The chemical shift of the benzene proton is about 7.3ppm, significantly downfield from the range of olefinic protons (5.6-58.ppm). This is rationalized as the standard induced diatropic ring current, found in aromatic species. But what should we make of the chemical shift of the protons in cyclobutadiene at 5.8 ppm? Shouldn’t this be much further upfield?

Schleyer and Mo have applied the block localized wavefunction (BLW) technique to aromatic and antiaromatic chemical shifts.¹ In BLW, self-consistent localized orbitals are produced to describe a particular resonance structure. So, for benzene, BLW describes in effect 1,3,5-cyclohexatriene, lacking any resonance energy.  When chemical shifts are computed with the BLW description, the proton chemical shift is 6.6 ppm, and is even more upfield if the geometry is optimized (in D_3h symmetry) with the BLW method (δ=6.2ppm). Furthermore the NICS(0)_πzz (the tensor component corresponding to the perpendicular direction evaluated in the ring center using just the π orbitals) is -36.3 for benzene and 0.0 for the D_3h BLW variant, strongly indicating the role of cyclic delocalization in affecting chemical shifts.

Now for cyclobutadiene, the proton chemical shift of 5.7 ppm becomes 7.4 in the BLW case. NICS(0)_πzz for cyclobutadiene is +46.9 and +1.6 in the BLW case. The problem is that typical alkenes are poor references for cyclobutadiene – when resonance is turned off, the chemical shift does move downfield – indicating the expected upfield shift for cyclobutadiene. Schleyer and Mo suggest that 3,4-dimethylenecyclobutene is a more suitable reference; its ring protons have chemical shifts of 7.65ppm.

They also describe computations of benzocyclobutadiene and tricyclobutenabenzene and offer straightforward rationalizations of their aromatic vs. antiaromatic behavior.

References

(1) Steinmann, S. N.; Jana, D. F.; Wu, J. I.-C.; Schleyer, P. v. R.; Mo, Y.; Corminboeuf, C., "Direct Assessment of Electron Delocalization Using NMR Chemical Shifts," Angew. Chem. Int. Ed., 2009, 48, 9828-9833, DOI: 10.1002/anie.200905390

InChIs

benzene: InChI=1/C6H6/c1-2-4-6-5-3-1/h1-6H
InChIKey=UHOVQNZJYSORNB-UHFFFAOYAH

cyclobutadiene: InChI=1/C4H4/c1-2-4-3-1/h1-4H
InChIKey=HWEQKSVYKBUIIK-UHFFFAOYAI

3,4-dimethylenecyclobutene: InChI=1/C6H6/c1-5-3-4-6(5)2/h3-4H,1-2H2
InChIKey=WHCRVRGGFVUMOK-UHFFFAOYAP

Dynamic effects rear up yet again in a seemingly simple reaction. Singleton has examined the Diels-Alder cycloaddition of acrolein with methyl vinyl ketone to give two cross products 1 and 2.¹ Upon heating the product mixture, 1 is essentially the only observed species. The retro-Diels-Alder is much slower than the conversion of 2 into 1. Using a variety of rate data, the best estimate for the relative formation of 1:2 is 2.5.

The eight possible transition states for this reaction were computed with a variety of methodologies, all providing very similar results. The lowest energy TS is TS3. A TS of type TS4 could not be found; all attempts to optimize it collapsed to TS3.

IRC computations indicate the TS3 leads to 1. The lowest energy TS that leads to 2 is TS6, but a second TS (TS5) lower in energy than TS6 also leads to 1. The other TS are still higher in energy. A Cope-type TS that interconverts 1 and 2 (TS7) was also located. The geometries of these TSs are shown in Figure 1.

TS3 (0.0)	TS5 (4.2)
TS6 (5.2)	TS7 (-0.4)

Figure 1. MP2/6-311+G** optimized geometries and relative energies (kcal mol^-1) of TS3-TS7.¹

Ordinary transition state theory cannot explain the experimental results – the energy difference between the lowest barrier to 1 (TS3) and to 2 (TS6) suggests a rate preference of over 700:1 for 1:2. But the shape of the potential energy surface is reminiscent of others that have been discussed in both my book (Chapter 7) and this blog (see my posts on dynamics) – a surface where trajectories cross a single TS but then bifurcate into two product wells.

