Archive for the 'Authors' Category

MD studies of simple pericyclic reactions

At the recent ACS meeting in New Orleans, Ken Houk spoke at the Dreyfus award session in honor of Michele Parrinello. Ken’s talk included discussion of some recent molecular dynamics studies of pericyclic reactions. Because of their similarities in approaches and observations, I will discuss three recent papers from his group (which Ken discussed in New Orleans) in this post.

The Cope rearrangement, a fundamental organic reaction, has been studied extensively by computational means (see Chapter 4.2 of my book). Mackey, Yang, and Houk examine the degenerate Cope rearrangement of 1,5-hexadiene with molecular dynamics at the (U)B3LYP/6-31G(d) level.1 They examined 230 trajectories, and find that of the 95% of them that are reactive, 94% are trajectories that directly cross through the transition zone. By this, Houk means that the time gap between the breaking and forming C-C bonds is less than 60 fs, the time for one C-C bond vibration. The average time in the transition zone is 35 fs. This can be thought of as “dynamically concerted”. For the other few trajectories, a transient diradical with lifetime of about 100 fs is found.

The dimerization of cyclopentadiene finds the two [4+2] pathways merging into a single bispericylic transition state. 2 Only a small minority (13%) of the trajectories sample the region about the Cope rearrangement that interconverts the two mirror image dimers. These trajectories average about 60 fs in this space, which comes from the time separation between the formation of the two new C-C bonds. The majority of the trajectories quickly pass through the dimerization transition zone in about 18 fs, and avoid the Cope TS region entirely. These paths can be thought of as “dynamically concerted”, while the other set of trajectories are “dynamically stepwise”. It should be noted however that the value of S2 in the Cope transition zone are zero and so no radicals are being formed.

Finally, Yang, Dong, Yu, Yu, Li, Jamieson, and Houk examined 15 different reactions that involve ambimodal (i.e. bispericyclic) transition states.3 They find a strong correlation between the differences in the bond lengths of the two possible new bond vs. their product distribution. So for example, in the reaction shown in Scheme 1, bond a is the one farthest along to forming. Bond b is slightly shorter than bond c. Which of these two is formed next is dependent on the dynamics, and it turns out the Pab is formed from 73% of the trajectories while Pac is formed only 23% of the time. This trend is seen across the 15 reaction, namely the shorter of bond b or c in the transition state leads to the larger product formation. When competing reactions involve bonds with differing elements, then a correlation can be found with bond order instead of with bond length.

Scheme 1

References

1) Mackey, J. L.; Yang, Z.; Houk, K. N., "Dynamically concerted and stepwise trajectories of the Cope rearrangement of 1,5-hexadiene." Chem. Phys. Lett. 2017, 683, 253-257, DOI: 10.1016/j.cplett.2017.03.011.

2) Yang, Z.; Zou, L.; Yu, Y.; Liu, F.; Dong, X.; Houk, K. N., "Molecular dynamics of the two-stage mechanism of cyclopentadiene dimerization: concerted or stepwise?" Chem. Phys. 2018, in press, DOI: 10.1016/j.chemphys.2018.02.020.

3) Yang, Z.; Dong, X.; Yu, Y.; Yu, P.; Li, Y.; Jamieson, C.; Houk, K. N., "Relationships between Product Ratios in Ambimodal Pericyclic Reactions and Bond Lengths in Transition Structures." J. Am. Chem. Soc. 2018, 140, 3061-3067, DOI: 10.1021/jacs.7b13562.

Cope Rearrangement &Diels-Alder &Dynamics &Houk Steven Bachrach 07 May 2018 No Comments

C60 Fullerene isomers

The Grimme group has examined all 1812 C60 isomers, in part to benchmark some computational methods.1 They computed all of these structures at PW6B95-D3/def2-QZVP//PBE-D3/def2-TZVP. The lowest energy structure is the expected fullerene 1 and the highest energy structure is the nanorod 2 (see Figure 1).


