Alkoxyallene-Based LANCA Three-Component Synthesis of 1,2-Diketones, Quinoxalines, and Unique Isoindenone Dimers and a Computational Study of the Isoindenone Dimerization

Article abstract of DOI:10.1002/ejoc.202000116

A series of β-alkoxy-β-ketoenamides was prepared by the well-established LANCA three-component reaction of lithiated 1-(2-trimethylsilylethoxy)-substituted allenes, nitriles, and α,β-unsaturated carboxylic acids. The α-tert-butyl-substituted compounds were smoothly converted into the expected 1,2-diketones by treatment with trifluoroacetic acid. A subsequent condensation of the 1,2-diketones with o-phenylenediamine provided the desired highly substituted quinoxalines in good overall yield. Surprisingly, the α-phenyl-substituted β-alkoxy-β-ketoenamides investigated afford not only the expected 1,2-diketones, but also pentacyclic compounds with an anti-tricyclo[4.2.1.1^2,5]deca-3,7-diene-9,10-dione core. These interesting products are very likely the result of an isoindenone dimerization which was mechanistically studied with the support of DFT calculations. Under the strongly acidic reaction conditions, a stepwise reaction is likely leading to a protonated isoindenone as reactive intermediate. It may first form a van der Waals complex with a neutral isoindenone before the two regio- and diastereoselective ring forming steps occur. Interestingly, two neutral or two protonated isoindenones are also predicted to dimerize giving the observed pentacyclic product.||||||.