To address the chemical selectivity on a surface like this, one must resort to molecular dynamics and examine trajectories. In their MD study of the 296 trajectories that begin at TS3 with motion towards product, 89 end at 1 and 33 end at 2, an amazingly good reproduction of experimental results! Interestingly, 174 trajectories recross the transition state and head back towards reactants. These recrossing trajectories result from “bouncing off” the potential energy wall of the forming C₄-C₅ bond.

In previous work, selectivity in on these types of surfaces was argued in terms of which well the TS was closer to. But analysis of the trajectories in this case revealed that a strong correlation exists between the initial direction and velocity in the 98 cm^-1 vibration – the vibration that corresponds to the closing of the second σ bond, the one between C₆-O₁ (forming 1), in the negative direction, and closing the C­₃-O₈ bond (forming 2) in the positive direction. Singleton argues that this is a type of dynamic matching, and it might be more prevalent that previously recognized.

References

(1) Wang, Z.; Hirschi, J. S.; Singleton, D. A., "Recrossing and Dynamic Matching Effects on Selectivity in a Diels-Alder Reaction," Angew. Chem. Int. Ed., 2009, 48, 9156-9159, DOI: 10.1002/anie.200903293

InChIs

1: InChI=1/C7H10O2/c1-6(8)7-4-2-3-5-9-7/h3,5,7H,2,4H2,1H3
InChIKey=AOFHZPHBPUYLAG-UHFFFAOYAJ

2: InChI=1/C7H10O2/c1-6-3-2-4-7(5-8)9-6/h3,5,7H,2,4H2,1H3
InChIKey=PLZQHPPETMMEED-UHFFFAOYAD

Houk and Doubleday have a nice follow-up study¹ to their previous MD study² of 1,3-dipolar cycloadditions, which I posted on here. They report on the cycloaddition of either acetylene or ethylene to 9 different 1,3-dipoles. Continuing on Houk’s recent thread of looking at distortion energies to attain the TS, they note that a sizable fraction (often over 50%) of the distortion energy is associated with bending the X-Y-Z bond of the dipole, consistent with their earlier work suggesting the importance of this vibration in attaining and crossing the TS. What’s new in this paper is the extensive MD studies, with trajectory studies of all 18 reactions. These revealed again the importance of vibrational energy in this X-Y-Z bending mode in crossing the TS. They also noted the role of translational energy, and the relationship between translational vs. vibrational energy depending on the early/late nature of the TS. Their final point was that the lifetime of any diradical or diradical-like intermediate is so short, less than the time of a bond vibration, so that one can discount any diradical participation. The reaction is concerted.

References

(1) Xu, L.; Doubleday, C. E.; Houk, K. N., "Dynamics of 1,3-Dipolar Cycloadditions: Energy Partitioning of Reactants and Quantitation of Synchronicity," J. Am. Chem. Soc., 2010, ASAP, DOI: /10.1021/ja909372f

(2) Xu, L.; Doubleday, C. E.; Houk, K. N., "Dynamics of 1,3-Dipolar Cycloaddition Reactions of Diazonium Betaines to Acetylene and Ethylene: Bending Vibrations Facilitate Reaction," Angew. Chem. Int. Ed., 2009, 48, 2746-2748, DOI: 10.1002/anie.200805906

An interesting little discussion on the meaning of “protobranching” appears in a comment¹ and reply² in J. Phys. Chem. A. Fishtik¹ calls out the concept of protobranching on three counts:

1. It is inconsistent to count a single protobranch for propane, but then not have three protobranches in cyclopropane
2. It is inappropriate to utilize methane as a reference species.
3. Group additivities work well.