1


2

Figure 1. Optimized structures of the lowest (1) and highest (2) energy C60 isomers.

About 70% of the isomers like in the range of 150-250 kcal mol-1 above the fullerene 1, and the highest energy isomer 2 lies 549.1 kcal mol-1 above 1. To benchmark some computational methods, they selected the five lowest energy isomers and five other isomers with higher energy to serve as a new database (C60ISO), with energies computed at DLPNO-CCSD(T)/CBS*. The mean absolute deviation of the PBE-D3/def2-TZVP relative energies with the DLPNO-CCSD(T)/CBS* energies is relative large 10.7 kcal mol-1. However, the PW6B95-D3/def2-QZVP//PBE-D3/def2-TZVP method is considerably better, with a MAD of only 1.7 kcal mol-1. This is clearly a reasonable compromise method for fullerene-like systems, balancing accuracy with computational time.

They also compared the relative energies of all 1812 isomers computed at PW6B95-D3/def2-QZVP//PBE-D3/def2-TZVP with a number of semi-empirical methods. The best results are with the DFTB-D3 method, with an MAD of 5.3 kcal mol-1.

References

1) Sure, R.; Hansen, A.; Schwerdtfeger, P.; Grimme, S., "Comprehensive theoretical study of all 1812 C60 isomers." Phys. Chem. Chem. Phys. 2017, 19, 14296-14305, DOI: 10.1039/C7CP00735C.

InChIs

1: InChI=1S/C60/c1-2-5-6-3(1)8-12-10-4(1)9-11-7(2)17-21-13(5)23-24-14(6)22-18(8)28-20(12)30-26-16(10)15(9)25-29-19(11)27(17)37-41-31(21)33(23)43-44-34(24)32(22)42-38(28)48-40(30)46-36(26)35(25)45-39(29)47(37)55-49(41)51(43)57-52(44)50(42)56(48)59-54(46)53(45)58(55)60(57)59
InChIKey=XMWRBQBLMFGWIX-UHFFFAOYSA-N

2: InChI=1S/C60/c1-11-12-2-21(1)31-41-32-22(1)3-13(11)15-5-24(3)34-43(32)53-55-47-36-26-6-16-17-7(26)28-9-19(17)20-10-29-8(18(16)20)27(6)37-46(36)54(51(41)55)52-42(31)33-23(2)4(14(12)15)25(5)35-44(33)58-56(52)48(37)39(29)50-40(30(9)10)49(38(28)47)57(53)59(45(34)35)60(50)58
InChIKey=AGZHNPDQKMDYHI-UHFFFAOYSA-N

fullerene &Grimme Steven Bachrach 05 Mar 2018 No Comments

New Procedure for computing NMR spectra with spin-spin coupling

Computed NMR spectra have become a very useful tool in identifying chemical structures. I have blogged on this multiple times. A recent trend has been the development of computational procedures that lead to computed spectra (again, see that above link). Now, Grimme, Neese and coworkers have offered their approach to computed NMR spectra, including spin-spin splitting.1

Their procedure involves four distinct steps.

  1. Generation of the conformer and rotamer space. This is a critical distinctive element of their method in that they take a number of different tacks for sampling conformational space to insure that they have identified all low-energy structures. This involves a combination of normal mode following, genetic structure crossing (based on genetic algorithms for optimization), and molecular dynamics. Making this all work is their choice of using the computational efficient GFN-xTB2 quantum mechanical method.
  2. The low-energy structures are then subjected to re-optimization at PBEh-3c and then single-point energies obtained at DSD-BLYP-D3/def2-TZVPP including treatment of solvation by COSMO-RS. The low-energy structures that contribute 4% or more of the Boltzmann-weighted population are then carried forward.
  3. Chemical shifts and spin-spin coupling constants are then computed with the PBE0 method and the pcS and pcJ basis sets developed by Jensen for computing NMR shifts.3
  4. Lastly, the chemical shifts and coupling constants are averaged and the spin Hamiltonian is solved.

