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)CH}Al] (Ar = 2,6-di-iso-propylphenyl, ) with furans proceeded between 25 and 80 °C leading to dearomatised products due to the net transformation of a sp C-O bond into a sp C-Al bond. The kinetics of the reaction of with furan were found to be 1st order with respect to with activation parameters Δ = +19.7 (±2.7) kcal mol, Δ = -18.8 (±7.8) cal K mol and Δ = +25.3 (±0.5) kcal mol and a KIE of 1.0 ± 0.1. DFT calculations support a stepwise mechanism involving an initial (4 + 1) cycloaddition of 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 sp C-O bond through population of the σ*-orbital. Inclusion of [Pd(PCy)] 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 spC-H bond. The aluminium(iii) dihydride reagent [{(MesNCMe)CH}AlH] (Mes = 2,4,6-trimethylphenyl, ) 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 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(PCy)]. 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.