25240-59-9Relevant articles and documents
Hydrogen Evolution from Telescoped Miyaura Borylation and Suzuki Couplings Utilizing Diboron Reagents: Process Safety and Hazard Considerations
Borkar, Indrakant,Brewer, Alison Campbell,Buser, Jonas Y.,Campos, Odilon,Fleming, Jeffrey,Forst, Mindy B.,Hansen, Caoimhe,Humenik, Ashley,Jeffery, Stephen,Kokitkar, Prashant B.,Kolis, Stanley P.,Lambertus, Gordon R.,Martinelli, Joseph R.,McCartan, Ciaran,Merritt, Jeremy M.,Moursy, Hossam,Murphy, Donal,Murray, Michael M.,O'Donnell, Kevin,O'Sullivan, Rita,Richardson, Gary A.,Xia, Han
, (2021/08/30)
The hazard assessment of a telescoped Miyaura borylation and Suzuki coupling reaction employing bis(pinacolato)diboron (BisPin), used in the developmental synthesis of an intermediate for abemaciclib, led to the observation of hydrogen being generated. Quantitative headspace GC and solution 11B NMR were used to show that the rapid decomposition of the excess BisPin from the borylation under the aqueous basic conditions of the Suzuki reaction was responsible for H2 generation. The moles of H2 observed were found equal to the BisPin excess, which is rationalized by mass balance and a stoichiometric reaction. The possible generation of the stoichiometric levels of H2 should be considered in hazard assessments of this class of reaction. Kinetic and process modeling was used to minimize the risk upon scale-up, and results for commercial manufacturing batches are presented, which showed good agreement with the lab scale data. Furthermore, the hydrogen evolution potentials of other common borylating agents including bisboronic acid (BBA) and pinacol borane were demonstrated.
Ruthenium-catalyzed reduction of carbon dioxide to formaldehyde
Bontemps, Sébastien,Vendier, Laure,Sabo-Etienne, Sylviane
supporting information, p. 4419 - 4425 (2014/04/03)
Functionalization of CO2 is a challenging goal and precedents exist for the generation of HCOOH, CO, CH3OH, and CH4 in mild conditions. In this series, CH2O, a very reactive molecule, remains an elementary C1 building block to be observed. Herein we report the direct observation of free formaldehyde from the borane reduction of CO2 catalyzed by a polyhydride ruthenium complex. Guided by mechanistic studies, we disclose the selective trapping of formaldehyde by in situ condensation with a primary amine into the corresponding imine in very mild conditions. Subsequent hydrolysis into amine and a formalin solution demonstrates for the first time that CO2 can be used as a C 1 feedstock to produce formaldehyde.
Substituent effects on oxidation-induced formation of quinone methides from arylboronic ester precursors
Cao, Sheng,Christiansen, Robin,Peng, Xiaohua
, p. 9050 - 9058 (2013/07/26)
A series of arylboronic esters containing different aromatic substituents and various benzylic leaving groups (Br or N+Me3Br -) have been synthesized. The substituent effects on their reactivity with H2O2 and formation of quinone methide (QM) have been investigated. NMR spectroscopy and ethyl vinyl ether (EVE) trapping experiments were used to determine the reaction mechanism and QM formation, respectively. QMs were not generated during oxidative cleavage of the boronic esters but by subsequent transformation of the phenol products under physiological conditions. The oxidative deboronation is facilitated by electron-withdrawing substituents, such as aromatic F, NO2, or benzylic N+Me 3Br-, whereas electron-donating substituents or a better leaving group favor QM generation. Compounds containing an aromatic CH 3 or OMe group, or a good leaving group (Br), efficiently generate QMs under physiological conditions. Finally, a quantitative relationship between the structure and activity has been established for the arylboronic esters by using a Hammett plot. The reactivity of the arylboronic acids/esters and the inhibition or facilitation of QM formation can now be predictably adjusted. This adjustment is important as some applications may benefit and others may be limited by QM generation. Tunable quinone methide formation: Aromatic substituents and the benzylic leaving group strongly affect the H 2O2-induced formation of quinone methides (QMs) from arylboronic esters (see scheme). The reactivity of arylboronic esters can be predictably adjusted by varying substituents. Copyright
