Archive for the 'Authors' Category

Inverted Carbon Atoms

Inverted carbon atoms, where the bonds from a single carbon atom are made to four other atoms which all on one side of a plane, remain a subject of fascination for organic chemists. We simply like to put carbon into unusual environments! Bremer, Fokin, and Schreiner have examined a selection of molecules possessing inverted carbon atoms and highlights some problems both with experiments and computations.1

The prototype of the inverted carbon is propellane 1. The ­Cinv-Cinv bond distance is 1.594 Å as determined in a gas-phase electron diffraction experiment.2 A selection of bond distance computed with various methods is shown in Figure 1. Note that CASPT2/6-31G(d), CCSD(t)/cc-pVTZ and MP2 does a very fine job in predicting the structure. However, a selection of DFT methods predict a distance that is too short, and these methods include functionals that include dispersion corrections or have been designed to account for medium-range electron correlation.















Figure 1. Optimized Structure of 1 at MP2/cc-pVTZ, along with Cinv-Cinv distances (Å) computed with different methods.

Propellanes without an inverted carbon, like 2, are properly described by these DFT methods; the C-C distance predicted by the DFT methods is close to that predicted by the post-HF methods.

The propellane 3 has been referred to many times for its seemingly very long Cinv-Cinv bond: an x-ray study from 1973 indicates it is 1.643 Å.3 However, this distance is computed at MP2/cc-pVTZ to be considerably shorter: 1.571 Å (Figure 2). Bremer, Fokin, and Schreiner resynthesized 3 and conducted a new x-ray study, and find that the Cinv-Cinv distance is 1.5838 Å, in reasonable agreement with the computation. This is yet another example of where computation has pointed towards experimental errors in chemical structure.

Figure 2. MP2/cc-pVTZ optimized structure of 3.

However, DFT methods fail to properly predict the Cinv-Cinv distance in 3. The functionals B3LYP, B3LYP-D3BJ and M06-2x (with the cc-pVTZ basis set) predict a distance of 1.560, 1.555, and 1.545 Å, respectively. Bremer, Folkin and Schreiner did not consider the ωB97X-D functional, so I optimized the structure of 3 at ωB97X-D/cc-pVTZ and the distance is 1.546 Å.

Inverted carbon atoms appear to be a significant challenge for DFT methods.


(1) Bremer, M.; Untenecker, H.; Gunchenko, P. A.; Fokin, A. A.; Schreiner, P. R. "Inverted Carbon Geometries: Challenges to Experiment and Theory," J. Org. Chem. 2015, 80, 6520–6524, DOI: 10.1021/acs.joc.5b00845.

(2) Hedberg, L.; Hedberg, K. "The molecular structure of gaseous [1.1.1]propellane: an electron-diffraction investigation," J. Am. Chem. Soc. 1985, 107, 7257-7260, DOI: 10.1021/ja00311a004.

(3) Gibbons, C. S.; Trotter, J. "Crystal Structure of 1-Cyanotetracyclo[,7.03,7]decane," Can. J. Chem. 1973, 51, 87-91, DOI: 10.1139/v73-012.


1: InChI=1S/C5H6/c1-4-2-5(1,4)3-4/h1-3H2

3: InChI=1S/C11H13N/c12-7-9-1-8-2-10(4-9)6-11(10,3-8)5-9/h8H,1-6H2

Schreiner Steven Bachrach 06 Jul 2015 8 Comments

Dyotropic rearrangement

Houk and Vanderwal have examined the dyotropic rearrangement of an interesting class of polycyclic compounds using experimental and computational techniques.1 The parent reaction takes the bicyclo[2.2.2]octadiene 1 into the bicyclo[3.2.1]octadiene 3. The M06-2X/6-311+G(d,p)/B3LYP/6-31G(d) (with CPCM simulating xylene) geometries and relative energies are shown in Figure 1. The calculations indicate a stepwise mechanism, with an intervening zwitterion intermediate. The second step is rate determining.






