Archive for the ‘pericyclic’ Category

Computationally directed synthesis: 2,3-dimethyl-2-butene + NO(+).

Saturday, September 6th, 2014
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In the previous posts, I explored reactions which can be flipped between two potential (stereochemical) outcomes. This triggered a memory from Alex, who pointed out this article from 1999[1] in which the nitrosonium cation as an electrophile can have two outcomes A or B when interacting with the electron-rich 2,3-dimethyl-2-butene. NO NMR evidence clearly pointed to the π-complex A as being formed, and not the cyclic nitrosonium species B (X=Al4). If you are wondering where you have seen an analogy for the latter, it would be the species formed when bromine reacts with an alkene (≡ Br+, X=Br or Br3). The two structures are shown below[1] tetramethyletylene-NO+ Since the topic that sparked this concerned pericyclic reactions, it seemed possible that if it had been formed, species B would immediately undergo a pericyclic electrocyclic reaction to form the rather odd-looking cation C, which might then be trapped by eg X(-) to form the nitrone D. So this post is an exploration of what happens when X-NO (X= CF3COO, trifluoracetate) interacts with 2,3-dimethyl-2-butene, as an illustration of what can be achieved nowadays from about 2 days worth of dry-lab computation as a prelude to e.g. an experiment in the wet-lab (it would take a little more than two days to achieve the latter I suspect). Hence computationally directed synthesis. The model is set up as ωB97XD/6-311G(d,p)/SCRF=chloroform. A transition state is located[2] and the resulting IRC (below) [3] does not quite have the outcome the above scheme would suggest. NOa NOe NOg Neither A nor B is formed; instead it is the tetrahedral species E, which is ~15 kcal/mol endothermic. NOaa I should immediately point out that this is not inconsistent with the formation of A as previously characterised[1]. That is because this experiment was conducted with a non-nucleophilic counter-anion (X=Al4), whereas in the computational simulation above, we have a nucleophilic anion (X= CF3CO2). What a difference the inclusion of a counter-ion in the calculation can have! The barrier however (~35 kcal/mol) is a little too high for a facile thermal reaction. In the second of this two-stage reaction, E now ring-opens to form the anticipated D[4] with quite a small barrier of ~6 kcal/mol, but a highly exothermic outcome. I ask this question about it; can this still be described as a pericyclic process? (there is some analogy to the electrocyclic ring opening of a cyclopropyl tosylate). NObNObe So what are the conclusions? Well, because of the rather high initial barrier, the alkene will need activation (by electron donating substituents, perhaps OMe) for the reaction to become more viable. But if it works, it could be an interesting synthesis of nitrones (I have not yet searched to find out if the reaction is actually known).

References

  1. G.I. Borodkin, I.R. Elanov, A.M. Genaev, M.M. Shakirov, and V.G. Shubin, "Interaction in olefin–NO+ complexes: structure and dynamics of the NO+–2,3-dimethyl-2-butene complex", Mendeleev Communications, vol. 9, pp. 83-84, 1999. http://dx.doi.org/10.1070/MC1999v009n02ABEH000995
  2. Henry S Rzepa., "C8H12F3NO3", 2014. http://dx.doi.org/10.14469/ch/24979
  3. Henry S. Rzepa., "Gaussian Job Archive for C8H12F3NO3", 2014. http://dx.doi.org/10.6084/m9.figshare.1162797
  4. Henry S. Rzepa., "Gaussian Job Archive for C8H12F3NO3", 2014. http://dx.doi.org/10.6084/m9.figshare.1162676

Full circle. Stereoisomeric transition states for [1,4] pericyclic shifts.

Monday, August 18th, 2014
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This post, the fifth in the series, comes full circle. I started off by speculating how to invert the stereochemical outcome of an electrocyclic reaction by inverting a bond polarity. This led to finding transition states for BOTH outcomes with suitable substitution, and then seeking other examples. Migration in homotropylium cation was one such, with the “allowed/retention” transition state proving a (little) lower in activation energy than the “forbidden/inversion” path. Here, I show that with two electrons less, the stereochemical route indeed inverts.mob-inva First, a [1,4] alkyl shift with inversion at the migrating carbon (ωB97XD/6-311G(d,p)/SCRF=chloroform); as a four-electron process, this is the “allowed” route.[1] mob-inva The “forbidden” route corresponds to retention of configuration at the migrating carbon.[2] mob-retb The barriers for each process can be seen below from the IRCs. That for inversion is ~4.5 kcal/mol lower than retention. This nicely transposes the values for the six-electron homologue shown in the previous post. mob-invmob-ret There is one more nugget of insight that can be extracted. The start/end-point for the six-electron process (homotropylium cation) was, as the name implies, homoaromatic. Now, with a four-electron system we also have an inverse. Nominally, we should now end with homo-antiaromaticity (but see [3]). But antiaromaticity is avoided whenever possible, and so the homoaromatic bond observed in homotropylium is not formed. It resolutely remains a σ-bond (1.48Å) thus sequestering two electrons, and the remaining two electrons simply form a delocalised allyl cation. With the six-electron homotropylium, reactant/product were stabilised by that additional (homo)aromaticity, thus inducing a relatively high barrier. With the four-electron system here, no such reactant/product stabilisation occurs, and hence the reaction barriers are now significantly lower. A rather neat pedagogic example.