The paper provides a number of examples of the application of the methodology, all with quite good success. The computer codes to run this method are available for academic use from xtb@thch.uni-bonn.de.

References

1) Grimme, S.; Bannwarth, C.; Dohm, S.; Hansen, A.; Pisarek, J.; Pracht, P.; Seibert, J.; Neese, F., "Fully Automated Quantum-Chemistry-Based Computation of Spin–Spin-Coupled Nuclear Magnetic Resonance Spectra." Angew. Chem. Int. Ed. 2017, 56, 14763-14769, DOI: 10.1002/anie.201708266.

2) Grimme, S.; Bannwarth, C.; Shushkov, P., "A Robust and Accurate Tight-Binding Quantum Chemical Method for Structures, Vibrational Frequencies, and Noncovalent Interactions of Large Molecular Systems Parametrized for All spd-Block Elements (Z = 1–86)." J. Chem. Theory Comput. 2017, 13, 1989-2009, DOI: 10.1021/acs.jctc.7b00118.

3) Jensen, F., "Basis Set Convergence of Nuclear Magnetic Shielding Constants Calculated by Density Functional Methods." J. Chem. Theory Comput. 2008, 4, 719-727, DOI: 10.1021/ct800013z.

Grimme &NMR Steven Bachrach 05 Feb 2018 No Comments

Isotope Controlled Selectivity

I seem to be recently flooded with papers dealing with tunneling in organic systems. Well, here’s one more! Kozuch, Borden, Schreiner and co-workers seek out systems whereby isotopic substitution might lead to reaction selectivity.1 Their base system is cyclopropylmethylcarbene 1, which can undergo three different reactions: (a) the ring can expand to give 1-methylcyclobut-1-ene 2, (b) a hydrogen can shift from the terminal methyl group to give vinylcyclopropane 3, or (c) the methane hydrogen can shift to produce ethylidenecyclopropane 4. This last option can be neglected since its barrier (20.5 kcal mol-1) is so much higher than for the other two, 7.5 kcal mol-1 for the ring expansion and 12.1 kcal mol-1 for the [1,2]H-shift converting 13.

At high temperature, the ring expansion to 2 will dominate, but at low temperature the hydrogen shift to 3 might dominate by tunneling through the barrier due to the low mass and short distances involved. The reaction rates were computed using B3LYP/6-31G(d,p) and small-curvature tunneling. At low temperature, the rate for the hydrogen shift is 10 orders of magnitude faster than the ring expansion. Thinking that deuterium substitution of the terminal methyl group might slow down the rate of the [1,2]-shift, they computed the rates for the reactions of 1-d3, and in fact the rate of this shift does reduce by 104 but it is still much faster than the rate for ring expansion. What is needed is a system where the rate for ring expansion is slower than the rate for hydrogen migration but faster than the rate of deuterium migration.

They examine a number of different substituents that may help to lower the barrier for the ring expansion. The methoxy derivative 5 turns out to suit the bill perfectly. The methoxy group reduces the barrier for ring expansion from 7.5 kcal mol-1 with 1 to 2.5 kcal mol-1 with 5. With hydrogenated 5, the [1,2]H-shift is 103 times faster than ring expansion, but with deuterated 5, ring expansion is twice as fast as the deuterium migration.

The authors call this isotope controlled selectivity (ICS), and this is the first example of this type of control.

References

1. Nandi, A.; Gerbig, D.; Schreiner, P. R.; Borden, W. T.; Kozuch, S., Isotope-Controlled Selectivity by Quantum Tunneling: Hydrogen Migration versus Ring Expansion in Cyclopropylmethylcarbenes. J. Am. Chem. Soc. 2017, 139, 9097-9099, DOI: 10.1021/jacs.7b04593.

