Cycloadditions of Cyclopentadiene and Cycloheptatriene with Tropones: All Endo-[6+4] Cycloadditions Are Ambimodal

Abstract

The cycloadditions of cyclopentadiene and cycloheptatriene with tropone are some of the earliest published examples of [6+4] cycloaddition reactions. We report quantum mechanical studies (ωB97X-D and DLPNO-CCSD(T)) of transition structures and products of these reactions, as well as quasi-classical molecular dynamics simulations of reaction trajectories. The study reveals that these cycloadditions involve ambimodal transition states resulting in a web of products by pericyclic interconversion pathways. Combined with these studies, calculations of simple parent systems and a thorough meta-analysis of literature examples reveal the general concept that all endo-[6+4] cycloadditions are ambimodal.

Bifurcating reactions: distribution of products from energy distribution in a shared reactive mode

“…In all these cases, the rmcf.py program does not predict any propensity for formation of the bond leading to product C in line with MD carried out by Houk and coworkers, which yielded 1% of 59C , 1% of 60C and 0% of 61C . 65 Hence, we treated these reactions as bifurcations, obtaining ratios of 39% : 61% ( vs. Houk's MD ratio of 36% : 58% for 59A : 59B ), 42% : 58% ( vs. 63% : 30% for 60A : 60B ) and 36% : 64% ( vs. 55% : 37% for 61A : 61B ). The origin of the discrepancies for 60 and 61 is unclear but it is likely is a consequence of steric interactions, as the authors mention in the original work, and which would be consistent with the erroneous prediction of the major product in reaction 5 (see the section Advantages and limitations of RMCF).…”

“…As such, reactions 1-48 served as a training set for the model. Next, we proceed to evaluate its performance on a test set of 13 additional reactions, 49-61, 64,65,66,67,68,69,70 shown in Figure 5. is carried out according to the description in Scheme 2.…”

“…An alternative approach put forward by Houk correlates bond order differences at TS 1 with the product ratio, 20 fitting a linear function to data from a set of 15 reactions. Although purely empirical, this model has been tested on several examples with positive results, 21,22,23 demonstrating that TS 1 contains information which, if decoded, allows to make predictions on bifurcating energy surfaces. Recently, Goodman et al…”

Computations on Pericyclic Reactions Reveal the Richness of Ambimodal Transition States and Pericyclases

“…An attractive and exciting area of research is to modulate the ambimodal tetrapericyclic transition structure that enables access to complex ring systems which are difficult to obtain by other means. [22]…”

A new cycloaddition profile for ortho-quinone methides: photoredox-catalyzed [6+4] cycloadditions for synthesis of benzo[b]cyclopenta[e]oxepines

“…When medium- to non-polar solvents were used, the reaction proceeded to give the desired [6+4] cycloadduct ( 3a ) (entries 1–4). While several [6+4] cycloadditions of pentafulvene have been reported, 12 visible-light-induced cycloadditions have not yet been examined. EtOAc seems to be the most effective solvent and furnished 3a in 64% (entry 5).…”