Catalyst control of selectivity in the C-O bond alumination of biomass derived furans

Thomas N Hooper; Ryan K Brown; Feriel Rekhroukh; Martí Garçon; Andrew J P White; Paulo J Costa; Mark R Crimmin

doi:10.1039/d0sc01918f

Catalyst control of selectivity in the C-O bond alumination of biomass derived furans

Chem Sci. 2020 Jul 8;11(30):7850-7857. doi: 10.1039/d0sc01918f.

Authors

Thomas N Hooper¹, Ryan K Brown¹, Feriel Rekhroukh^{1

2}, Martí Garçon¹, Andrew J P White¹, Paulo J Costa², Mark R Crimmin¹

Affiliations

¹ Department of Chemistry, Molecular Sciences Research Hub, Imperial College London 80 Wood Lane, Shepherds Bush London W12 0BZ UK m.crimmin@imperial.ac.uk.
² BioISI - Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisboa 1749-016 Lisboa Portugal.

Abstract

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.