I tend to side more with Schleyer² in his rebuttal of these charges, and so will present from this perspective. First off, Schleyer argues that he can define protobranch anyway he wants! (He in fact cites a quote of Humpty Dumpty from Lewis Carroll to support this stance!) Schleyer is of course correct. Fishtik should really have argued “Does Schleyer’s definition of protobranch add to our understanding of strain?” So Fishtik claims that there is an internal inconsistency in Schleyer’s definition – taking the view point that the C-(C)₂(H)₂ group is identical to the protobranch. Schleyer counters that no, the protobranch is this group along with the caveat that the two terminal carbons are not connected, like they are in cyclopropane. I really prefer Gronert’s approach here – where he argues for just what are the implications of Schleyer’s definition (see this post).

Fishtik refuses to use methane as a reference since it is a unique molecule. Again, if one takes the group-centric view, then methane possesses a group that no other compound has. But Schleyer counters that one is free to choose whatever reference one thinks is appropriate, just be sure to understand what properties are conserved or not conserved when using that reference selection. To me, this is really the key for the entire discussion: choose one’s references in such a way as to minimize differences between your reference compound(s) and the molecule(s) you are trying to explore to just the property of interest. So, if one is interested in quantifying ring strain, the reference compounds should be not only be strain-free but they should differ in no other way from the cyclic molecule other than the presence of the ring! Unfortunately, there is no unique or non-arbitrary way to do this! Schleyer’s approach and Fishtik’s approach differ in just what properties they believe are important to conserve and which properties they are going to lump into the concept “ring strain”.

Fishtik shows a whole slew of reactions that demonstrate the consistency of group additivity methods. Schleyer correctly points out that these examples are really intimately related and represent only one type of definition. Again, there is really no unique set of references, and many, many different models have been developed, all of which can match experimental data quite well – like for example heats of formation. The key is what these models say in terms of interpreting, say, these heats of formation. Can one rationalize trends and make predictions with the model? If so, then it has utility. If not, then the model should be discarded. Ultimately, Fishtik’s argument is that the protobranching model does not assist us in understanding strain – Schleyer would obviously beg to differ!

References

(1) Fishtik, I., "Comment on "The Concept of Protobranching and Its Many Paradigm Shifting Implications for Energy Evaluations"," J. Phys. Chem. A, 2010, ASAP, DOI: 10.1021/jp908894q

(2) Schleyer, P. v. R.; McKee, W. C., "Reply to the "Comment on ‘The Concept of Protobranching and Its Many Paradigm Shifting Implications for Energy Evaluations’"," J. Phys. Chem. A, 2010, ASAP, DOI: 10.1021/jp909910f

One more study of cyclodiene reactions with ketenes that suggest the occurrence of dynamic effects.¹ The reaction of cyclopentadiene with t-butylcyanoketene 1 gives cyclobutanone 2 solely. In contrast, the reaction of 1,3-cyclophexadiene with 1 gives the cyclobutanone 3 and a small amount (less than 25%) of the ether 4. Warming the reaction from -20 °C to 20 °C leads to loss of 3 and an increase in 4. This is in distinct contrast with the reaction of cyclopentadiene with diphenylketene,² where the ether product is the major product and the cyclobutenone is the minor product (see Chapter 7.3.5.2 in my book).

To help understand this situation, the authors optimized the structures of the critical points on the surface of the cyclohexadiene reaction at MPWB1K/6-31+G(d,p) – though once again, there are no supporting materials so I cannot supply the 3-D structures in the blog! 4 is predicted to be 3.4 kcal mol^-1 more stable than 3, which accounts for it being the thermodynamic product, consistent with experiment. Only two transition states are found. The first TS, with a barrier of 23.2 kcal mol^-1, connects reactants with 3. The second transition state corresponds to the oxy-Cope rearrangement that takes 3 into 4. This surface is reminiscent of many others that display dynamic effects (again see my book and also these posts). Unfortunately, the authors have not performed any trajectory calculation. But one might expect that most trajectories cross the first transition state and fall into the well associated with 3. Some of these molecules then go on to cross the second barrier to form 4. But some trajectories cross the first TS and then veer off into the slightly lower well associated with 4, being directly formed from reactant. This would be a manifestation of dynamic effects, and is worth further study.