InChIs

1: InChI=1S/C5H8/c1-2-5-3-4-5/h5H,3-4H2,1H3
InChIKey=KJIJNBZLGHBOTI-UHFFFAOYSA-N

2: InChI<=1S/C5H8/c1-5-3-2-4-5/h3H,2,4H2,1H3
InChIKey=AVPHQXWAMGTQPF-UHFFFAOYSA-N

3: InChI=1S/C5H8/c1-2-5-3-4-5/h2,5H,1,3-4H2
InChIKey=YIWFBNMYFYINAD-UHFFFAOYSA-N

4: InChI=1S/C5H8/c1-2-5-3-4-5/h2H,3-4H2,1H3
InChIKey=ZIFNDRXSSPCNID-UHFFFAOYSA-N

5: InChI=1S/C6H10O/c1-3-6(7-2)4-5-6/h4-5H2,1-2H3
InChIKey=YMBSTCICUAORNN-UHFFFAOYSA-N

6: InChI<=1S/C6H10O/c1-5-3-4-6(5)7-2/h3-4H2,1-2H3
InChIKey=QBLNAZHAVPMLHB-UHFFFAOYSA-N

7: InChI<=1S/C6H10O/c1-3-6(7-2)4-5-6/h3H,1,4-5H2,2H3
InChIKey=FHYLDABSPVPDTJ-UHFFFAOYSA-N

Borden &Isotope Effects &Schreiner &Tunneling Steven Bachrach 22 Jan 2018 No Comments

Perspective on Tunneling Control

Over the past nine years the Schreiner group, often in collaboration with the Allen group, have produced some remarkable studies demonstrating the role of tunneling control. (I have made quite a number of posts on this topics.) Tunneling control is a third mechanism for dictating product formation, in tandem with kinetic control (the favored product is the one that results from the lowest barrier) and thermodynamic control (the favored product is the one that has the lowest energy). Tunneling control has the favored product resulting from the narrowest mass-considered barrier.

Schreiner has written a very clear perspective on tunneling control. It is framed quite interestingly by some fascinating quotes:

It is probably fair to say that many organic chemists view the concept of tunneling, even of hydrogen atoms, with some skepticism. – Carpenter 19832

Reaction processes have been considered as taking place according to the laws of classical mechanics, quantum mechanical theory being only employed in calculating interatomic forces. – Bell 19333

Schreiner’s article makes it very clear how critical it is to really think about reactions from a truly quantum mechanical perspective. He notes the predominance of potential energy diagrams that focus exclusively on the relative energies and omits any serious consideration of the reaction coordinate metrics, like barrier width. When one also considers the rise in our understanding of the role of reaction dynamics in organic chemistry (see, for example, these many posts), just how long will it take for these critical notions to penetrate into standard organic chemical thinking? As Schreiner puts it:

It should begin by including quantum phenomena in introductory textbooks, where they are, at least in organic chemistry, blatantly absent. To put this oversight in words similar to those used much earlier by Frank Weinhold in a different context: “When will chemistry textbooks begin to serve as aids, rather than barriers, to this enriched quantum-mechanical perspective?”4

References

1) Schreiner, P. R., "Tunneling Control of Chemical Reactions: The Third Reactivity Paradigm." J. Am. Chem. Soc. 2017, 139, 15276-15283, DOI: 10.1021/jacs.7b06035.

2) Carpenter, B. K., "Heavy-atom tunneling as the dominant pathway in a solution-phase reaction? Bond shift in antiaromatic annulenes." J. Am. Chem. Soc. 1983, 105, 1700-1701, DOI: 10.1021/ja00344a073.

3) Bell, R. P., "The Application of Quantum Mechanics to Chemical Kinetics." Proc. R. Soc. London, Ser. A 1933, 139 (838), 466-474, DOI: 10.1098/rspa.1933.0031.

4) Weinhold, F., "Chemistry: A new twist on molecular shape." Nature 2001, 411, 539-541, DOI: 10.1038/35079225.

