Physical Organic and Mechanistic Chemistry

In our group, we use high level ab initio and density functional calculations to provide fundamental insights into two classes of reactions, pseudopericyclic and pericyclic. We then design and conduct experiments to test the predictions of these calculations. The synergy between theory and experiment has provided insights and research directions that would not be possible from either alone.

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Pseudopericyclic Reactions

The "conventional wisdom" of the orbital symmetry rules tells an organic chemist what to expect from a pericyclic reaction. Pseudopericyclic reactions violate all of these expectations of a pericyclic reaction, yet strictly speaking they are orbital symmetry allowed. The fundamental difference between the two is that in a pseudopericyclic reaction, there is not orbital overlap around the ring of breaking and forming bonds. This allows their transition states to have a planar geometry, and, often, very low activation barriers.The difference between a planar pseudopericyclic transition state and a non-planar pseudopericyclic one is illustrated in two animations of these reaction pathways. The dramatic differences in geometries between them are summarized below.

The nature of a pseudopericyclic reaction is illustrated by the rearrangement of cyclohexadienyl esters. Our ab initio calculations indicate that this reaction proceeds directly to the observed product via an unusual [3,5]-sigmatropic rearrangement, rather than the two expected sequential [3,3]-rearrangements. Significantly, the calculated transition structure is completely planar at the ester, in contrast to most other pericyclic reactions. The planarity and [3,5] geometry are possible because of the presence of orthogonal orbitals in the ester. The orbital interactions in the transition structure are shown below.

Stereochemical studies have provided among the most detailed, albeit indirect insights into transition state geometries. Unfortunately, there are few stereochemical markers at the orbital orthogonalities in pseudopericyclic reactions. We have used a different approach to verify the predicted planar geometries of pseudopericyclic transition states, namely X-ray crystallography. The ground states of several molecules that can undergo pseudopericyclic reactions have been shown to be distorted towards fragmentation via a planar pathway. For example, the Figure below summarizes the results of an analysis of the X-ray structure of the dimer of camphorketene. Figure A shows the observed bond distances, Figure B shows the deviations in the bond angles as compared to model systems, and Figure C shows deviations in the bond lengths as compared to model systems. Note that the deviations in bond lengths and angles are not consistent with the effects of strain, but instead prefigure the fragmentation.

Sequential Transition States

We have recently begun studying reactions in which two distinct transition states are directly connected on the reaction potential energy surface (PES) without intervening intermediates. This is illustrated in a generic fashion in the figure below. From transition state 1, it is downhill to transition state 2, following the intrinsic reaction coordinate (IRC, in red). However, the IRC leads to a second transition state, not a product. One can envision leaving transition state 1 in a valley on a three-dimensional PES. But following the IRC to transition state 2 clearly leads down along a ridge. The point where the valley opens into a ridge is the valley-ridge inflection point (VRI). From the point of view of chemical dynamics, the VRI is a bifurcation point, past which the reaction paths can lead to either of two products.

We recently reported an example of sequential transition states in the deazetization of nitrosimines. [Bartsch, R. A.; Chae, Y. M.; Ham, S.; Birney, D. M., J. Am. Chem. Soc. 2001, 123, 7479-7486] In this case, the transition state (TS1) for rotation around the C=N bond connects to the transition state (TS2) for pseudopericyclic electrocyclization of 1 to the spiro intermediate (2, Figure and eq 1). In principle, ring-opening of oxetene (3) could proceed via an analogous two-stage process, with a planar, pseudopericyclic transition state connecting to a transition state for rotation around the C4-C3 bond. However, it is calculated to be concerted (eq 2). The difference between the two systems is that the barriers for rotation around the C4=C3 bond in acrolein (4) is much higher than for 1; thus there is an energetic benefit to concerted twisting in the ring-opening of oxetene (3), which allows for partial p-overlap in the transition state. Thus the ring closure of 1 to 2 may be considered to have separated the two fundamental processes that contribute to the concerted, pericyclic electrocyclic ring closure of butadiene, namely rotation and bond formation. Studies of additional potential energy surfaces that may have sequential transition states are currently underway in our group.

Multiphoton Infrared (MP-IR) Photolysis/Thermolysis

Multiphoton infrared (MP-IR) irradiation can be used to carry out gas-phase pyrolysis of molecules while avoiding subsequent thermal reactions of the product(s). We refer to this as MP-IR photolysis/thermolysis; it is a photolysis because of the absorption of IR photons, but it is a thermolysis because the chemistry occurs via thermally excited ground state molecules. MP-IR photolysis/thermolysis is initiated by the sequential absorption of IR photons from a pulsed IR laser. Thus, molecules that absorb the IR get hot. However, this process can be extremely selective and almost gentle. By tuning the IR laser and by judicious choice of reactants, only one component of a gas mixture may absorb the light and be heated. This molecule can either react or be cooled by collisions with cold molecules. The important point for this work is that these collisions can also cool hot product molecules before they can react further. This amounts to a pyrolysis in a room temperature environment.

Conventional heating of cis-2,5-dimethyl-3-cyclopentenone leads to loss of carbon monoxide, but also to scrambling of the products. There is no conventional technique that can distinguish which product is the first-formed one. Knowing this information would provide confirmation of the predicted stereochemistry of this pericyclic cheletropic reaction. 

We recently reported the results of MP-IR photolysis/thermolysis of cis-2,5-dimethyl-3-cyclopentenone. The only product is trans,trans-2,4-hexadiene, formed by the disrotatory pathway, as predicted by Woodward and Hoffmann over 30 years ago.

 Interestingly, a survey of crystal structures from the Cambridge Structural Database reveals ground state distortions along this reaction coordinate as well. This is not unprecedented. We have also shown that Diels-Alder adducts that are constrained to boat geometries can be distorted along a retro-Diels-Alder pathway. This work builds on the well-known example in which X-ray structures prefigure transition states; the Burgi-Dunitz trajectory for the addition of nucleophiles to carbonyls.

• “Photochemical Dehydration of Acetamide In a Cryogenic Matrix”, F. Duvernay, P. Chatron-Michaud, F. Borget, D. Birney and T. Chiavassa Phys. Chem. Chem. Phys. 2007. Accepted for publication.
• “Stopped-flow kinetics of tetrazine cycloadditions; Experimental and computational studies towards sequential transition states”, Dhandapani V. Sadasivam, Edamana Prasad, Robert A. Flowers II, David M. Birney J. Phys. Chem. 2006, 110(4) 1288-1294. An invited contribution to the William Hase Festschrift.
• "A Theoretical Study of the [4 + 4] Dimerization of Thioformylketene", Sadasivam, D.V.; Birney, D.M.  Org. Lett. 2005, 7, 5817-5820.

• “Experimental Support For Planar Pseudopericyclic Transition States In Thermal Cheletropic Decarbonylations”, Wei, H.-X.;  Zhou, C.;  Ham, S.; White, J.M.; Birney, D.M.  Org. Lett. 2004, 6, 4289-4292.

• “Experimental and Theoretical Studies of the Dimerizations of Imidoylketenes”, Zhou, C.; Birney, D.M.  J. Org. Chem. 2004, 69, 86-94.

• “Nitrosation of Amides Involves a Pseudopericyclic 1,3-sigmatropic Rearrangement”, Birney, D.M. Org. Lett. 2004, 6, 851-854.

• “a,5-Didehydro-3-picoline Diradicals from Skipped Aza-Enediynes:  Computational and Trapping Studies of an Aza-Myers-Saito Cyclization.”, Feng, L.; Kumar, D.; Birney, D.M.; Kerwin, S.M. Org. Lett. 2004, 6, 2059–2062.

• "The Stereochemistry of the Thermal Cheletropic Decarbonylation of 3-Cyclopentenone as Determined by Multiphoton Infrared Photolysis/Thermolysis," Unruh, G.R.; Birney, D.M., J. Am. Chem. Soc. 2003, 125, 8529 – 8533.

• "Sequential Transition States and the Valley-ridge Inflection Point in the Formation of a Semibullvalene," Zhou, C.; Birney, D.M., Org. Lett. 2002, 4, 3279-3282.

• "A DFT Study Clarifying the Reactions of Conjugated Ketenes with Formaldimine. A Plethora of Pericyclic and Pseudopericyclic Pathways," Zhou, C.; Birney, D.M., J. Am. Chem. Soc. 2002, 124, 5231-5241.

• "Structural Investigations Into the Retro Diels Alder Reaction. Experimental and Theoretical Studies," Birney, D,; Lim, T.K.; Peng, J.; Pool, B.R.; White, J.M., J. Am. Chem. Soc. 2002, 124, 5091-5099.