References

(1) Marton, A.; Pârvulescu, L.; Draghici, C.; Varga, R. A.; Gheorghiu, M. D., "Reaction of Moore’s ketene (tert-butylcyanoketene) with 1,3-cyclopentadiene and 1,3-cyclohexadiene. Is periselectivity controlled by the dynamic of trajectories at the bifurcation point?," Tetrahedron, 2009, 65, 7504-7509, DOI: 10.1016/j.tet.2009.07.020.

(2) Ussing, B. R.; Hang, C.; Singleton, D. A., "Dynamic Effects on the Periselectivity, Rate, Isotope Effects, and Mechanism of Cycloadditions of Ketenes with Cyclopentadiene," J. Am. Chem. Soc., 2006, 128, 7594-7607, DOI: 10.1021/ja0606024.

The nature of reactions of indolynes is the subject of two recent computational/experimental studies. There are three isomeric indolynes 1a-c which are analogues of the more famous benzyne (which I discuss in significant detail in Chapter 4.4 of my book).

One might anticipate that the indolynes undergo comparable reactions as benzyne, like Diels-Alder reactions and nucleophilic attack. In fact the indolynes do undergo these reactions, with unusual regiospecificity. For example, the reaction of the substituted 6,7-indolyne undergoes regioselective Diels-Alder cycloaddition with substituted furans (Scheme 1), but the reaction with the other indolynes gives no regioselection. ¹ Note that the preferred product is the more sterically congested adduct.

Scheme 1

In the case of nucleophilic addition, the nucleophiles add specifically to C₆ with substituted 6,7-indolynes (Scheme 2), while addition to 4,5-indolynes preferentially gives the C₅-adduct (greater than 3:1) while addition to the 5,6-indolynes preferentially gives the C₅-adduct), but with small selectivity (less than 3:1).²

Scheme 2

The authors of both papers – Chris Cramer studied the Diels-Alder chemistry and Ken Houk studied the nucleophilic reactions – employed DFT computations to examine the activation barriers leading to the two regioisomeric products. So for example, Figure 1 shows the two transition states for the reaction of 2c with 2-iso-propyl furan computed at MO6-2X/6-311+G(2df,p).

ΔG‡ = 9.7

ΔG‡ = 7.6

Figure 1. MO6-21/6-311+G(2df,p) optimized TSs for the reaction of 2-iso-propylfuran with 2c. Activation energy (kcal mol^-1) listed below each structure.¹

The computational results are completely consistent with the experiments. For the Diels-Alder reaction of 2-t-butylfuran with the three indolynes 2a-c, the lower computed TS always corresponds with the experimentally observed major product. The difference in the energy of the TSs leading to the two regioisomers for reaction with 2a and 2b is small (less than 1 kcal mol^-1), consistent with the small selectivity. On the other hand, no barrier could be found for the reaction of 2-t-butylfuran with 2c that leads to the major product. Similar results are also obtained for the nucleophilic addition – in all cases, the experimentally observed major product corresponds with the lower computed activation barrier.

So what accounts for the regioselectivity? Both papers make the same argument, though couched in slightly different terms. Houk argues in terms of distortion energy – the energy needed to distort reactants to their geometries in the TS. As seen in Figure 2, the benzyne fragment of 2a is distorted, with the C-C-C angle at C₄ of 125° and at C₅ of 129°. In the transition states, the angle at the point of nucleophilic attack widens. Since the angle starts out wider at C₅, attack there is preferred, since less distortion is needed to achieve the geometry of the TS.

2a
TS at C4 ΔG‡ = 12.9	TS at C5 ΔG‡ = 9.9

Figure 2. B3LYP/6-31G(d) optimized structures of 2a and the TSs for the reaction of aniline with 2a. Activation energy in kcal mol^-1.²

Cramer argues in terms of the indolyne acting as an electrophile. Increasing substitution at the furan 2-position makes is better at stabilizing incipient positive charge that will build up there during a (very) asymmetric Diels-Alder transition state. This explains the increasing selectivity of the furan with increasing substitution. The indolyne acting as an electrophile means that the attack will lead from the center will lesser charge. In 2c, the C-C-C angle at C₆ is 135.3°, while that at C₇ is 117.2°. This makes C₇ more carbanionic and C₆ more carbocationic; therefore, the first bond made is to C₆, leading to the more sterically congested product. Note that Houk’s argument applies equally well, as C₆ is predistorted to the TS geometry.

