The Schreiner group has again reported an amazing experimental and computational study demonstrating a fascinating quantum mechanical tunneling effect, this time for the trifluoromethylhydroxycarbene (CF₃COH) 2.¹ (I have made on a number of posts discussing a series of important studies in this field by Schreiner.) Carbene 2 is formed, in analogy to many other hydroxycarbenes, by flash vapor pyrolysis of the appropriate oxoacid 1 and capturing the products on a noble gas matrix.

Carbene 2t is observed by IR spectroscopy, and its structure is identified by comparison with the computed CCSD(T)/cc-pVTZ frequencies. When 2t is subjected to 465 nm light, the signals for 2t disappear within 30s, and two new species are observed. The first species is the cis conformer 2c, confirmed by comparison with its computed CCSD(T)/cc-pVTZ frequencies. This cis conformer remains even with continued photolysis. The other product is determined to be trifluoroacetaldehyde 3. Perhaps most interesting is that 2t will convert to 3 in the absence of light at temperatures between 3 and 30 K, with a half-life of about 144 h. There is little rate difference at these temperatures. These results are quite indicative of quantum mechanical tunneling.

To aid in confirming tunneling, they computed the potential energy surface at CCSD(T)/cc-pVTZ. The trans isomer is 0.8 kcal mol^-1 lower in energy that the cis isomer, and this is much smaller than for other hydroxycarbenes they have examined. The rotational barrier TS1 between the two isomer is quite large, 26.4 kcal mol^-1, precluding their interchange by classical means at matrix temperatures. The barrier for conversion of 2t to 3 (TS2) is also quite large, 30.7 kcal mol^-1, and insurmountable at 10K by classical means. No transition state connecting 2c to 3 could be located. These geometries and energies are shown in Figure 1.

2c 0.8

TS1 26.4

2t 0.0

TS2 30.7

3 -49.7

Figure 1. Optimized geometries at CCSD(T)/cc-pVTZ. Relative energies (kcal mol^-1) of each species are listed as well.

WKB computations at M06-2X/6-311++G(d,p) predict a half-life of 172 h, in nice agreement with experiment. The computed half-life for deuterated 2t is 10⁶ years, and the experiment on the deuterated analogue revealed no formation of deuterated 3.

The novel component of this study is that tunneling is conformationally selective. The CF₃ group stabilizes the cis form probably through some weak H^…F interaction, so that the cis isomer can be observed, but no tunneling is observed from this isomer. Only the trans isomer has the migrating hydrogen atom properly arranged for a short hop over to the carbon, allowing the tunneling process to take place.

References

1) Mardyukov, A.; Quanz, H.; Schreiner, P. R., "Conformer-specific hydrogen atom tunnelling in trifluoromethylhydroxycarbene." Nat. Chem. 2017, 9, 71–76, DOI: 10.1038/nchem.2609.

InChIs

1: =1S/C3HF3O3/c4-3(5,6)1(7)2(8)9/h(H,8,9)
InChIKey=GVDJEHMDNREMFA-UHFFFAOYSA-N

2: InChI=1S/C2HF3O/c3-2(4,5)1-6/h6H
InChIKey=FVJVNIREIXAWKU-UHFFFAOYSA-N

3: InChI=1S/C2HF3O/c3-2(4,5)1-6/h1H
InChIKey=JVTSHOJDBRTPHD-UHFFFAOYSA-N

Carbenes remain an active area of interest for computational chemists, as seen in Chapter 5 of my book. For many carbenes, the triplet is the ground state, and that is true of diphenylcarbene 1. Can solvent play a role in the stability of carbene spin states? Surprisingly, the answer, provided in a recent paper by Sander,¹ is yes!

In the gas phase, the singlet-triplet gap of 1 is computed to be 5.62 kcal mol^-1 at (U)B3LYP/6-311++G(d,p) (and this reduces to 5.06 at (U)B3LYP+D3/6-311++G(d,p)) with the ground state as a triplet. If a single methanol molecules is allowed to approach 1, then the complex involving the singlet has a short hydrogen bond distance of 1.97 Å but the triplet has a much longer distance of 2.33 Å. These structures are shown in Figure 1. This manifests in a dramatic change in the relative stability, with the singlet complex now 0.26 kcal mol^-1 (0.44 with the D3 correction) lower in energy than the triplet.

Singlet-1:methanol

Triplet-1:methanol

Figure 1. (U)B3LYP/6-311++G(d,p) optimized geometries of the compelxes of methanol with singlet or triplet 1.

IR spectroscopy of 1 in an argon matrix doped with a small amount of methanol confirms the presence of the singlet carbene, and detailed description of the difference in the reactivities of the singlet and triplet are provided.

References

(1) Costa, P.; Sander, W. "Hydrogen Bonding Switches the Spin State of Diphenylcarbene from Triplet to Singlet," Angew. Chem. Int. Ed. 2014, 53, 5122-5125, DOI: 10.1002/anie.201400176.

InChIs

1: InChI=1S/C13H10/c1-3-7-12(8-4-1)11-13-9-5-2-6-10-13/h1-10H
InChIKey=XMGMFRIEKMMMSU-UHFFFAOYSA-N

Dihdroxycarbene was the subject of a post a few years ago relating to how this carbene does not undergo tunneling,¹ while related hydroxycarbene do undergo a tunneling rearrangement.

Now we have a gas-phase microwave determination of the trans,cis isomer of dihydroxycarbene.² The computed CCSD(T)/cc-pCVQZ structure is shown in Figure 1. What is truly remarkable here is the amazing agreement between the experimental and computed structure – as seen in Table 1.The bond distance are in agreement within 0.001 Å and the bond angles agree within 0.3°! Just further evidence of the quality one can expect from high-level computations. And computing this structure was certainly far easier than the experiments!

Figure 1. CCSD(T)/cc-pCVQZ optimized geometry of dihydroxycarbene.

Table 1. Experimental and computed (CCSD(T)/cc-pCVQZ) geometric parameters of dihydroxycarbene.^a

References

(1) Schreiner, P. R.; Reisenauer, H. P. "Spectroscopic Identification of Dihydroxycarbene," Angew. Chem. Int. Ed. 2008, 47, 7071-7074, DOI: 10.1002/anie.200802105.

(2) Womack, C. C.; Crabtree, K. N.; McCaslin, L.; Martinez, O.; Field, R. W.; Stanton, J. F.; McCarthy, M. C. "Gas-Phase Structure Determination of Dihydroxycarbene, One of the Smallest Stable Singlet Carbenes," Angew. Chem. Int. Ed. 2014, 53, 4089-4092, DOI: 10.1002/anie.201311082.

InChIs

Dihydroxycarbene: InChI=1S/CH2O2/c2-1-3/h2-3H
InChIKey=VZOMUUKAVRPMBY-UHFFFAOYSA-N

Can one identify a labile bond in a molecule without computing activation barriers? Markopoulos and Grunenberg suggest that examination of the bond length and its associated relaxed force constant might provide some guidance.¹

The relaxed force constant comes from identifying the force constant for some coordinate while allowing for other coordinates to relax. Badger’s rule relates the (normal) force constant to bond distance (k = a/(r_eq – d)³). For a series of 36 molecules, covering 71 C-C single bonds, Badger’s rule fits the data well, except for a set of molecules which undergo rapid Cope rearrangements (like bullvalene and semibullvalene). For these molecules, the relaxed force constants are much lower than Badger’s rule predicts, and indicates a weakened bond. This gives rise to their low activation barriers.

Another example is provided with the highly strained polycyclic hydrocarbon 1. This compound is predicted (B3LYP/6-31G(d)) to undergo a [1,2]-shift to give the carbene 2 (see Figure 1), and this is extremely exothermic: -105.7 kcal mol^-1, reflecting the enormous strain of 1. The barrier, through TS1 (Figure 1), is only 6.7 kcal mol^-1. This rearrangement was predicted by examining the relaxed force constants which identified a very weak bond, despite a short bond distance of 1.404 Å. It is unlikely that without this guidance, one would have predicted that this short bond is likely to rupture and produce this particular product.

1	2
TS1

Figure 1. B3LYP/6-31G(d) optimized structures of 1, 2, and TS1.

References

(1) Markopoulos, G.; Grunenberg, J. "Predicting Kinetically Unstable C-C Bonds from the Ground-State Properties of a Molecule," Angew. Chem. Int. Ed. 2013, 52, 10648-10651, DOI: 10.1002/anie.20130382.

