Critical distance model for the energy of activation of the Bergman cyclization of enediynes

Abstract

ABSTRACT:The reaction profile of the Bergman cyclization of enediynes is written as a cubic polynomial expansion about the critical distance. Using the "simple sewing" approximation, a relationship is derived that expresses the energy of activation as a function of the critical distance, with the effect of other geometric and electronic factors accounted for in the expansion coefficients. A training set of 10 representative enediynes were selected and input parameters were calculated by density functional theory at the B3LYP/6-311G* level of theory. All calculations were corrected for zero-point energy. All singlet biradical calculations were also checked for wave function stability. Calibration curves were then constructed that correlate the activation energy of cyclization of the molecules in the test set with the critical distance parameter.

Concerted Reactions That Produce Diradicals and Zwitterions: Electronic, Steric, Conformational, and Kinetic Control of Cycloaromatization Processes

“…As mentioned above, the 3.31–3.20 Å “critical C 1 –C 6 distance” was suggested by Nicolaou as a threshold separating unreactive enediynes from enediynes, which cyclize at ambient conditions . Subsequent ab initio computations showed that acceleration of the Bergman cyclization in cyclic enediynes can be modeled to a large extent by a simple decrease of the C 1 –C 6 distance in the parent acyclic enediyne; thus, the intrinsic properties of the enediyne moiety rather than the strain in the saturated (−CH 2 −) n bridges account for a large part of the reactant destabilization .…”

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

“…It is those diradicals that do not have any mechanism of self-quenching that become diamagnetic via abstraction of atoms from external sources. Bergman cyclization (BC) and related reactions such as Myers−Saito (MS) cyclization belong to this category. On the other hand, reactions such as Garratt−Braverman (GB) cyclization involving conjugated bisallenes (Scheme ) have a self-quenching mechanism, and hence, the chances of interaction with external sources are slim.…”

Design, Synthesis, and Biological Activity of Unnatural Enediynes and Related Analogues Equipped with pH-Dependent or Phototriggering Devices

“…The chemistry of the triggering or activation process for the natural enediynes primarily involves a change of hybridization at a carbon center encompassing the enediyne moiety or an opening of the epoxide ring fused onto the enediyne in bi- or tricyclic fashion (shown in Schemes and , respectively). This structural change is believed to lower the activation barrier for the cycloaromatization process either by bringing the terminal acetylenic carbon atoms (the c and d distance) closer or by easing the overall conformational restrictions …”