 %) to the corresponding saturated amides. The methodology can be extended to the synthesis of chiral amines by base hydrolysis of the hydrogenation products. Preliminary mechanistic investigations reveal the presence of a high spin cobalt (II) species in the catalytic cycle. We propose that the hydrogenation of the carbon‐carbon double bond proceeds via a sigma‐bond‐metathesis pathway.
Purpose: To establish the extent of agreement for ISCEV standard reference pattern reversal VEPs (prVEPs) acquired at three European centres, to determine any effect of sex, and to establish reference intervals from birth to adolescence. Methods: PrVEPs were recorded from healthy reference infants and children, aged 2 weeks to 16 years, from three centres using closely matched but non-identical protocols. Amplitudes and peak times were modelled with orthogonal quadratic and sigmoidal curves, respectively, and two-sided limits, 2.5th and 97.5th centiles, estimated using nonlinear quantile Bayesian regression. Data were compared by centre and by sex using median quantile confidence intervals. The ‘critical age’, i.e. age at which P100 peak time ceased to shorten, was calculated. Results: Data from the three centres were adequately comparable. Sex differences were not clinically meaningful. The pooled data showed rapid drops in P100 peak time which stabilised by 27 and by 34 weeks for large and small check widths, respectively. Post-critical-age reference limits were 87–115 ms and 96–131 ms for large and small check widths, respectively. Amplitudes varied markedly and reference limits for all ages were 5–57 μV and 3.5–56 μV for large and small check widths, respectively. Conclusions: PrVEP reference data could be combined despite some methodology differences within the tolerances of the ISCEV VEP Standard, supporting the clinical benefit of ISCEV Standards. Comparison with historical data is hampered by lack of minimum reporting guidelines. The reference data presented here could be validated or transformed for use elsewhere.
Direct asymmetric reductive amination of bio‐based levulinic acid (LA) to the enantioenriched 5‐methylpyrrolidinone is achieved by using a readily available chiral Ru/bisphosphine catalyst with excellent enantioselectivity (up to 96 % ee) and high isolated yield (up to 89 %). Methyl levulinate (ML), a byproduct from the industrial production of 2,5‐furandicarboxylic acid (FDCA), can be used instead of LA with similar reactivity and selectivity. Mass spectrometry and isotope labelling studies indicate that the chiral lactam is formed via imine‐enamine tautomerization/cyclization followed by asymmetric hydrogenation of the cyclic enamide.
Biomass derived glycolaldehyde was employed as C1 building block for the N‐formylation of secondary amines using air as oxidant. The reaction is atom economic, highly selective and proceeds under catalyst free conditions. This strategy can be used for the synthesis of cyclic and acyclic formylamines, including DMF. Mechanistic studies suggest a radical oxidation pathway.
Die enantioselektive Hydrierung von cyclischen Enamiden wurde mit einem Cobalt‐Bisphosphin‐Katalysator erreicht. Die Reduktion verschiedenster dreifach substituierter carbocyclischen Enamide zu den entsprechenden gesättigten Amiden erfolgte mit hoher Aktivität und ausgezeichneter Enantioselektivität (bis zu 99 %) unter Verwendung des Systems CoCl2/(S,S)‐Ph‐BPE. Die Methode lässt sich auf die Synthese chiraler Amine durch eine basische Hydrolyse der Hydrierungsprodukte ausweiten. Erste mechanistische Untersuchungen deuten auf die Anwesenheit einer high‐spin Cobalt(II)‐Spezie im katalytischen Cyclus hin. Wir postulieren die Hydrierung der Kohlenstoff‐Kohlenstoff‐Doppelbindung über einen Sigma‐Bindungs‐Metathese‐Weg.