360-03-2Relevant articles and documents
Copper-catalyzed cascade radical cyclization of alkynoates: Construction of aryldifluoromethylated coumarins
Chen, Zhiwei,Huang, Xiaoxiao,Tang, Wei,Zeng, Piaopiao
supporting information, p. 10223 - 10227 (2021/12/10)
A mild and simple method is reported for the construction of 3-difluoroarylmethylated coumarins using α,α-difluoroarylacetic acids as an easily handled difluoromethyl source in reaction with ester 3-arylpropiolates under the promotion of copper. The reaction involves a proposed radical-triggered domino decarboxylative aryldifluoromethylation/5-exo cyclization/ester migration process that directly forms Csp2-CF2Ar and C-C bonds with good functional group tolerance. This journal is
Generation of Axially Chiral Fluoroallenes through a Copper-Catalyzed Enantioselective β-Fluoride Elimination
Liu, Peng,Mai, Binh Khanh,Nafie, Jordan,O'Connor, Thomas J.,Toste, F. Dean
, p. 13759 - 13768 (2021/09/07)
Herein we report the copper-catalyzed silylation of propargylic difluorides to generate axially chiral, tetrasubstituted monofluoroallenes in both good yields (27 examples >80%) and enantioselectivities (82-98% ee). Compared to previously reported synthetic routes to axially chiral allenes (ACAs) from prochiral substrates, a mechanistically distinct reaction has been developed: the enantiodiscrimination between enantiotopic fluorides to set an axial stereocenter. DFT calculations and vibrational circular dichroism (VCD) suggest that β-fluoride elimination from an alkenyl copper intermediate likely proceeds through a syn-β-fluoride elimination pathway rather than an anti-elimination pathway. The effects of the C1-symmetric Josiphos-derived ligand on reactivity and enantioselectivity were investigated. Not only does this report showcase that alkenyl copper species (like their alkyl counterparts) can undergo β-fluoride elimination, but this elimination can be achieved in an enantioselective fashion.
Optimization and sustainability assessment of a continuous flow Ru-catalyzed ester hydrogenation for an important precursor of a β2-adrenergic receptor agonist
García-Lacuna, Jorge,Hone, Christopher A.,Kappe, C. Oliver,Leslie, Kevin,Munday, Rachel,O'Kearney-McMullan, Anne,Prieschl, Michael
supporting information, p. 5762 - 5770 (2020/09/21)
The development of a ruthenium-catalyzed continuous flow ester hydrogenation using hydrogen (H2) gas is reported. The reaction was utilized for the reduction of an important precursor in the synthesis of abediterol, a β2-adrenoceptor agonist that has undergone phase IIa clinical trials for the treatment of asthma and chronic obstructive pulmonary disorder. The reaction was investigated within a batch autoclave by using a design of experiments (DoE) approach to identify important parameter effects. The optimized flow process was successfully operated over 6 h with inline benchtop19F NMR spectroscopy for reaction monitoring. The protocol is shown to be high yielding (98% yield, 3.7 g h?1) with very low catalyst loading (0.065 mol%). The environmental impact of the Ru-catalyzed hydrogenation was assessed and compared to an existing stoichiometric lithium aluminum hydride (LAH) reduction and sodium borohydride (NaBH4) reduction. The process mass intensity (PMI) for the Ru-catalyzed hydrogenation (14) compared favorably to a LAH reduction (52) and NaBH4reduction (133).
