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A major topic of this blog has been the growing body of studies that demonstrate that dynamic effects can control reaction products (see these posts). Often these examples crop up with valley ridge inflection points. Another cause can be bispericyclic transition states, first discovered by Caramella et al for the dimerization of cyclopentadiene.1 The Houk group now reports on the first trispericyclic transition state.2

Using B97X-D/6-31G(d),they examined the reaction of the tropone derivative 1 with dimethylfulvene2. Three possible products canarrive from different pericyclic reactions: 3, the [4+6] product; 4, the [6+4] product; and 5, the [8+2] product. The thermodynamicproduct is predicted to be 5, but it is only 1.2 kcal mol-1 lower in energythan 4 and 6.2 kcal mol-1lower than 3.

They identified one transition state originating from thereactants TS1. Hypothesizing that itwould be trispericyclic, they performed a moleculardynamics study with trajectories starting from TS1. They ran a total of 142 trajectories,and 87% led to 3, 3% led to 4, and 3% led to 5. This demonstrates the unusual nature of TS1 and the dynamic effects on this reaction surface.




Figure 1. B97X-D/6-31G(d) optimized geometries of TS1-TS3.

Additionally, there are two different Cope rearrangements(through TS2 and TS3) that convert 3 into 4 and 5. Some trajectoriescan pass from TS1 and then directly througheither TS2 or TS3 and these give rise to products 4 and 5. In other words,some trajectories will pass from a trispericyclic transition state and then through a bispericyclictransition state before ending in product.


1. Caramella,P.; Quadrelli, P.; Toma, L., “An Unexpected Bispericyclic TransitionStructure Leading to 4+2 and 2+4 Cycloadducts in the Endo Dimerization ofCyclopentadiene.” J. Am. Chem. Soc. 2002, 124, 1130-1131, DOI: 10.1021/ja016622h

2. Xue,X.-S.; Jamieson, C. S.; Garcia-Borrs, M.; Dong, X.; Yang, Z.; Houk, K. N.,“Ambimodal Trispericyclic Transition State and Dynamic Control ofPeriselectivity.” J. Am. Chem. Soc. 2019, 141, 1217-1221, DOI: 10.1021/jacs.8b12674.


1: InChI=1S/C10H6N2/c11-7-10(8-12)9-5-3-1-2-4-6-9/h1-6H

2: InChI=1S/C8H10/c1-7(2)8-5-3-4-6-8/h3-6H,1-2H3

3: InChI=1S/C18H16N2/c1-11(2)17-15-7-8-16(17)14-6-4-3-5-13(15)18(14)12(9-19)10-20/h3-8,13-16H,1-2H3

4: InChI=1S/C18H16N2/c1-18(2)13-6-8-14(12(10-19)11-20)15(9-7-13)16-4-3-5-17(16)18/h3-9,13,15-16H,1-2H3

5: InChI=1S/C18H16N2/c1-12(2)13-8-9-16-17(13)14-6-4-3-5-7-15(14)18(16,10-19)11-20/h3-9,14,16-17H,1-2H3/t14?,16-,17-/m1/s1

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Xue, X.-S.; Jamieson, C. S.; Garcia-Borrs, M.; Dong, X.; Yang, Z.; Houk, K. N., J. Am. Chem. Soc. 2019, 141, 1217Contributed by Steven BachrachReposted from Computational Organic Chemistry with permissionA major topic of this blog has been the growing body...