Schreiner &Tunneling Steven Bachrach 13 Nov 2017 No Comments

Heavy atom tunneling in semibullvalene

Another prediction made by quantum chemistry has now been confirmed. In 2010, Zhang, Hrovat, and Borden predicted that the degenerate rearrangement of semibullvalene 1 occurs with heavy atom tunneling.1 For example, the computed rate of the rearrangement including tunneling correction is 1.43 x 10-3 s-1 at 40 K, and this rate does not change with decreasing temperature. The predicted half-life of 485 s is 1010 shorter than that predicted by transition state theory.

Now a group led by Sander has examined the rearrangement of deuterated 2.2 The room temperature equilibrium mixture of d42 and d22 was deposited at 3 K. IR observation showed a decrease in signal intensities associated with d42 and concomitant growth of signals associated with d22. The barrier for this interconversion is about 5 kcal mol-1, too large to be crossed at this temperature. Instead, the interconversion is happening by tunneling through the barrier (with a rate about 10-4 s-1), forming the more stable isomer d22 preferentially. This is exactly as predicted by theory!

References

1. Zhang, X.; Hrovat, D. A.; Borden, W. T., "Calculations Predict That Carbon Tunneling Allows the Degenerate Cope Rearrangement of Semibullvalene to Occur Rapidly at Cryogenic Temperatures." Org. Letters 2010, 12, 2798-2801, DOI: 10.1021/ol100879t.

2. Schleif, T.; Mieres-Perez, J.; Henkel, S.; Ertelt, M.; Borden, W. T.; Sander, W., "The Cope Rearrangement of 1,5-Dimethylsemibullvalene-2(4)-d1: Experimental Evidence for Heavy-Atom Tunneling." Angew. Chem. Int. Ed. 2017, 56, 10746-10749, DOI: 10.1002/anie.201704787.

InChIs

1: InChI=1S/C8H8/c1-3-6-7-4-2-5(1)8(6)7/h1-8H
InChIKey=VEAPRCKNPMGWCP-UHFFFAOYSA-N

d42: InChI=1S/C10H12/c1-9-5-3-7-8(4-6-9)10(7,9)2/h3-8H,1-2H3/i5D
InChIKey=WUJOLJNLXLACNA-UICOGKGYSA-N

d22: InChI=1S/C10H12/c1-9-5-3-7-8(4-6-9)10(7,9)2/h3-8H,1-2H3/i7D
InChIKey=WUJOLJNLXLACNA-WHRKIXHSSA-N

Borden &Tunneling Steven Bachrach 02 Nov 2017 No Comments

Review of the Activation Strain/Distortion-Interaction Model

Bickelhaupt and Houk present a nice review of their separately developed, but conceptually identical model for assessing reactivity.1 Houk termed this the “distortion/interaction” model,2 while Bickelhaupt named it “activation strain”.3 The concept is that the activation barrier can be dissected in a distortion or stain energy associated with bringing the reactants into the geometry of the transition state, and the interaction energy is the stabilization energy afforded by the molecular orbital interactions of the reactant components with each other in the transition state.

The review discusses a broad range of applications, including SN2 and E2 reactions, pericyclic reactions (including Diels-Alder reactions of enones and the dehdydro Diels-Alder reaction that I have discussed in this blog), a click reaction, a few examples involving catalysis, and the regioselectivity of indolyne (see this post). They also discuss the role of solvent and the relationship of this model to Marcus Theory.

I also want to mention in passing a somewhat related article by Jorgensen and co-authors published in the same issue of Angewandte Chemie as the above review.4 This article discusses the paucity of 10 electron cycloaddition reactions, especially in comparison to the large number of very important cycloaddition reactions involving 6 electrons, such as the Diels-Alder reaction, the Cope rearrangement, and the Claisen rearrangement. While the article does not focus on computational methods, computations have been widely used to discuss 10-electron cycloadditions. The real tie between this paper and the review discussed above is Ken Houk, whose graduate career started with an attempt to perform a [6+4] cycloaddition, and he has revisited the topic multiple times throughout his career.

References

1. Bickelhaupt, F. M.; Houk, K. N., "Analyzing Reaction Rates with the Distortion/Interaction-Activation Strain Model." Angew. Chem. Int. Ed. 2017, 56, 10070-10086, DOI: 10.1002/anie.201701486.

2. Ess, D. H.; Houk, K. N., "Distortion/Interaction Energy Control of 1,3-Dipolar Cycloaddition Reactivity." J. Am. Chem. Soc. 2007, 129, 10646-10647, DOI: 10.1021/ja0734086

3. Bickelhaupt, F. M., "Understanding reactivity with Kohn-Sham molecular orbital theory: E2-SN2 mechanistic spectrum and other concepts." J. Comput. Chem. 1999, 20, 114-128

4. Palazzo, T. A.; Mose, R.; Jørgensen, K. A., "Cycloaddition Reactions: Why Is It So
Challenging To Move from Six to Ten Electrons?" Angew. Chem. Int. Ed. 2017, 56, 10033-10038, DOI: 10.1002/anie.201701085.

Houk Steven Bachrach 16 Oct 2017 No Comments

Bispericyclic reaction involving two [6+4] cycloadditions

Bispericyclic transition states arise when two pericyclic reactions merge to a common transition state. This leads to a potential energy surface with a bifurcation such that reactions that traverse this type of transition state will head towards two different products. The classic example is the dimerization of cyclopentadiene, involving two [4+2] Diels-Alder reactions. Unusual PESs are discussed in my book and in past blog posts.

Houk and coworkers have now identified a bispericyclic transition state involving two [6+4] cycloadditions.1 Reaching back to work Houk pursued as a graduate student with Woodward for inspiration, these authors examined the reaction of tropone 1 with dimethylfulvene 2. Each moiety can act as the diene or triene component of a [6+4] allowed cycloaddition:

The product with fulvene 2 as the 6 π-e component and tropone as the 4 π-e component [6F+4T] is 3, while reversing their participation in the [6T+4F] cycloaddition leads to 4. A variety of [4+2] reactions are also possible. All of these reactions were investigated at PCM/M06-2X/6-311+G(d,p)//B3LYP-D3/6-31G(d). The reaction leading to 3 is exothermic by 3.0 kcal mol-1, while the reaction to 4 endothermic by 1.3 kcal mol-1.

Interestingly, there is only one transition state that leads to both 3 and 4, the first known bispericyclic transition state for two conjoined [6+4] cycloadditions. The barrier is 27.9 kcal mol-1. The structures of the two products and the transition state leading to them are shown in Figure 1. 3 and 4 can interconvert through a Cope transition state, also shown in Figure 1, with a barrier of 26.3 kcal mol-1 (for 43).

3

4

TS [6+4]

TS Cope

Figure 1. B3LYP-D3/6-31G(d) optimized geometries.

Given that a single transition leads to two products, the product distribution is dependent on the molecular dynamics. A molecular dynamics simulation at B3LYP-D3/6-31G(d) with 117 trajectories indicates that 4 is formed 91% while 3 is formed only 9%. Once again, we are faced with the reality of much more complex reaction mechanisms/processes than simple models would suggest.

References

1) Yu, P.; Chen, T. Q.; Yang, Z.; He, C. Q.; Patel, A.; Lam, Y.-h.; Liu, C.-Y.; Houk, K. N., "Mechanisms and Origins of Periselectivity of the Ambimodal [6 + 4] Cycloadditions of Tropone to Dimethylfulvene." J. Am. Chem. Soc. 2017, 139 (24), 8251-8258, DOI: 10.1021/jacs.7b02966.