References

(1) Garr, A. N.; Luo, D.; Brown, N.; Cramer, C. J.; Buszek, K. R.; VanderVelde, D., "Experimental and Theoretical Investigations into the Unusual Regioselectivity of 4,5-, 5,6-, and 6,7-Indole Aryne Cycloadditions," Org. Lett., 2010, 12, 96-99, DOI: 10.1021/ol902415s

(2) Cheong, P. H. Y.; Paton, R. S.; Bronner, S. M.; Im, G. Y. J.; Garg, N. K.; Houk, K. N., "Indolyne and Aryne Distortions and Nucleophilic Regioselectivites," J. Am. Chem. Soc., 2010, 132, 1267-1269, DOI: 10.1021/ja9098643

InChIs

1a: InChI=1/C8H5N/c1-2-4-8-7(3-1)5-6-9-8/h2,4-6,9H
InChIKey=RNDHGGYOIRREHC-UHFFFAOYAU

1b: InChI=1/C8H5N/c1-2-4-8-7(3-1)5-6-9-8/h3-6,9H
InChIKey=WWZQFJXNXMIWCD-UHFFFAOYAO

1c: InChI=1/C8H5N/c1-2-4-8-7(3-1)5-6-9-8/h1,3,5-6,9H
InChIKey=UHIRLIIPIXHWLT-UHFFFAOYAH

2a: InChI=1/C9H7N/c1-10-7-6-8-4-2-3-5-9(8)10/h3,5-7H,1H3
InChIKey=VTVUPAJGRVFCKI-UHFFFAOYAJ

2b: InChI=1/C9H7N/c1-10-7-6-8-4-2-3-5-9(8)10/h4-7H,1H3
InChIKey=KKPOWDDYMOXTFW-UHFFFAOYAN

2c: InChI=1/C9H7N/c1-10-7-6-8-4-2-3-5-9(8)10/h2,4,6-7H,1H3
InChIKey=MDAHOGWZOBLIEX-UHFFFAOYAZ

So yesterday mornings “Future of Scholarly Publishing” was quite interesting. Steve Heller gave his usual enjoyable presentation of InChI and the InChI Trust. The establishment of the Trust ensures that progress and technical support for InChI continues on.

Alex Wade from Microsoft gave a great overview of the activities Microsoft has ongoing in the area of scholarly communication. I was impressed if not even overwhelmed with all that Microsoft is doing. If you were worried about Microsoft taking over the world, then this talk will only reinforce that concern! I will post a link to his talk once it is made available. UPDATE: Here is Alex’s PowerPoint presentation.

Next was Peter Murray-Rust, and this was a typical Peter talk. He started off by truly going after all scientific publishers for restrictions to and copyright notices plastered all over supplementary materials. These materials are almost exclusively data, and data cannot be copyrighted. Peter pleaded with publishers to allow free and unrestricted access to these materials and I wholeheartedly second this! Peter then demonstrated a number of chemistry semantic tools. His talk will be posted online, and I’ll get the URL here when it’s available.

The last of the talks I was able to see before leaving for the airport was by Joe Townsend. He demonstrated the new Chem4Word plugin (now rebranded “Chemistry Add-in for Word”). This tool allows for chemistry semantics to be placed into a docx file, with all chemistry preserved as xml. This is an amazing first step towards providing authors the proper tools to create data- and chemistry-rich documents that preserve chemical knowledge for distribution and archiving. The plugin is available here, and is only applicable for Word 2007, and that poses an interesting problem as pointed out during the Q&A session – ACS pubs cannot accept docx files, so all that semantics will be lost. As was mentioned in the talk, that’s data destruction, and it’s time for authors and readers to demand better from the STM publishers!