References

  1. Henry S. Rzepa., "Gaussian Job Archive for C8H11(1+)", 2014. http://dx.doi.org/10.6084/m9.figshare.1142175
  2. Henry S. Rzepa., "Gaussian Job Archive for C8H11(1+)", 2014. http://dx.doi.org/10.6084/m9.figshare.1142174
  3. C.S.M. Allan, and H.S. Rzepa, "Chiral Aromaticities. A Topological Exploration of Möbius Homoaromaticity", Journal of Chemical Theory and Computation, vol. 4, pp. 1841-1848, 2008. http://dx.doi.org/10.1021/ct8001915

An unusual [1,6] shift in homotropylium cation exhibiting zones of aromaticity.

Tuesday, August 12th, 2014
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One thing leads to another. Thus in the previous post, I described a thermal pericyclic reaction that appears to exhibit two transition states resulting in two different stereochemical outcomes. I noted that another such reaction appeared to be a [1,6] carousel migration in homotropylium cation,[1] where transition states for both retention and inversion of the configuration of the migrating group (respectively formally allowed and forbidden) were reported (scheme below). Here I explore this system further. homotropylium Firstly, the pathway leading to inversion.[2] The reaction path (ωB97XD/6-311G(d,p)/SCRF=chloroform) has got a very odd (table-top mountain) shape, whereby the region of the transition state (IRC = 0.0) is very flat, and the region close to reactant and (identical) product is very steep. The gradient norm shows this best, with sharp spikes at IRC ± 4.2. Something clearly is happening here to cause this behaviour. Before moving on to analyze this, I want you first to observe the methyl groups below. Note how one of them rotates at the start of the process, and the other at the end. I have elsewhere called this behaviour the methyl flag, and it is due to stereoelectronic re-alignments of the C-H groups accompanying the changes in the conjugated array. htropa htrop htropG The homotropylium cation is said to be homoaromatic, indicating that cyclic conjugation can be maintained across a ring in which the σ framework is interrupted at one point. A NICS probe placed at the ring critical point of this molecule reveals a chemical shift of -11.3 ppm[3], very similar to eg that obtained for benzene itself. The three highest doubly occupied NBOs (below) show two normal π-type orbitals and one rather different one that spans the homo-bond (the MOs, before you ask, are a bit of a mess, with lots of mixed contributions from other parts of the σ framework).

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References

  1. A.M. Genaev, G.E. Sal’nikov, and V.G. Shubin, "Energy barriers to carousel rearrangements of carbocations: Quantum-chemical calculations vs. experiment", Russian Journal of Organic Chemistry, vol. 43, pp. 1134-1138, 2007. http://dx.doi.org/10.1134/S1070428007080076
  2. Henry S. Rzepa., "Gaussian Job Archive for C10H13(1+)", 2014. http://dx.doi.org/10.6084/m9.figshare.1134556
  3. Henry S. Rzepa., "Gaussian Job Archive for C10H13(1+)", 2014. http://dx.doi.org/10.6084/m9.figshare.1135694

Using a polar bond to flip: on the knife-edge!

Sunday, August 10th, 2014
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In my first post on the topic, I discussed how inverting the polarity of the C-X bond from X=O to X=Be (scheme below) could flip the stereochemical course of the electrocyclic pericyclic reaction of a divinyl system. This was followed up by exploring what happens at the half way stage, i.e. X=CH2, the answer being that one gets an antarafacial pathway as with X=O. Here I fill in another gap, X=BH to see if a metaphorical microscope can be used to view the actual region of the “flip” to a suprafacial mode.divinylketon This time, uniquely, it proved possible to locate TWO transition states for this process, one suprafacial[1] and one antarafacial[2], this latter being 10.5 kcal/mol lower in ΔG (ωB97XD/6-311G(d,p)/SCRF=dichloromethane). It is quite rare to be able to find BOTH stereochemical outcomes of a thermal pericyclic reaction.

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References

  1. Henry S. Rzepa., "Gaussian Job Archive for C5H7B", 2014. http://dx.doi.org/10.6084/m9.figshare.1133933
  2. Henry S. Rzepa., "Gaussian Job Archive for C5H7B", 2014. http://dx.doi.org/10.6084/m9.figshare.1133934

Using a polar bond to flip: a follow up project.