InChIs

1: InChI=1S/C7H6O/c8-7-5-3-1-2-4-6-7/h1-6H
InChIKey=QVWDCTQRORVHHT-UHFFFAOYSA-N

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

3:InChI=1S/C15H16O/c1-15(2)10-6-8-12(14(16)9-7-10)11-4-3-5-13(11)15/h3-12H,1-2H3
InChIKey=SEKRUGIZAIQCDA-UHFFFAOYSA-N

4: InChI=1S/C15H16O/c1-9(2)14-10-7-8-11(14)13-6-4-3-5-12(10)15(13)16/h3-8,10-13H,1-2H3
InChIKey=AQQAMUGJSGJKLC-UHFFFAOYSA-N

cycloadditions &Dynamics &Houk Steven Bachrach 07 Aug 2017 No Comments

A few review articles

A few nice review/opinion pieces have been piling up in my folder of papers of interest for this Blog. So, this post provides a short summary of a number of review articles that computationally-oriented chemists may find of interest.

Holy Grails in computational chemistry

Houk and Liu present a short list of “Holy Grails” in computationally chemistry.1 They begin by pointing out a few technical innovations that must occur for the Grails to be found: development of a universal density functional; an accurate, generic force field; improved sampling for MD; and dealing with the combinatorial explosion with regards to conformations and configurations. Their list of Grails includes predicting crystal structures and structure of amorphous materials, catalyst design, reaction design, and device design. These Grails overlap with the challenges I laid out in my similarly-themed article in 2014.2

Post-transition state bifurcations and dynamics

Hare and Tantillo review the current understanding of post-transition state bifurcations (PTSB).3 This type of potential energy surface has been the subject of much of Chapter 8 of my book and many of my blog posts. What is becoming clear is the possibility of a transition state followed by a valley-ridge inflection leads to reaction dynamics where trajectories cross a single transition state but lead to two different products. This new review updates the state-of-the-art from Houk’s review4 of 2008 (see this post). Mentioned are a number of studies that I have included in this Blog, along with reactions involving metals, and biochemical systems (many of these examples come from the Tantillo lab). They close with the hope that their review might “inspire future studies aimed at controlling selectivity for reactions with PTSBs” (italics theirs). I might offer that controlling selectivity in these types of dynamical systems is another chemical Grail!

The Hase group has a long review of direct dynamics simulations.5 They describe a number of important dynamics studies that provide important new insight to reaction mechanism, such as bimolecular SN2 reactions (including the roundabout mechanism) and unimolecular dissociation. They write a long section on post-transition state bifurcations, and other dynamic effects that cannot be interpreted using transition state theory or RRKM. This section is a nice complement to the Tantillo review.

Benchmarking quantum chemical methods

Mata and Suhm look at our process of benchmarking computational methods.6 They point out the growing use of high-level quantum computations as the reference for benchmarking new methods, often with no mention of any comparison to experiment. In defense of theoreticians, they do note the paucity of useful experimental data that may exist for making suitable comparisons. They detail a long list of better practices that both experimentalists and theoreticians can take to bolster both efforts, leading to stronger computational tools that are more robust at helping to understand and discriminate difficult experimental findings.

References

1) Houk, K. N.; Liu, F., "Holy Grails for Computational Organic Chemistry and Biochemistry." Acc. Chem. Res. 2017, 50 (3), 539-543, DOI: 10.1021/acs.accounts.6b00532.

2) Bachrach, S. M., "Challenges in computational organic chemistry." WIRES: Comput. Mol. Sci. 2014, 4, 482-487, DOI: 10.1002/wcms.1185.

3) Hare, S. R.; Tantillo, D. J., "Post-transition state bifurcations gain momentum – current state of the field." Pure Appl. Chem. 2017, 89, 679-698, DOI: 0.1515/pac-2017-0104.

