Dataset Information

Palladium-catalysed C-F alumination of fluorobenzenes: mechanistic diversity and origin of selectivity.

ABSTRACT: A palladium pre-catalyst, [Pd(PCy₃)₂] is reported for the efficient and selective C-F alumination of fluorobenzenes with the aluminium(i) reagent [{(ArNCMe)₂CH}Al] (1, Ar = 2,6-di-iso-propylphenyl). The catalytic protocol results in the transformation of sp² C-F bonds to sp² C-Al bonds and provides a route to reactive organoaluminium complexes (2a-h) from fluorocarbons. The catalyst is highly active. Reactions proceed within 5 minutes at 25 °C (and at appreciable rates at even -50 °C) and the scope includes low-fluorine-content substrates such as fluorobenzene, difluorobenzenes and trifluorobenzenes. The reaction proceeds with complete chemoselectivity (C-F vs. C-H) and high regioselectivities (>90% for C-F bonds adjacent to the most acidic C-H sites). The heterometallic complex [Pd(PCy₃)(1)₂] was shown to be catalytically competent. Catalytic C-F alumination proceeds with a KIE of 1.1-1.3. DFT calculations have been used to model potential mechanisms for C-F bond activation. These calculations suggest that two competing mechanisms may be in operation. Pathway 1 involves a ligand-assisted oxidative addition to [Pd(1)₂] and leads directly to the product. Pathway 2 involves a stepwise C-H → C-F functionalisation mechanism in which the C-H bond is broken and reformed along the reaction coordinate, guiding the catalyst to an adjacent C-F site. This second mechanism explains the experimentally observed regioselectivity. Experimental support for this C-H activation playing a key role in C-F alumination was obtained by employing [{(MesNCMe)₂CH}AlH₂] (3, Mes = 2,4,6-tri-methylphenyl) as a reagent in place of 1. In this instance, the kinetic C-H alumination intermediate could be isolated. Under catalytic conditions this intermediate converts to the thermodynamic C-F alumination product.

SUBMITTER: Rekhroukh F

PROVIDER: S-EPMC8163258 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Non-catalysed and catalysed reactions of aluminium reagents with furans, dihydrofurans and dihydropyrans were investigated and lead to ring-expanded products due to the insertion of the aluminium reagent into a C-O bond of the heterocycle. Specifically, the reaction of [{(ArNCMe)2CH}Al] (Ar = 2,6-di-iso-propylphenyl, 1) with furans proceeded between 25 and 80 °C leading to dearomatised products due to the net transformation of a sp2 C-O bond into a sp2 C-Al bond. The kinetics of the reaction of 1 with furan were found to be 1st order with respect to 1 with activation parameters ΔH ‡ = +19.7 (±2.7) kcal mol-1, ΔS ‡ = -18.8 (±7.8) cal K-1 mol-1 and ΔG ‡ 298 K = +25.3 (±0.5) kcal mol-1 and a KIE of 1.0 ± 0.1. DFT calculations support a stepwise mechanism involving an initial (4 + 1) cycloaddition of 1 with furan to form a bicyclic intermediate that rearranges by an α-migration. The selectivity of ring-expansion is influenced by factors that weaken the sp2 C-O bond through population of the σ*-orbital. Inclusion of [Pd(PCy3)2] as a catalyst in these reactions results in expansion of the substrate scope to include 2,3-dihydrofurans and 3,4-dihydropyrans and improves selectivity. Under catalysed conditions, the C-O bond that breaks is that adjacent to the sp2C-H bond. The aluminium(iii) dihydride reagent [{(MesNCMe)2CH}AlH2] (Mes = 2,4,6-trimethylphenyl, 2) can also be used under catalytic conditions to effect a dehydrogenative ring-expansion of furans. Further mechanistic analysis shows that C-O bond functionalisation occurs via an initial C-H bond alumination. Kinetic products can be isolated that are derived from installation of the aluminium reagent at the 2-position of the heterocycle. C-H alumination occurs with a KIE of 4.8 ± 0.3 consistent with a turnover limiting step involving oxidative addition of the C-H bond to the palladium catalyst. Isomerisation of the kinetic C-H aluminated product to the thermodynamic C-O ring expansion product is an intramolecular process that is again catalysed by [Pd(PCy3)2]. DFT calculations suggest that the key C-O bond breaking step involves attack of an aluminium based metalloligand on the 2-palladated heterocycle. The new methodology has been applied to important platform chemicals from biomass.

Dataset Information

Palladium-catalysed C-F alumination of fluorobenzenes: mechanistic diversity and origin of selectivity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets