Issue 30, 2020

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


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 ΔG298 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.

Graphical abstract: Catalyst control of selectivity in the C–O bond alumination of biomass derived furans

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Article information

Article type
Edge Article
03 Apr 2020
03 Jul 2020
First published
08 Jul 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2020,11, 7850-7857

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

T. N. Hooper, R. K. Brown, F. Rekhroukh, M. Garçon, A. J. P. White, P. J. Costa and M. R. Crimmin, Chem. Sci., 2020, 11, 7850 DOI: 10.1039/D0SC01918F

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