InChIs

1: InChI=1S/C14H12/c1-2-8-11-5-3-9-7(1)10(9)4-6-12(8,11)14(8,11)13(7,9)10/h1-6H2
InChIKey=LNBZAENQMFDBJW-UHFFFAOYSA-N

2: InChI=1S/C14H12/c1-3-11-12-4-2-9-7-8(1,9)10(9)5-6-13(11,12)14(10,11)12/h1-6H2
InChIKey=UKVODHRLGFPZPT-UHFFFAOYSA-N

The singlet and triplet carbene is the topic of Chapter 4, especially sections 1 and 2. The ground state of methylene is the triplet, with one electron in the σ-orbital and one electron in the π-orbital, with the spins aligned. The lowest singlet state places the pair of electrons in the σ-orbital, and this state is about 9 kcal mol^-1 higher in energy than the triplet. The next lowest singlet state has one electron in each of the σ- and π-orbitals, with the spins aligned. The singlet state with both electrons in the π-orbital is the highest of these four states, some 60 kcal mol^-1 above the ground state triplet.

Hoffmann and Borden now pose the question “Can the doubly occupied π carbene (¹A₁-σ⁰π²) be the ground state with appropriate substitution?” The answer they find is yes!¹

The trick is to find a combination of substituents that will raise the energy of the σ-orbital and lower the energy of the π-orbital. The latter effect can be enhanced if the π-orbital can be a part of an aromatic (6e^–) ring.

Two of the best possibilities for identifying a ground state ¹A₁-σ⁰π² carbene are 1 and 2. The CASSCF/6-31G(d) optimized geometries of these two are shown in Figure 1. In 1, the nitrogen lone pairs act to destabilize the σ-orbital, while the aldehyde group acts as a withdrawing group to stabilize the π-orbital. The result is that the ¹A₁-σ⁰π⁶ state of 1 is predicted to be about 8 kcal mol^-1 more stable than the triplet state, as per CASPT2 and CCSD(T) computations.

An ever greater effect is predicted for 2. Here the nitrogen lone pairs adjacent to the carbene act to destabilize the σ-orbital. The empty π-orbital on B lowers the energy of the carbene π-orbital by making it part of the 6-electron aromatic ring. The ¹A₁-σ⁰π⁶ state of 2 is predicted to be about 25 kcal mol^-1 more stable than its triplet state!

1

2

Figure 1. CASSCF/6-31G(d) optimized geometries of the ¹A₁-σ⁰π⁶ states of 1 and 2.

References

(1) Chen, B.; Rogachev, A. Y.; Hrovat, D. A.; Hoffmann, R.; Borden, W. T. "How to
Make the σ⁰π² Singlet the Ground State of Carbenes," J. Am. Chem. Soc. 2013, 135, 13954-13964, DOI: 10.1021/ja407116e.

InChIs

1: InChI=1S/C5H2N2O2/c8-1-4-5(2-9)7-3-6-4/h1-2H
InChIKey=QDSVROXEBBWIOO-UHFFFAOYSA-N

2: InChI=1S/C3H3BN2/c1-4-2-6-3-5-1/h1-2,4H
InChIKey=MQJXDZBYOSOLST-UHFFFAOYSA-N

Can a remote substituent affect the singlet-triplet spin state of a carbene? Somewhat surprisingly, the answer is yes. Sheridan has synthesized and characterized the meta and para methoxy-substituted phenyltrifluoromethyl)carbenes 1 and 2.¹ The UV-Vis spectrum of 1 is consistent with a triplet as its EPR and reactivity with oxygen. However, the para isomer 2 gave no EPR signal and failed to react with oxygen or hydrogen, suggestive of a singlet.

The conformations of 1 and 2 were optimized at B3LYP/6-31+G(d,p) and the lowest energy
singlet and triplet conformers are shown in Figure 1. The experimental spectral features of 1 match up best with the computed features of the triplet, and the same is true for the singlet of 2.

1singlet	1triplet
2singlet	2triplet

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

The triplet of 1 is estimated to be about 4 kcal mol^-1 below that of the singlet – larger than the general overestimation of the stability of triplets that beleaguer B3LYP. For 2, B3LYP predicts a singlet ground state.