Not particularly strong programming at the year’s spring ACS meeting – but one great session in the organic division yesterday. This was the awards session in honor of John Baldwin getting the James Flack Norris Award for physical organic chemistry.

First to speak was James Duncan, who discussed his recent CASSCF computations looking for pseudopericylic [3,3]-sigmatropic migrations. I will be commenting on his latest work in a post that will appear soon.

I had to skip the next talk, but came back to hear John Brauman discuss recent work on the solvation effect in the S_N2 reaction. This is an interesting case of where the screening of larger substituents is counterbalanced by geometric changes that lead to greater charge distribution. The net effect is that they cancel each other out, and the methyl,ethyl, iso-propyl, butyl β-effect is negligible.

Next was Peter Schreiner who discussed his carbene work, specifically the enormous tunneling effect observed in hydroxymethylene (see this post). He discussed some new work, that is if anything even more fantastic on methylhydroxycarbene – look for this work perhaps later in 2011.

Last to speak was John Baldwin – and he described his truly tour de force efforts in examining the [1,3]-rearrangements of vinylcyclopropane and vinylcyclobutane. The former work is described in my book, while the later study is still ongoing.

John’s work is amazingly painstaking and careful. I am truly in awe of his dedication in taking on extremely difficult studies that require enormous care. John has really taught us a lot – not just about these rearrangements (they involve diradicals on a flat plateau demanding dynamic analysis – but how to think about a study and then carry it out to fruition so that all details are assessed. A truly deserving recipient!

Here’s another attempt (almost successful!) in creating a planar cyclooctatetraene. Nishininaga and Iyoda have fused silicon and sulfur bridges to the COT framework, hoping to force the 8-member ring out of its preferred tub-shape into a planar structure.¹ They report the synthesis of 1, 2, and 3b along with their x-ray structures. They also calculated the structures at B3LYP/6-31G(d,p) for 1-4 , and these optimized structures are shown in Figure 1.

1 18° 19°	2 3.0° 4.3°
3a 7.0° (for 3b) 3.2° (for 3a)	4 39° 40°

Figure 1. B3LYP/6-31G(d,p) optimized geometries of 1-4. The experimental (top) and computed (Bottom in italics) value of α are listed for each compound.¹

The bent angle α is defined at the angle between the two planes that define the bottom of the tub and one of the sides. For COT itself, this angle is 40°, decidedly non-planar – as expected for a molecule avoiding the antiaromatic character it would have in its planar conformation. The computed and experimental values of α are shown in Figure 1. 4 is tub shaped. The value of α for 1 is about 18° – still tub shaped but flattened. But 2 and 3 are nearly planar, with experimental values of α about 3° and the computed values are similar.

So what is the character of the 8-member ring in these compounds. The computed NICS(0) values are 3.8 ppm for 4, the expected small value for a non-aromatic compound. (Note that the NICS value for COT is 2.9 ppm.) The values are much more positive for the other compounds: 12.7 ppm for 1, 17.4 ppm for 2, and 15.4 ppm for 3a. These compounds therefore display antiaromatic character yet they are isolable compounds!

References

(1) Ohmae, T.; Nishinaga, T.; Wu, M.; Iyoda, M., "Cyclic Tetrathiophenes Planarized by Silicon and Sulfur Bridges Bearing Antiaromatic Cyclooctatetraene Core: Syntheses, Structures, and Properties," J. Am. Chem. Soc., 2009, 132, 1066-1074, DOI: 10.1021/ja908161r

InChIs

1: InChI=1/C20H16S4Si2/c1-25(2)9-5-21-17-13(9)14-10(25)6-22-18(14)20-16-12(8-24-20)26(3,4)11-7-23-19(17)15(11)16/h5-8H,1-4H3/b19-17-,20-18-
InChIKey=DAVVQYAXJVCICC-CLFAGFIQBV

2: InChIKey=PBXVOLKKILUEGI-RFIZXXDFBX

3a: InChI=1/C16H4O4S6/c17-25(18)5-1-21-13-9(5)10-6(25)2-23-15(10)16-12-8(4-24-16)26(19,20)7-3-22-14(13)11(7)12/h1-4H/b14-13-,16-15-
InChIKey=VIDZCGPUBZEACC-RFIZXXDFBR

3b: InChI=1/C28H36O4S6Si4/c1-39(2,3)25-21-13-14-19(35-26(40(4,5)6)22(14)37(21,29)30)20-16-15-18(17(13)33-25)34-27(41(7,8)9)23(15)38(31,32)24(16)28(36-20)42(10,11)12/h1-12H3/b18-17-,20-19-
InChIKey=XXCFCYWSFICMIO-RXGVRZIVBS

4: InChI=1/C16H8S4/c1-5-17-13-9(1)10-2-6-18-14(10)16-12(4-8-20-16)11-3-7-19-15(11)13/h1-8H/b10-9-,12-11-,15-13-,16-14-
InChIKey=RSNUTSCZGMAXQJ-FNJUYVFOBD

The keto-enol tautomerization is an interesting system for probing relative energies of subtle effects, playing off different bond type (and their associated strengths) with conjugation and hydrogen bonding and strain. Lawrence and Hutchings have now extended this to include the interplay of aromaticity and antiaromaticity in the keto-enol tautomerization of benzodifurantrione 1.¹ The keto form 1k looks to be the favotable tautomer, containing an aromatic phenyl ring. The enol tautomer 1e requires the loss of that aromatic ring. Nonetheless, the enol structure is the only tautomer present in the crystal phase, and the enol tautomer is the dominant structure (if not the exclusive structure) in all solvents tested, including acetic acid, acetone, acetonitrile, chloroform, DMF, DMSO, propanol and toluene. The only solvents where the keto form is dominant are toluene and o-dichlorobenzene.

So, how does one rationalize this equilibrium? The B3LYP/6-311G(2d,p) structure of the two tautomers are shown in Figure 1. Note that there are two isomers of the enol form, differing on the orientation of the hydroxyl hydrogen. The syn isomer is the lowest energy form, in both the gas phase and in solution (PCM modeling acetonitrile, chlorobenzene and THF). So the enol form is the lowest energy structure when there are no special interactions involving hydrogen bonding or dipolar interactions with the solvent – there is an inherent energy preference for 1e.

1k
1e-anti	1e-syn

Figure 1. B3LYP/6-311G(2d,p) structures of the tautomers of 1.¹

To address that, they computed the NICS(0) values for each ring in the two tautomers. The pendant phenyl group is aromatic in both structures, as expected. The lactone ring has NICS values near 0 in both structures. The interior phenyl ring is aromatic (NICS = -7.5) in 1k but is non-aromatic in 1e, with NICS=-0.4. So the aromaticity of this ring is lost upon enolization, and thus would favor 1k. However, the terminal ring in the keto tautomer has NICS = +7.2, suggesting that it is antiaromatic, and upon enolization, the ring becomes slightly aromatic, with NICS = -2.1. Thus, the keto form is plagued by an antiaromatic ring, which is then lost in the enol form. The result is the interplay between losing an aromatic ring and its stabilization when the enol is formed balanced by also losing an antiaromatic ring with its destabilization. The authors do not offer any quantization (rightfully so!) of the stabilization/destabilization associated with these rings. But very subtle effects are clearly at play.

References

(1) Lawrence, A. J.; Hutchings, M. G.; Kennedy, A. R.; McDouall, J. J. W., "Benzodifurantrione: A Stable Phenylogous Enol," J. Org. Chem., 2010, 75, 690–701, DOI: 10.1021/jo9022155

InChIs

1k: InChI=1/C16H8O5/c17-14-10-7-11-9(6-12(10)21-16(14)19)13(15(18)20-11)8-4-2-1-3-5-8/h1-7,13H
InChIKey=GNWKSKHSRUSFBC-UHFFFAOYAC

1e: InChI=1/C16H8O5/c17-14-10-7-11-9(6-12(10)21-16(14)19)13(15(18)20-11)8-4-2-1-3-5-8/h1-7,17H
InChIKey=MZLQKOSFMRKQIO-UHFFFAOYAB