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Org. Process Res. Dev. 2023, 27, 198.
DOI: 10.1021/acs.oprd.2c00332 ◆ During the commercial process development,
several operational requirements were identified as keys to ensure a successful
process: (1) the Pd catalyst must be charged to the reaction mixture at the
reaction temperature; (2) slow addition of boroxine 2 was required to ensure
complete conversion of the aryl chloride; (3) in the event of incomplete aryl
chloride consumption, additional catalyst was required along with a boroxine
charge to ensure complete conversion. ◆ Kinetic and mechanistic studies revealed
that the use of KOAc as the base resulted in ligand activation from DPEphos
(L1) to DPEphos monoxide (L2) to produce the active catalytic species. ◆ Transmetalation from pretransmetalation
complex 9 is the rate-determining step (RDS) in KOAc process. Simple alteration
of the base to K2CO3 shifted the RDS to the formation of pre-transmetalation
complex 9 ◆ Importantly, switching the base from KOAc
to K2CO3 i
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