Monocyclic Enediynes:  Relationships between Ring Sizes, Alkyne Carbon Distances, Cyclization Barriers, and Hydrogen Abstraction Reactions. Singlet−Triplet Separations of Methyl-Substituted <i>p</i>-Benzynes

The Bergman-type cyclizations of parent, 2,3-dimethyl, and monocyclic (ring sizes = 7−12) enediynes were studied in detail at the Becke−Lee−Yang−Parr (BLYP) density functional (DFT) level with 6-31G* as well as 6-311+G** basis sets for geometry optimizations and relative energy evaluations, respectively. Pure DFT methods work reasonably well for these reactions; the errors are somewhat larger (ca. 3−7 kcal mol^-1) than for the much more time-consuming complete active space (CASPT2) and coupled-cluster [CCSD(T)] (both in error by ca. 2 kcal mol^-1) methods with high-quality basis sets. The hybrid method B3LYP is unsuitable for this type of chemistry (errors of 14−20 kcal mol^-1). The singlet−triplet energy separations (Δ<i>E</i>_ST) for <i>p</i>-benzynes are underestimated systematically by about 2 kcal mol^-1 at BLYP; the Δ<i>E</i>_ST of 2-methyl-<i>p</i>-benzyne (−3.1 kcal mol^-1) is close to that of <i>p</i>-benzyne (−3.8 kcal mol^-1, i.e., singlet ground state) but the 2,3-dimethyl-<i>p</i>-benzyne Δ<i>E</i>_ST is only −0.6 kcal mol^-1 due to singlet destabilization (methyl repulsion). 2,3-Dialkyl-<i>p</i>-benzynes thus have nearly degenerate singlet and triplet states. While we find that there is clearly no predictive relationship between the alkyne carbon distance (<i>d</i>) and the cyclization activation enthalpy (Δ<i>H</i>^⧧) for monocyclic enediynes, Nicolaou's empirically determined “critical range” of 3.31−3.2 Å, where spontaneous cyclization should occur at room temperature, should be extended to 3.4−2.9 Å. However, ring strain effects may become more important than distance arguments. Dimethyl substitution increases the endothermicity of the Bergman reaction (by about 12 kcal mol^-1). The cyclization of a nine-membered enediyne is only mildly endothermic; larger rings give larger endothermicities. The formation of final products via double hydrogen abstraction from 1,4-cyclohexadiene is highly exothermic. The exothermicity decreases with increasing ring size due to unfavorable H···H repulsion in the products.