Figure 1. B3LYP/6-31G(d) and relative energies (kcal mol-1) at M06-2X/6-311+G(d,p).

Next they computed the activation barrier for the second TS for a series of substituted analogs of 1, with various electron withdrawing group as R1 and electron donating groups as R2, and compared them with the experimental rates.

Further analysis was done by relating the charge distribution in these TSs with the relative rates, and they find a nice linear relationship between the charge and ln(krel). This led to the prediction that a cyano substituent would significantly activate the reaction, which was then confirmed by experiment. Another prediction of a rate enhancement with Lewis acids was also confirmed by experiment.

A last set of computations addressed the question of whether a ketone or lactone would also undergo this dyotropic rearrangement. The lactam turns out to have the lowest activation barrier by far.


(1) Pham, H. V.; Karns, A. S.; Vanderwal, C. D.; Houk, K. N. "Computational and Experimental Investigations of the Formal Dyotropic Rearrangements of Himbert Arene/Allene Cycloadducts," J. Am. Chem. Soc. 2015, 137, 6956-6964, DOI: 10.1021/jacs.5b03718.


1: InChI=1S/C11H11NO/c1-12-10(13)7-9-6-8-2-4-11(9,12)5-3-8/h2-5,7-8H,6H2,1H3

3: InChI=1S/C11H11NO/c1-12-10(13)6-9-3-2-8-4-5-11(9,12)7-8/h2-6,8H,7H2,1H3

Houk Steven Bachrach 29 Jun 2015 1 Comment

Making superacidic phenols

Kass and coworkers looked at a series of substituted phenols to tease out ways to produce stronger acids in non-polar media.1 First they established a linear relationship between the vibrational frequency shifts of the hydroxyl group in going from CCl4 as solvent to CCl4 doped with 1% acetonitrile with the experimental pKa in DMSO. They also showed a strong relationship between this vibrational frequency shift and gas phase acidity (both experimental and computed deprotonation energies).

A key recognition was that a charged substituent (like say ammonium) has a much larger effect on the gas-phase (and non-polar solvent) acidity than on the acidity in a polar solvent, like DMSO. This can be attributed to the lack of a medium able to stable charge build-up in non-polar solvent or in the gas phase. This led them to 1, for which B3LYP/6-31+G(d,p) computations of the analogous dipentyl derivative 2 (see Figure 1) indicated a deprotonation free energy of 261.4 kcal mol-1, nearly 60 kcal mol-1 smaller than any other substituted phenol they previously examined. Subsequent measurement of the OH vibrational frequency shift showed the largest shift, indicating that 1 is extremely acidic in non-polar solvent.

Further computational exploration led to 3 (see Figure 1), for which computations predicted an even smaller deprotonation energy of 231.1 kcal mol-1. Preparation of 4 and experimental observation of its vibrational frequency shift revealed an even larger shift than for 1, making 4 extraordinarily acidic.


Conjugate base of 2


Conjugate base of 3

Figure 1. B3LYP/6-31+G(d,p) optimized geometries of 2 and 3 and their conjugate bases.


(1) Samet, M.; Buhle, J.; Zhou, Y.; Kass, S. R. "Charge-Enhanced Acidity and Catalyst Activation," J. Am. Chem. Soc. 2015, 137, 4678-4680, DOI: 10.1021/jacs.5b01805.


