Which one is preferred: Myers-Saito cyclization of ene-yne-allene or Garratt-Braverman cyclization of conjugated bisallenic sulfone? A theoretical and experimental study.
A competitive scenario between Myers-Saito (MS) and Garratt-Braverman (GB) cyclization has been created in a molecule. High-level computations indicate a preference for GB over MS cyclization. The activation energies for the rate-determining steps of the GB and MS cyclizations were found to be the same (24.4 kcal/mol) at the B3LYP/6-31G* level of theory; thus, from the kinetic point of view, both reactions are feasible. However, the main biradical intermediate GB2 of the GB reaction is 6.2 kcal/mol lower in energy than the biradical MS2, which is the main intermediate of MS reaction, so GB cyclization is thermodynamically favored over MS cyclization. To verify the prediction by computational techniques, bisenediynyl sulfones 1-4 and bisenediynyl sulfoxide 17 were synthesized. Under basic conditions, these molecules isomerized to a system possessing both the ene-yne-allene and the bisallenic sulfone. The isolation of only one product, identified as the corresponding naphthalene- or benzene-fused sulfone 8-11, indicated the occurrence of GB cyclization as the sole reaction pathway. No product corresponding to the MS cyclization pathway could be isolated. Though the theoretical prediction showed a preference for the GB pathway over the MS pathway, the exclusive preference for GB over MS cyclization is very striking. Further analysis showed that the intramolecular self-quenching nature of the GB pathway may play an important role in the complete preference for this reaction. Apart from the mechanistic studies, these sulfones showed DNA cleavage activity that had an inverse relation with the reactivity order. Our findings are important for the design of artificial DNA-cleaving agents.
Basak
Amit
A
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India. absk@chem.iitkgp.ernet.in
Das
Sanket
S
Mallick
Dibyendu
D
Jemmis
Eluvathingal D
ED
D003500:Cyclization; D007700:Kinetics; D008962:Models, Theoretical; D013450:Sulfones / Q000737:chemistry*
D013450:Sulfones