Which One Is Preferred: Myers−Saito Cyclization of Ene-Yne-Allene or Garratt−Braverman Cyclization of Conjugated Bisallenic Sulfone? A Theoretical and Experimental Study

Abstract

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.

Reactivity of Bispropargyl Sulfones under Basic Conditions: Interplay Between Garratt–Braverman and Schmittel/Myers–Saito Cyclization Pathway

“…The results demonstrated that both sulfones have cleavage activity ( Figure 2). Although the cleavage efficiency of the aromatic sulfone 7 did not improve much, the aliphatic sulfone 8 showed much stronger DNA-cleaving activity (72 % at 20 mm relative to 10 % at 1 mm for acyclic sulfones as already reported [11] ).…”

“…Semmelhack et al [18] had previously reported the formation of a product that arose out of similar trapping with a phenyl radical. Now that we were able to switch the preference from GB to SCM or MS, these sulfones were expected to show better DNA-cleavage activity than that for earlier reported [11] similar compounds that undergo GB cyclization. Thus the sulfones 7 and 8 were incubated with pBR322 DNA at pH 8.5.…”

“…[19] Optimization of all groundstate geometries except phenyl-substituted systems were done using the M06-2X functional, [20] which accounts for the dispersive interaction. Like the previously reported work, [11] the B3LYP functional [21,22] was used for the phenyl-substituted system. The 6-31+G* basis set was used for all the calculations.…”

Laser desorption ionization mass spectrometry: Recent progress in matrix‐free and label‐assisted techniques

“…One example 62 is the controversy regarding the involvement of a monoallene or bis-allene during Garratt-Braverman cyclization of bis-propargyl ether or sulfone. 63,64 The allenes from bis-naphthyl ether and sulfone were trapped with methanol, and the reaction mixture was subjected to LALDI-MS. The bis-naphthyl system was chosen for this study because the naphthyl moiety can act as a label capable of absorbing the laser light.…”

Intracellular Fluorometric Recognition of Explosive and Mutagenic Nitroaromatics by a Luminescent Phenanthrene‐Naphthalene Sulfone

“…It has been observed that the emission of TNP treated cells are quenched ( Figure 5) which is in line with the experimentation. The outcome indicates that the chemosensor Br-LANS prepared by Garratt-Braverman cyclization [45] could be useful as biocompatible chemosensor for detection of TNP like lethal environment pollutant.…”