Efficient construction of novel carbocyclic frameworks via intramolecular aromatic addition of diazoketones followed by Diels-Alder cycloaddition

Abstract

Rhodium catalysed intramolecular aromatic additions of diazoketones followed by Diels-Alder cycloadditions with carbon-based dienophiles leads in a highly stereoselective manner to polycyclic frameworks containing eight stereogenic centres completely controlled by the single stereocentre present in the diazoketone precursor. These cycloadditions provide interesting mechanistic insight into a dynamic equilibrium in methoxy-substituted azulenones.

A study of the norcaradiene–cycloheptatriene equilibrium in a series of azulenones by NMR spectroscopy; the impact of substitution on the position of equilibrium

“…A series of azulenones with varying substituents R, R 2 and X, designed to enable exploration of the influence of substitution on the norcaradiene-cycloheptatriene tautomeric equilibrium, were prepared by efficient rhodium(II) catalysed cyclisation of the precursor α-diazoketones, derived from the appropriate carboxylic acid, following previously reported methodology (Scheme 4). 42,43,45,46 With substituents (R) in the linker chain of the diazoketones, the resulting azulenones can be formed in two diastereomeric forms. In practice, the major diastereomer of azulenones substituted at C-2 is the cis-azulenone (C-2 relative to C-8a) while the trans-azulenone (C-3 relative to C-8a) is the major product of the C-3 substituted azulenones due to a conformational preference in the transition states for the aromatic addition.…”