1 (cation only): InChI=1S/C23H41NO/c1-4-6-8-10-12-14-20-24(3,21-15-13-11-9-7-5-2)22-16-18-23(25)19-17-22/h16-19H,4-15,20-21H2,1-3H3/p+1


3: InChI=1S/C6H7NO/c1-7-4-2-3-6(8)5-7/h2-5H,1H3/p+1

4 (cation only): InChI=1S/C13H21NO/c1-2-3-4-5-6-7-10-14-11-8-9-13(15)12-14/h8-9,11-12H,2-7,10H2,1H3/p+1

Acidity &Kass Steven Bachrach 02 Jun 2015 No Comments

Host-guest complexes

Grimme and coworkers have a featured article on computing host-guest complexes in a recent ChemComm.1 They review the techniques his group has pioneered, particularly dispersion corrections for DFT and ways to treat the thermodynamics in moving from electronic energy to free energy. they briefly review some studies done by other groups. They conclude with a new study of eight different host guest complexes, three of which are shown in Figure 1.




Figure 1. TPSS-D3(BJ)/def2-TZVP optimized structures of 1-3.

These eight host-guest complexes are fairly large systems, and the computational method employed means some fairly long computations. Geometries were optimized at TPSS-D3(BJ)/def2-TZVP, then single point energy determined at PW6B95-D3(BJ)/def2-QZVP. Solvent was included using COSMO-RS. The curcurbituril complex 2 includes a counterion (chloride) along with the guest adamantan-1-aminium. Overall agreement of the computed free energy of binding with the experimental values was very good, except for 3 and the related complex having a larger nanohoop around the fullerene. The error is due to problems in treating the solvent effect, which remains an area of real computational need.

An interesting result uncovered is that the binding energy due to dispersion is greater than the non-dispersion energy for all of these complexes, including the examples that are charged or where hydrogen bonding may be playing a role in the bonding. This points to the absolute necessity of including a dispersion correction when treating a host-guest complex with DFT.

As an aside, you’ll note one of the reasons I was interested in this paper: 3 is closely related to the structure that graces the cover of the second edition of my book.


(1) Antony, J.; Sure, R.; Grimme, S. "Using dispersion-corrected density functional theory to understand supramolecular binding thermodynamics," Chem. Commun. 2015, 51, 1764-1774, DOI: 10.1039/C4CC06722C.

Grimme &host-guest Steven Bachrach 12 May 2015 1 Comment

Molecular rotor and C-Hπ interaction

Molecular rotors remain a fascinating topic – the idea of creating a miniature motor just seems to capture the imagination of scientists. Garcia-Garibay and his group have synthesized the interesting rotor 1, and in collaboration with the Houk group, they have utilized computations to help understand the dynamics of this rotor.1


The x-ray structure of this compound, shown in Figure 1, displays two close interactions of a hydrogen on the central phenyl ring with the face of one of the steroidal phenyl rings. Rotation of the central phenyl ring is expected to then “turn off” one or both of these C-Hπ interactions. The authors argue this as a competition between the molecule sampling an enthalpic region, where the molecule has one or two favorable C-Hπ interactions, and the large entropic region where these C-Hπ interactions do not occur, but this space is expected to have a large quantity of energetically similar conformations.




Figure 1. X-ray and M06-2x/6-31G(d) optimized structures of 1.

Variable temperature NMR finds the central phenyl hydrogen with a chemical shift of 6.55ppm at 295 K but at 6.32 ppm at 222 K. This suggest as freezing of the conformations at low temperature favoring those conformations possessing the internal C-Hπ interactions. M06-2X/6-31G(d) optimization finds two low-energy conformations with a single C-Hπ interaction. These are shown in Figure 1. No competing conformation was found to have two such interactions. Computations of the chemical shifts of these conformations show the upfield shift of the central phenyl hydrogens. Fitting these chemical shifts to the temperature data gives ΔH = -1.74 kcal mol-1, ΔS = -5.12 esu and ΔG = -0.21 kcal mol-1 for the enthalpic region to entropic region transition.


(1) Pérez-Estrada, S.; Rodrı́guez-Molina, B.; Xiao, L.; Santillan, R.; Jiménez-Osés, G.; Houk, K. N.; Garcia-Garibay, M. A. "Thermodynamic Evaluation of Aromatic CH/π Interactions and Rotational Entropy in a Molecular Rotor," J. Am. Chem. Soc. 2015, 137, 2175-2178, DOI: 10.1021/ja512053t.


