Cascade [1,3]-sigmatropic rearrangements of ketene O,O-acetals: kinetic and DFT level mechanistic studies.
The regioisomeric alpha-cyano ketene-O,O-dialkyl acetals 2a-e and 4a-e, sequential intermediates in the diazomethane induced conversion of indole alpha-cyano-gamma-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, k(1) and k(2), 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.
López-Camacho
Perla Y
PY
Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, México, DF, 07000 Mexico.
Joseph-Nathan
Pedro
P
Gordillo-Román
Bárbara
B
Suárez-Castillo
Oscar R
OR
Morales-Ríos
Martha S
MS
D000080:Acetals / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003978:Diazomethane / Q000737:chemistry; D005030:Ethylenes / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D011789:Quantum Theory; D013816:Thermodynamics
D000080:Acetals; D005030:Ethylenes; D007659:Ketones; D003978:Diazomethane; C008223:ketene; D010100:Oxygen