Enantioselective palladium-catalysed conjugate addition of arylsiloxanes

Gini, Francesca; Hessen, Bart; Feringa, Ben L.; Minnaard, Adriaan J.

doi:10.1039/b616969d

Cited by 49 publications

(18 citation statements)

References 31 publications

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“…153 With a very simple Pd(TFA) 2 /Me-DuPhos catalyst in aqueous THF, Minnard and co-workers showed that a variety of aryl boronic acids and α,β-unsaturated ketones were coupled with good yields and excellent enantioselectivity (Scheme 93). Aldehydes and esters were less successful coupling partners.…”

Section: Enantioselective Reactions Involving Carbopalladationmentioning

confidence: 99%

Palladium(II)-Catalyzed Alkene Functionalization via Nucleopalladation: Stereochemical Pathways and Enantioselective Catalytic Applications

2011

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Section: Enantioselective Reactions Involving Carbopalladationmentioning

confidence: 99%

Palladium(II)-Catalyzed Alkene Functionalization via Nucleopalladation: Stereochemical Pathways and Enantioselective Catalytic Applications

2011

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“…Conversely, the utilization of highly reactive organometallic reagents to obtain related products has been studied extensively . Although numerous advances have been made in Pd‐catalyzed conjugate addition with organometallic reagents (Grignards, organozincs, and boronic acids) in the past decade, the direct Pd‐catalyzed reductive Heck reaction of alkenes with aryl halides has hardly been investigated . In general, the replacement of expensive air‐ and moisture‐ sensitive organometallic reagents with aryl halides is very tempting for industrial synthetic transformations.…”

Section: Introductionmentioning

confidence: 99%

Importance of the Reducing Agent in Direct Reductive Heck Reactions

et al. 2017

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The role of the reductant in the palladium N‐heterocyclic carbene (NHC) catalyzed reductive Heck reaction and its effect on the mechanism of the reaction is reported. For the first time in this type of transformation, the palladium‐NHC‐catalyzed reductive Heck reaction was shown to proceed in the presence of LiOMe and iPrOH even at 10 °C to give the products very efficiently in excellent yields and with exceptional chemoselectivities. This study shows that the reaction proceeds through two distinct mechanisms that depend on the nature of the reducing agent. In the presence of a protic solvent or acidic medium the reaction undergoes protonation to yield the reduced product, whereas in the absence of proton source, it proceeds through the insertion of the reductant followed by reductive elimination. The kinetic data reveal that the oxidative addition is the rate‐determining step in the reaction. The reaction profiles show first‐order kinetics in aryl iodide and Pd and zero‐order kinetics in LiOMe, benzylideneacetone, and the excess amount of NHC ligand. In addition, the reaction progress kinetic analysis shows that neither catalyst decomposition nor product inhibition occurs during the reaction. DFT calculations of the key steps confirm that the oxidative addition step is the rate‐determining step in the reaction. Deuterium‐labeling experiments indicate that the product is formed by the protonation of the Pd−Calkyl bond of the intermediate formed after enone insertion into the Pd−CAr bond. Application of chiral NHC ligands in the asymmetric reductive Heck reaction only results in poor enantioselectivities (enantiomeric excess up to 20 %) and is also substrate specific. DFT calculations suggest that the migration of the aryl group to the alkene of the substrate is the enantioselectivity‐determining step of the reaction. It is further shown that if the steric bulk at the enone is small (a methyl group), the two transition state barriers from [PdII(L2)(ArI)(enone)] species Cre and Csi, which have the re and si face of the enone substrate coordinated to Pd, are very similar, in line with the experimental results. With a slightly larger group (an isopropyl substituent) a significant difference in energy barriers is calculated (2.6 kcal mol−1), and in the experiment this product is formed with a modest enantiomeric excess (up to 20 %).

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“…1 Though seminal reports involved highly reactive organometallic nucleophiles, 2 systems were rapidly developed that involved functional-group-tolerant organoboron nucleophiles. Namely, Hayashi pioneered the use of rhodium/BINAP catalysts for the asymmetric conjugate addition of a number of boron-derived nucleophiles.…”

Section: Introductionmentioning

confidence: 99%

Mechanism and Enantioselectivity in Palladium-Catalyzed Conjugate Addition of Arylboronic Acids to β-Substituted Cyclic Enones: Insights from Computation and Experiment

et al. 2013

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Enantioselective conjugate additions of arylboronic acids to β-substituted cyclic enones have been reported previously from our laboratories. Air and moisture tolerant conditions were achieved with a catalyst derived in situ from palladium(II) trifluoroacetate and the chiral ligand (S)-t-BuPyOx. We now report a combined experimental and computational investigation on the mechanism, the nature of the active catalyst, the origins of the enantioselectivity, and the stereoelectronic effects of the ligand and the substrates of this transformation. Enantioselectivity is controlled primarily by steric repulsions between the t-Bu group of the chiral ligand and the α-methylene hydrogens of the enone substrate in the enantiodetermining carbopalladation step. Computations indicate that the reaction occurs via formation of a cationic arylpalladium(II) species, and subsequent carbopalladation of the enone olefin forms the key carbon-carbon bond. Studies of non-linear effects and stoichiometric and catalytic reactions of isolated (PyOx)Pd(Ph)I complexes show that a monomeric arylpalladium-ligand complex is the active species in the selectivity-determining step. The addition of water and ammonium hexafluorophosphate synergistically increases the rate of the reaction, corroborating the hypothesis that a cationic palladium species is involved in the reaction pathway. These additives also allow the reaction to be performed at 40 °C and facilitate an expanded substrate scope.

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Enantioselective palladium-catalysed conjugate addition of arylsiloxanes

Abstract: The complex formed from Pd(CH(3)CN)(4)(BF(4))(2) and (R,R)-MeDUPHOS is a highly enantioselective catalyst for the asymmetric conjugate addition of aryltriethylsiloxanes to a variety of unsaturated ketones, lactones and lactams.

Cited by 49 publications

References 31 publications

Palladium(II)-Catalyzed Alkene Functionalization via Nucleopalladation: Stereochemical Pathways and Enantioselective Catalytic Applications

Palladium(II)-Catalyzed Alkene Functionalization via Nucleopalladation: Stereochemical Pathways and Enantioselective Catalytic Applications

Importance of the Reducing Agent in Direct Reductive Heck Reactions

Mechanism and Enantioselectivity in Palladium-Catalyzed Conjugate Addition of Arylboronic Acids to β-Substituted Cyclic Enones: Insights from Computation and Experiment

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