1: InChI=1S/C48H54O4/c1-45-23-19-39-37-15-11-35(51-3)29-33(37)9-13-41(39)43(45)21-27-47(45,49)25-17-31-5-7-32(8-6-31)18-26-48(50)28-22-44-42-14-10-34-30-36(52-4)12-16-38(34)40(42)20-24-46(44,48)2/h5-8,11-12,15-16,29-30,39-44,49-50H,9-10,13-14,19-24,27-28H2,1-4H3

Aromaticity &Houk &Hydrogen bond Steven Bachrach 23 Mar 2015 No Comments

Two review articles for the general audience

In trying to clean up my in-box of articles for potential posts, I write here about two articles for a more general audience, authored by two of the major leaders in computational organic chemistry.

Ken Houk offers an overview of how computational simulation is a partner with experiment and theory in aiding and guiding our understanding of organic chemistry.1 The article is written for the non-specialist, really even more for the non-scientist. Ken describes how computations have helped understand relatively simple reactions like pericyclic reactions, that then get more subtle when torquoselection is considered, to metal-catalysis, to designed protein catalysts. If you are ever faced with discussing just what you do as a computational chemist at a cocktail party, this article is a great resource of how to explain our science to the interested lay audience.

Paul Schleyer adds a tutorial on transition state aromaticity.2 The authors discusses a variety of aromaticity measures (energetics, geometry, magnetic properties) that can be employed to analyze the nature of transition states, in addition to ground state molecules. This article provides a very clear description of the methods and a few examples. It is written for a more specialized audience than Houk’s article, but is nonetheless completely accessible to any chemist, even those with no computational background.


(1) Houk, K. N.; Liu, P. "Using Computational Chemistry to Understand & Discover Chemical Reactions," Daedalus 2014, 143, 49-66, DOI: 10.1162/DAED_a_00305.

(2) Schleyer, P. v. R.; Wu, J. I.; Cossio, F. P.; Fernandez, I. "Aromaticity in transition structures," Chem. Soc. Rev. 2014, 43, 4909-4921, DOI: 10.1039/C4CS00012A.

Houk &Schleyer Steven Bachrach 22 Dec 2014 No Comments

Structure of carbonic acid

I remain amazed at how regularly I read reports of structure determinations of what seem to be simple molecules, yet these structures have eluded determination for decades if not centuries. An example is the recently determined x-ray crystal structure of L-phenylalanine;1 who knew that growing these crystals would be so difficult?

The paper I want to discuss here is on the gas-phase structure of carbonic acid 1.2 Who would have thought that preparing a pure gas-phase sample would be so difficult? Schreiner and co-workers prepared carbonic acid by high-vacuum flash pyrolysis (HVFP) of di-tert-butyl carbonate, as shown in Scheme 1.

Scheme 1

Carbonic acid can appear in three difference conformations, shown in Figure 1. The two lowest energy conformations are separated by a barrier of 9.5 kcal mol-1 (estimated by focal point energy analysis). These conformations can be interconverted using near IR light. The third conformation is energetically inaccessible.






Figure 1. CCSD(T)/cc-pVQZ optimized structures of 1 (and the focal point relative energies in kcal mol-1) and the CCSD(T)/cc-pVTZ optimized structures of 2.

The structures of these two lowest energy conformations were confirmed by comparing their experimental IR spectra with the computed spectra (CCSD(T)/cc-pVTZ) and their experimental and computed rotational constants.

An interesting added component of this paper is that sublimation of the α- and β-polymorphs of carbonic acid do not produce the same compound. Sublimation of the β-isomorph does produce 1, but sublimation of the α-isomorph produces the methylester of 1, compound 2 (see Figure 1). The structure of 2 is again confirmed by comparison of the experimental and computed IR spectra.


