López-Camacho Perla Y., Joseph-Nathan Pedro , Gordillo-Román Bárbara, Suárez-Castillo Oscar R., Morales-Ríos Martha S. Cascade [1,3]-sigmatropic rearrangements of ketene O,O-acetals: kinetic and DFT level mechanistic studies. J. Org. Chem. 75, 19111916 (2010). ISSN 0022-3263. DOI: 10.1021/jo902520z
The regioisomeric ?-cyano ketene-O,O-dialkyl acetals 2a?e and 4a?e, sequential intermediates in the diazomethane induced conversion of indole ?-cyano-?-lactones 1a?e to 2-indolyl cyanomalonates 5a?e, were isolated and characterized. Formation of the steady-state intermediate cycloprop[b]indoles 3a?e was evidenced by means of NMR and confirmed by the X-ray structure of 3c, demonstrating that the formation of 5a?e from 2a?e proceeds through two consecutive and one parallel unimolecular steps, with intermediates 3a?e formed in reversible processes. Evidence that the reversible reactions proceed via [1,3]-rearrangements is presented. The steady-state kinetic approach applied to intermediate 3 allowed a minimal two consecutive step 2 ? 4? 5 kinetic model, in which the steric bulkiness of the alkyl substituent affects strongly the associated rate constants, k1 and k2, inverting the rate-determining step. The solvation effects enhanced the feasibility of these skeletal rearrangements as they stabilized the transition states to a great extent. The experimental determined thermodynamic parameters and DFT calculations suggest that these cascade rearrangements occur through [1,3]-sigmatropic mechanisms, in which asynchronous bond reorganization processes via four membered pseudopericyclic transition states are highly favorable.