skip to main content

Title: Probing Catalyst Speciation in Pd-MPAAM-Catalyzed Enantioselective C(sp 3 )–H Arylation: Catalyst Improvement via Destabilization of Off-Cycle Species
; ; ; ; ; ; ; ; ; ; ; ;
Award ID(s):
Publication Date:
Journal Name:
ACS Catalysis
Page Range or eLocation-ID:
11040 to 11048
Sponsoring Org:
National Science Foundation
More Like this
  1. The iron-catalyzed C(sp 2 )–C(sp 3 ) cross-coupling provides a highly economical route to exceedingly valuable alkylated arenes that are widespread in medicinal chemistry and materials science. Herein, we report an operationally-simple protocol for the selective C(sp 2 )–C(sp 3 ) iron-catalyzed cross-coupling of aryl chlorides with Grignard reagents at low catalyst loading. A broad range of electronically-varied aryl and heteroaryl chlorides underwent the cross-coupling using challenging alkyl organometallics possessing β-hydrogens with high efficiency up to 2000 TON. A notable feature of the protocol is the use of environmentally-friendly cyclic urea ligands. A series of guidelines to predict cross-coupling reactivity of aryl electrophiles is provided.
  2. A recent advance in the synthesis of alkenylated arenes was the demonstration that the Pd(OAc)2 catalyst precursor gives >95% selectivity toward styrene from ethylene and benzene under optimized conditions using excess Cu(II) carboxylate as the in situ oxidant [ Organometallics 2019, 38(19), 3532−3541]. To understand the mechanism underlying this catalysis, we applied density functional theory (DFT) calculations in combination with experimental studies. From DFT calculations, we determined the lowest-energy multimetallic Pd and Pd–Cu mixed metal species as possible catalyst precursors. From the various structures, we determined the cyclic heterotrinuclear complex PdCu2(μ-OAc)6 to be the global minimum in Gibbs free energy under conditions of excess Cu(II). For cyclic PdCu2(μ-OAc)6 and the parent [Pd(μ-OAc)2]3, we evaluated the barriers for benzene C–H activation through concerted metalation deprotonation (CMD). The PdCu2(μ-OAc)6 cyclic trimer leads to a CMD barrier of 33.5 kcal/mol, while the [Pd(μ-OAc)2]3 species leads to a larger CMD barrier at >35 kcal/mol. This decrease in the CMD barrier arises from the insertion of Cu(II) into the trimetallic species. Because cyclic PdCu2(μ-OAc)6 is likely the predominant species under experimental conditions (the Cu to Pd ratio is 480:1 at the start of catalysis) with a predicted CMD barrier within the range of the experimentallymore »determined activation barrier, we propose that cyclic PdCu2(μ-OAc)6 is the Pd species responsible for catalysis and report a full reaction mechanism based on DFT calculations. For catalytic conversion of benzene and ethylene to styrene at 120 °C using Pd(OAc)2 as the catalyst precursor and Cu(OPiv)2 (OPiv = pivalate) as the oxidant, an induction period of ∼1 h was observed, followed by catalysis with a turnover frequency of ∼2.3 × 10–3 s–1. In situ1H NMR spectroscopy experiments indicate that during the induction period, Pd(OAc)2 is likely converted to cyclic PdCu2(η2-C2H4)3(μ-OPiv)6, which is consistent with the calculations and consistent with the proposal that the active catalyst is the ethylene-coordinated heterotrinuclear complex cyclic PdCu2(η2-C2H4)3(μ-OPiv)6.« less