(1) Ihlefeldt, F. S.; Pettersen, F. B.; von Bonin, A.; Zawadzka, M.; Görbitz, C. H. "The Polymorphs of L-Phenylalanine," Angew. Chem. Int. Ed. 2014, 53, 13600–13604, DOI: 10.1002/anie.201406886.

(2) Reisenauer, H. P.; Wagner, J. P.; Schreiner, P. R. "Gas-Phase Preparation of Carbonic Acid and Its Monomethyl Ester," Angew. Chem. Int. Ed. 2014, 53, 11766-11771, DOI: 10.1002/anie.201406969.>


1: InChI=1S/CH2O3/c2-1(3)4/h(H2,2,3,4)

2: InChI=1S/C2H4O3/c1-5-2(3)4/h1H3,(H,3,4)

Schreiner Steven Bachrach 09 Dec 2014 No Comments

Paul Schleyer: In Memorium

Professor Paul von Ragué Schleyer passed away November 21, 2014. Paul was a major force in physical organic and computational organic chemistry. I followed his career closely for the entirety of my own career; my doctoral studies with Andrew Streitwieser involved the analysis of the nature of the C-Li bond and we were in constant communication with Schleyer. Paul’s work on aromaticity greatly informed my thinking and my studies in this area.

I interviewed Paul in his office at the University of Georgia for the first edition of my book Computational Organic Chemistry. This interview was reprinted in the second edition without any changes. In honor of Paul, I am posting this interview here, so that our community can remember this important, inspirational figure.



Interview: Professor Paul von Ragué Schleyer

Interviewed March 28, 2006

Professor Paul Schleyer is the Graham Perdue Professor of Chemistry at the University of Georgia, where he has been for the past 8 years. Prior to that, he was a professor at the University at Erlangen (co-director of the Organic Institute) and the founding director of its Computer Chemistry Center. Schleyer began his academic career at Princeton University.

Professor Schleyer’s involvement in computational chemistry dates back to the 1960s, when his group was performing MM and semi-empirical computations as an adjunct to his predominantly experimental research program. This situation dramatically changed when Professor John Pople invited Schleyer to visit Carnegie-Mellon University in 1969 as the NSF Center of Excellence Lecturer. From discussions with Dr. Pople, it became clear to Schleyer that “ab initio methods could look at controversial subjects like the nonclassical carbocations. I became hooked on it!” The collaboration between Pople and Schleyer that originated from that visit lasted well over 20 years, and covered such topics as substituent effects, unusual structures that Schleyer terms “rule-breaking”, and organolithium chemistry. This collaboration started while Schleyer was at Princeton but continued after his move to Erlangen, where Pople came to visit many times. The collaboration was certainly of peers. “It would be unfair to say that the ideas came from me, but it’s clear that the projects we worked on would not have been chosen by Pople. Pople added a great deal of insight and he would advise me on what was computationally possible,” Schleyer recalls of this fruitful relationship.

Schleyer quickly became enamored with the power of ab initio computations to tackle interesting organic problems. His enthusiasm for computational chemistry eventually led to his decision to move to Erlangen – they offered unlimited (24/7) computer time, while Princeton’s counteroffer was just 2 hours of computer time per week. He left Erlangen in 1998 due to enforced retirement. However, his adjunct status at the University of Georgia allowed for a smooth transition back to the United States, where he now enjoys a very productive collaborative relationship with Professor Fritz Schaefer.

Perhaps the problem that best represents how Schleyer exploits the power of ab initio computational chemistry is the question of how to define and measure aromaticity. Schleyer’s interest in the concept of aromaticity spans his entire career. He was drawn to this problem because of the pervasive nature of aromaticity across organic chemistry. Schleyer describes his motivation: “Aromaticity is a central theme of organic chemistry. It is re-examined by each generation of chemists. Changing technology permits that re-examination to occur.” His direct involvement came about by Kutzelnigg’s development of a computer code to calculate chemical shifts. Schleyer began use of this program in the 1980s and applied it first to structural problems. His group “discovered in this manner many experimental structures that were incorrect.”