4) Ess, D. H.; Wheeler, S. E.; Iafe, R. G.; Xu, L.; Çelebi-Ölçüm, N.; Houk, K. N., "Bifurcations on Potential Energy Surfaces of Organic Reactions." Angew. Chem. Int. Ed. 2008, 47, 7592-7601, DOI: 10.1002/anie.200800918

5) Pratihar, S.; Ma, X.; Homayoon, Z.; Barnes, G. L.; Hase, W. L., "Direct Chemical Dynamics Simulations." J. Am. Chem. Soc. 2017, 139, 3570-3590, DOI: 10.1021/jacs.6b12017.

6) Mata, R. A.; Suhm, M. A., "Benchmarking Quantum Chemical Methods: Are We Heading in the Right Direction?" Angew. Chem. Int. Ed. 2017, ASAP, DOI: 10.1002/anie.201611308.

Dynamics &Houk Steven Bachrach 25 Jul 2017 No Comments

A record short H…H non-bonding interaction

Following on previous work (see these posts on ladderane and hexaphenylethane), Schreiner, Grimme and co-workers have examined the structure of the all-meta tri(di-t-butylphenyl)methane dimer 12.1 In the study of hexaphenylethane,2 Schreiner and Grimme note that t-butyl groups stabilize highly congested structures through dispersion, identifying them as “dispersion energy donors”.3 The idea here is that the dimer of 1 will be stabilized by these many t-butyl groups. In fact, the neutron diffraction study of the crystal structure of 12 shows an extremely close approach of the two methane hydrogens of only 1.566 Å, the record holder for the closest approach of two formally non-bonding hydrogen atoms.

To understand the nature of this dimeric structure, they employed a variety of computational techniques. (Shown in Figure 1 is the B3LYPD3ATM(BJ)/def2-TZVPP optimized geometry of 12.) The HSE-3c (a DFT composite method) optimized crystal structure predicts the HH distance is 1.555 Å. The computed gas phase structure lengthens the distance to 1.634 Å, indicating a small, but essential, role for packing forces. Energy decomposition analysis of 12 at B3LYP-D3ATM(BJ)/def2-TZVPP indicates a dominant role for dispersion in holding the dimer together. While 12 is bound by about 8 kcal mol-1, the analogue of 12 lacking all of the t-butyl groups (the dimer of triphenylmethane 22) is unbound by over 8 kcal mol-1. Topological electron density analysis does show a bond critical point between the two formally unbound hydrogen atoms, and the noncovalent interaction plot shows an attractive region between these two atoms.

Figure 1. ATM(BJ)/def2-TZVPP optimized geometry of 12, with most of the hydrogens suppressed for clarity. (Selecting the molecule will launch Jmol with the full structure, including the hydrogens.)

References

1) Rösel, S.; Quanz, H.; Logemann, C.; Becker, J.; Mossou, E.; Cañadillas-Delgado, L.; Caldeweyher, E.; Grimme, S.; Schreiner, P. R., "London Dispersion Enables the Shortest Intermolecular Hydrocarbon H···H Contact." J. Am. Chem. Soc. 2017, 139, 7428–7431, DOI: 10.1021/jacs.7b01879.

2) Grimme, S.; Schreiner, P. R., "Steric Crowding Can Stabilize a Labile Molecule: Solving the Hexaphenylethane Riddle." Angew. Chem. Int. Ed. 2011, 50 (52), 12639-12642, DOI: 10.1002/anie.201103615.

3) Grimme, S.; Huenerbein, R.; Ehrlich, S., "On the Importance of the Dispersion Energy for the Thermodynamic Stability of Molecules." ChemPhysChem 2011, 12 (7), 1258-1261, DOI: 10.1002/cphc.201100127.

InChIs

1: InChI=1S/C43H64/c1-38(2,3)31-19-28(20-32(25-31)39(4,5)6)37(29-21-33(40(7,8)9)26-34(22-29)41(10,11)12)30-23-35(42(13,14)15)27-36(24-30)43(16,17)18/h19-27,37H,1-18H3
InChIKey=VFNQDWKFTWSJAU-UHFFFAOYSA-N

Grimme &Schreiner Steven Bachrach 21 Jun 2017 No Comments

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