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)(2)CH}Al] (Ar = 2,6-di-iso-propylphenyl,1) with furans proceeded between 25 and 80 degrees C leading to dearomatised products due to the net transformation of a sp(2)C-O bond into a sp(2)C-Al bond. The kinetics of the reaction of1with furan were found to be 1st order with respect to1with activation parameters Delta H-double dagger= +19.7 (+/- 2.7) kcal mol(-1), Delta S-double dagger= -18.8 (+/- 7.8) cal K(-1)mol(-1)and Delta G double dagger 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 of1with furan to form a bicyclic intermediate that rearranges by an alpha-migration. The selectivity of ring-expansion is influenced by factors that weaken the sp(2)C-O bond through population of the sigma*-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 sp(2)C-H bond. The aluminium(iii) dihydride reagent [{(MesNCMe)(2)CH}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 occursviaan 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.