Wednesday, August 6th, 2014
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In my earlier post on the topic, I discussed how inverting the polarity of the C-X bond from X=O to X=Be could flip the stereochemical course of the electrocyclic pericyclic reaction of a divinyl system. An obvious question would be: what happens at the half way stage, ie X=CH2? Well, here is the answer. divinylketon CH2 The reaction occurs in two stages (ωB97XD/6-311G(d,p)/SCRF=dichloromethane)[1] but overall is a concerted, albeit asynchronous, reaction. The initial stage is a conrotatory ring closure (as observed with X=O but opposite to X=Be), and reaching what we will call a HI (hidden intermediate). This HI clearly has zwitterionic character, and manifests its presence most obviously at IRC = -3.5 below. CH2CH2G The polarity of this HI is revealed by the dipole moment (6D) and molecular electrostatic potentials, below. The dipole vector goes from -ve to +ve, and the MEP clearly reveals the polarity below. cd7 C2-MEP This ionic HI however is not stable, and in the second stage of the reaction collapses to the neutral bicyclic hydrocarbon shown below. Overall, it amounts to a  2+2 cycloaddition, but with a very unusual pathway in which one C-C bond is very much formed before the other (which is how the reaction escapes the clutches of the Woodward-Hoffmann forbidden-ness). cd8 Why is all this worth this follow-up? Well, one can now start to “design” the reaction. All three carbon atoms with formal charges can be stabilised or destabilised with appropriate substituents. It should not be too difficult to stabilise out the HI into just an I(intermediate), or indeed to remove it from the profile. Nice perhaps for a group of students, who can partition up the substituents amongst themselves and discover if they have the desired effect. And would any of this tinkering change the stereochemical outcome?

References

  1. Henry S. Rzepa., "Gaussian Job Archive for C6H8", 2014. http://dx.doi.org/10.6084/m9.figshare.1128205

Using a polar bond to flip the (stereochemical) outcome of a pericyclic reaction.

Monday, August 4th, 2014
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The outcome of pericyclic reactions con depend most simply on three conditions, any two of which determine the third. Whether the catalyst is Δ or hν (heat or light), the topology determining any stereochemistry and the participating electron count (4n+2/4n). It is always neat to conjure up a simple switch to toggle these; heat or light is simple, but what are the options for toggling the electron count? Here is one I have contrived by playing a game with the periodic table. divinylketon The ring closure of a divinylketone is called the Nazarov reaction, it being promoted thermodynamically by coordination of a Lewis acid to atom X. Divinyl ketone can be regarded as a hidden pentadienyl cation, since the C=O bond is polarised Cδ+Oδ- in the time-honoured manner of organic chemistry. In this (formal) resonance form, it becomes part of a pentadienyl cation and can electrocyclise via a 4-electron reaction involving a stereochemical process known as conrotation. The new bond is formed antarafacially (from opposite faces) at the termini of the pentadienyl cation (ωB97XD/6-311G(d,p)/SCRF=dichloromethane.[1]). Note that for the uncatalysed reaction, the barrier is high and the reaction is endothermic but adding a BF3 to the oxygen lowers the barrier and removes the endothermicity.[2] nazarov-Oa nazarov-Oa nazarov-OBF3 So, one can play a game and ask what would happen if the polarity of the C=X bond were to be reversed. This means going left of oxygen in the periodic table, ending at Be.[3] The reaction has a high barrier, but it is strongly exothermic. However the most noteworthy aspect is that the stereochemistry of the electrocyclisation is now disrotatory, with suprafacial bond formation (from the bottom face in the animation below). The stereochemical outcome of this reaction has been flipped by reversing the polarity of the CX bond. nazarov-Beanazarov-Bea This little example shows how a thought game played using the periodic table can then be reality tested by solving appropriate quantum mechanical equations. In this instance, one is not going to rush into the laboratory to try to replicate the experiment, but it might help catalyse new thoughts amongst the readers of this blog.

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References

  1. Henry S. Rzepa., "Gaussian Job Archive for C5H6O", 2014. http://dx.doi.org/10.6084/m9.figshare.1125721
  2. Henry S. Rzepa., "Gaussian Job Archive for C5H6BF3O", 2014. http://dx.doi.org/10.6084/m9.figshare.1125724
  3. Henry S. Rzepa., "Gaussian Job Archive for C5H6Be", 2014. http://dx.doi.org/10.6084/m9.figshare.1125792

Intersecting paths in molecular energy surfaces.

Sunday, February 16th, 2014
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The potential energy surface for a molecule tells us about how it might react. These surfaces have been charted for thousands of reactions using quantum mechanics, and their basic features are thought to be well understood. Coming across an entirely new feature is rare. So what do you make of the following?

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Three-for-one: a pericyclic brain teaser.

Sunday, January 12th, 2014
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A game one can play with pericyclic reactions is to ask students to identify what type a given example is. So take for example the reaction below.

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A simple pericyclic reaction encapsulating the four thermal selection rules.

Thursday, January 2nd, 2014
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As my previous post hints, I am performing my annual spring-clean of lecture notes on pericyclic reactions. Such reactions, and their stereochemistry, are described by a set of selection rules. I am always on the lookout for a simple example which can most concisely summarise these rules. The (hypothetical) one shown below I think nicely achieves this, and raises some interesting issues in the process.14vs12

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Refactoring my lecture notes on pericyclic reactions.

Sunday, December 29th, 2013
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When I first started giving lectures to students, it was the students themselves that acted as human photocopiers, faithfully trying to duplicate what I was embossing on the lecture theatre blackboard with chalk. How times have changed! Here I thought I might summarise my latest efforts to refactor the material I deliver in one lecture course on pericyclic reactions (and because my notes have always been open, you can view them yourself if you wish).

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