To assess aromaticity, Schleyer first computed the lithium chemical shifts in complexes formed between lithium cation and the hydrocarbon of interest. The lithium cation would typically reside above the aromatic ring and its chemical shift would be affected by the magnetic field of the ring. While this met with some success, Schleyer was frustrated by the fact that lithium was often not positioned especially near the ring, let alone in the center of the ring. This led to the development of nucleus-independent chemical shift (NICS), where the virtual chemical shift can be computed at any point in space. Schleyer advocated using the geometric center of the ring, then later a point 1 Å above the ring center.

Over time, Schleyer came to refine the use of NICS, advocating an examination of NICS values on a grid of points. His most recent paper posits using just the component of the chemical shift tensor perpendicular to the ring evaluated at the center of the ring. This evolution reflects Schleyer’s continuing pursuit of a simple measure of aromaticity. “Our endeavor from the beginning was to select one NICS point that we could say characterizes the compound,” Schleyer says. “The problem is that chemists want a number which they can associate with a phenomenon rather than a picture. The problem with NICS was that it was not soundly based conceptually from the beginning because cyclic electron delocalization-induced ring current was not expressed solely perpendicular to the ring. It’s only that component which is related to aromaticity.”

The majority of our discussion revolved around the definition of aromaticity. Schleyer argues that “aromaticity can be defined perfectly well. It is the manifestation of cyclic electron delocalization which is expressed in various ways. The problem with aromaticity comes in its quantitative definition. How big is the aromaticity of a particular molecule? We can answer this using some properties. One of my objectives is to see whether these various quantities are related to one another. That, I think, is still an open question.”

Schleyer further detailed this thought, “The difficulty in writing about aromaticity is that it is encrusted by two centuries of tradition, which you cannot avoid. You have to stress the interplay of the phenomena. Energetic properties are most important, but you need to keep in mind that aromaticity is only 5% of the total energy. But if you want to get as close to the phenomenon as possible, then one has to go to the property most closely related, which is magnetic properties.” This is why he focuses upon the use of NICS as an aromaticity measure. He is quite confident in his new NICS measure employing the perpendicular component of the chemical shift tensor. “This new criteria is very satisfactory,” he says. “Most people who propose alternative measures do not do the careful step of evaluating them against some basic standard. We evaluate against aromatic stabilization energies.”

Schleyer notes that his evaluation of the aromatic stabilization energy of benzene is larger than many other estimates. This results from the fact that, in his opinion, “all traditional equations for its determination use tainted molecules. Cyclohexene is tainted by hyperconjugation of about 10 kcal mol-1. Even cyclohexane is very tainted, in this case by 1,3-interactions.” An analogous complaint can be made about the methods Schleyer himself employs: NICS is evaluated at some arbitrary point or arbitrary set of points, the block-diagonalized “cyclohexatriene” molecule is a gedanken molecule. When pressed on what then to use as a reference that is not ‘tainted’, Schleyer made this trenchant comment: “What we are trying to measure is virtual. Aromaticity, like almost all concepts in organic chemistry, is virtual. They’re not measurable. You can’t measure atomic charges within a molecule. Hyperconjugation, electronegativity, everything is in this sort of virtual category. Chemists live in a virtual world. But science moves to higher degrees of refinement.” Despite its inherent ‘virtual’ nature, “Aromaticity has this 200 year history. Chemists are interested in the unusual stability and reactivity associated with aromatic molecules. The term survives, and remains an enormously fruitful area of research.”

