Organometallic Chemistry

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 the ring-expanded products due to the formal 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 furan, 2-methylfuran, 2,3-dimethylfuran and 2-methoxyfuran proceeded between 25 and 80 ºC leading to ring-expanded and 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 a-migration. The selectivity of ring-expansion is influenced by factors that weaken the sp2 C–O bond through population of the s*-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 but also improves the selectivity. Under catalysed conditions, the C–O bond that breaks is that adjacent to C–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 of the Pd-catalysed reaction of 1 with furan 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 proceeds with a strong primary KIE of 4.8 ± 0.3 consistent with a turnover limiting step involving oxidative addition of the C–H bond to a 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 the upgrading of molecules derived from furfuraldehyde, an important platform chemical from biomass.

Version notes

version 2 - revision


Thumbnail image of _C–O_Alumination_Furans_23May.pdf

Supplementary material

Thumbnail image of _SI_Me_Furan_23May.pdf
SI Me Furan 23May