His interest in the annulenes is a natural extension of the quest for understanding aromaticity. Schleyer was particularly drawn to [18]-annulene because it can express the same D6h symmetry as does benzene. His computed chemical shifts for the D6h structure differed significantly from the experimental values, indicating that the structure was clearly wrong. “It was an amazing computational exercise,” Schleyer mused, “because practically every level you used to optimize the geometry gave a different structure. MP2 overshot the aromaticity, HF and B3LYP undershot it. Empirically, we had to find a level that worked. This was not very intellectually satisfying but was a pragmatic solution.” Schleyer expected a lot of flak from crystallographers about this result, but in fact none occurred. He hopes that the x-ray structure will be re-done at some point.

Reflecting on the progress of computational chemistry, Schleyer recalls that “physical organic chemists were actually antagonistic toward computational chemistry at the beginning. One of my friends said that he thought I had gone mad. In addition, most theoreticians disdained me as a black-box user.” In those early years as a computational chemist, Schleyer felt disenfranchised from the physical organic chemistry community. Only slowly has he felt accepted back into this camp. “Physical organic chemists have adopted computational chemistry; perhaps, I hope to think, due to my example demonstrating what can be done. If you can show people that you can compute chemical properties, like chemical shifts to an accuracy that is useful, computed structures that are better than experiment, then they get the word sooner or later that maybe you’d better do some calculations.” In fact, Schleyer considers this to be his greatest contribution to science – demonstrating by his own example the importance of computational chemistry towards solving relevant chemical problems. He cites his role in helping to establish the Journal of Computational Chemistry in both giving name to the discipline and stature to its practitioners.

Schleyer looks to the future of computational chemistry residing in the breadth of the periodic table. “Computational work has concentrated on one element, namely carbon,” Schleyer says. “The rest of the periodic table is waiting to be explored.” On the other hand, he is dismayed by the state of research at universities. In his opinion, “the function of universities is to do pure research, not to do applied research. Pure research will not be carried out at any other location.” Schleyer sums up his position this way – “Pure research is like putting money in the bank. Applied research is taking the money out.” According to this motto, Schleyer’s account is very much in the black.

Reprinted from Computational Organic Chemistry, Steven M. Bachrach, 2014, Wiley:Hoboken.


Schleyer Steven Bachrach 02 Dec 2014 2 Comments

Dynamics in the Wittig reaction

If you hadn’t noticed, I am a big fan of the work that Dan Singleton is doing concerning the role of dynamics in discerning reaction mechanisms. Dan’s group has reported another outstanding study combining experiments, traditional QM computations, and molecular dynamics – this time on the Wittig reaction.1

The key question concerning the mechanism is whether a betaine intermediate is accessed along the reaction (path A) or whether the reaction proceeds in a concerted manner (path B). Earlier computations had supported the concerted pathway (B).

Experimental determination of the heavy atom kinetic isotope effect was made for Reaction 1.

Reaction 1

Using the 6-31+G(2df,p) basis set, three different density functionals predict three different potential energy surfaces. With M06-2x, the surface indicates path A (stepwise), with the first step rate-limiting. B3P86 also predicts the stepwise reaction, but the second step is rate-limiting. The Lc-wPBE functional predicts a concerted reaction. Using these surfaces, they predicted the carbon isotope effect and compared it to the experimental values. The best agreement is with the M06-2x surface with a weighting of the vibrational energies of the two different TSs. The optimized structures of the two transition states, the betaine intermediate, and the product are shown in Figure 1.





Figure 1. M06-2x/6-31+G(2df,p) optimized geometry of the critical points of Reaction 1.

The agreement of the predicted and experimental KIE is not ideal. So, they performed molecular dynamics computations with the ONIOM approach using M06-2x/6-31G* for Reaction 1 and 53 THF molecules treated at PM3. 360 trajectories were begun in the region of the first transition state (TS1), and they can be organized into 4 groups. The first group (128 trajectories) are reactions that produce product. The second group (76 cases) form the C-C bond but then it ruptures and returns to reactant. The third group (82 cases) have an immediate recrossing back to reactant, and the last group (16 cases) takes product back to the first TS and then returns to product. The predicted KIE using this weighted MD results gives values in outstanding agreement with the experiments.

Of the first group, about 50% pass from TS1 to TS2 in less than 150 fs, or in other words look like a concerted path. But a good number of trajectories reside in the betaine region for 1-2 ps.

In contrast, trajectories initiated from the betaine with equilibrated THF molecules indicate a median of 600 ps to travel from TS1 to TS2 and do not resemble a concerted path.

They argue that this bimodal distribution is in part associated with a solvent effect. When the first TS is crossed the solvent molecules are not equilibrated about the solute, and 10-20% of the trajectories immediately pass through the betaine region due to “dynamic matching” where the entering motion matches with exiting over the second transition state. The longer trajectories result from improper dynamic matching, but faster motion in the solute than motion amongst the solvent needed to stabilize the betaine. So, not only do we need to be concerned about dynamic effects involving the reactants, we need to be concerned about dynamics associated with the solvent too!


(1) Chen, Z.; Nieves-Quinones, Y.; Waas, J. R.; Singleton, D. A. "Isotope Effects, Dynamic Matching, and Solvent Dynamics in a Wittig Reaction. Betaines as Bypassed Intermediates," J. Am. Chem. Soc. 2014, 136, 13122-13125, DOI: 10.1021/ja506497b.

Singleton &Wittig Steven Bachrach 18 Nov 2014 No Comments

The unusual PES of (CO)3

As recently explicated by Wang and Borden using NIPE spectroscopy and computations, the potential energy surface of cyclopropyl-1,2,3-trione 1 is remarkably complex.1 (U)CCSD(T)//aug-cc-pVTZ computations of the D3h singlet (the 1A1’ state shown in Figure 1) is actually a hilltop, possessing two imaginary frequencies. Distorting the structure as indicated by these imaginary frequencies and then optimizing the structure leads directly to dissociation to three CO molecules. Thus, (CO)3 does not exist as a stable minima on the singlet surface.

The D3h triplet (the 3E” state shown in Figure 1) is not a critical point on the surface; due to the Jahn-Teller effect is distorts into two different states: the 3B1 state which is a local energy minimum, and the 3A2 state which is a transition state between the symmetry-related 3B1 states.

So, this implies the possibility of a very interesting NIPE experiment. If the radical anion (CO)3-.
loses an electron and goes to the singlet surface, it lands at a hilltop(!) and should have a very short lifetime. If it goes to the triplet surface, it lands at either a transition state (3A2) and again should have a short lifetime, or it can land at the 3B1 state and perhaps have some lifetime before it dissociates by losing one CO molecule.






Figure 1. (U)CCSD(T)//aug-cc-pVTZ optimized geometries of 1 and its radical anion.

The NIPE spectrum identifies three transitions. By comparing the energies of the electron loss seen in the experiment with the computations, along with calculating the Franck-Condon factors using the computed geometries and vibrational frequencies, the lowest energy transition is to the 1A1’ state, and the second transition is part of the vibrational progression also to the 1A1’ state. This is the first identification of vibrational frequencies associated with a hilltop structure. The third transition is to the 3A2 state. No transition to the 3B1 state is found due to the large geometric difference between the radical anion and the 3B1 state; the Franck-Condon factors are zero due to no overlap of their wavefunctions.

Once again, the power of the symbiotic relationship between experiment and computation is amply demonstrated in this paper.


(1) Chen, B.; Hrovat, D. A.; West, R.; Deng, S. H. M.; Wang, X.-B.; Borden, W. T. "The Negative Ion Photoelectron Spectrum of Cyclopropane-1,2,3-Trione Radical Anion, (CO)3•– — A Joint Experimental and Computational Study," J. Am. Chem. Soc. 2014, 136, 12345-12354, DOI: 10.1021/ja505582k.


1: InChI=1S/C3O3/c4-1-2(5)3(1)6

Borden Steven Bachrach 21 Oct 2014 No Comments

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