The isodesmic reactions 1 and 2 help understand the strong substituent effect. For 1, the meta substituent destabilizes both the singlet and triplet by a small amount. For 2, the para methoxy group stabilizes the triplet slightly, but stabilizes the singlet by a large amount. This stabilization is likely the result of the contribution of a second resonance structure 2b. A large rotational barrier for both the methyl methyl and the trifluoromethyl groups supports the participation of 2b.

References

(1) Song, M.-G.; Sheridan, R. S., "Regiochemical Substituent Switching of Spin States in
Aryl(trifluoromethyl)carbenes," J. Am. Chem. Soc. 2011, 133, 19688-19690, DOI: 10.1021/ja209613u

InChIs

1: InChI=1/C9H7F3O/c1-13-8-4-2-3-7(5-8)6-9(10,11)12/h2-5H,1H3
InChIKey=CAHMVAJXXQQHDW-UHFFFAOYAA

2: InChI=1/C9H7F3O/c1-13-8-4-2-7(3-5-8)6-9(10,11)12/h2-5H,1H3
InChIKey

Somehow I missed this paper when it came out a few months ago, even though I was aware it was coming – as I mentioned it in one of my previous posts!

Anyways, Schreiner and Allen reported on their third study of hydroxyl carbenes (see these posts on dihydroxymethylene and hydroxymethylene), this time examining phenylhydroxycarbene.¹ As I covered in my book, there is a lot of work on phenylcarbenes which typically ring expand to the cycloheptatetraene, see Reaction 1. One might expect phenylhydroxycarbene to do the same thing, i.e. 1 converting into 2 (Reaction 2). 1 is prepared by high-vacuum flash pyrolysis of phenylglyoxylic acid 3 and then capturing the product in an argon matrix at 11 K (Reaction 3).

The carbene 1 is identified through comparison of its experimental and computed (anharmonic frequencies at CCSD(T)/cc-pVDZ) IR frequencies.

No ring expansion is observed at all – Reaction 2 does not occur. Instead, 1 rearranges to benzaldehyde 4 (Reaction 4) at 11 K with a half life of 2.46 h (and a half life of 2.55 h at 20 K). The deuterated analogue does not convert to benzaldehyde and 1-d appears to be completely stable.

So, what is going on? The cis and trans forms of 1 interconvert through a barrier of 22.7 kcal mol^-1. The trans isomer can convert to benzaldehyde (the reaction is very exothermic: -50.8 kcal mol^-1) with a barrier of 28.8 kcal mol^-1 through TS1, shown in Figure 1. The cis isomer can cleave into benzene and CO (not observed) with a huge barrier of 55 kcal mol^-1. All of these barrier were computed at CCSD(T)/cc-pVQZ.

TS1

Figure 1. MP2/cc-pVDZ optimized transition state for the conversion of 1 into 4.

Benzaldehyde seems to be produced by passing through a huge barrier, something that is impossible from a thermal perspective (we’re at 11 K!). But this can be accomplished by tunneling. Tunneling probabilities were computed from the MP2/aug-cc-pVDZ intrinsic reaction path with barrier penetration integrals computed with the WKB approximation. The bottom line: the computed half-life is 3.3 h and the deuterated species is computed to have a half-life of 8700 years(!), both in excellent agreement with experimental observation. Quantum mechanical tunneling is clearly the explanation for this chemistry.

This is another fine example of the power of joint experimental/computational studies. And be on the look-out for an even more exciting case from this group. I met with Wes Allen on my recent trip to the University of Georgia and was entertained with another hydroxycarbene that undergoes quite novel tunneling!

References

(1) Gerbig, D.; Reisenauer, H. P.; Wu, C.-H.; Ley, D.; Allen, W. D.; Schreiner, P. R., "Phenylhydroxycarbene," J. Am. Chem. Soc., 2010, 132, 7273-7275, DOI: 10.1021/ja9107885

InChIs

1: InChI=1/C7H6O/c8-6-7-4-2-1-3-5-7/h1-5,8H
InChIKey=QVZIGMRPQWIGCV-UHFFFAOYAE

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

3: InChI=1/C8H6O3/c9-7(8(10)11)6-4-2-1-3-5-6/h1-5H,(H,10,11)/f/h10H
InChIKey=FAQJJMHZNSSFSM-KZFATGLACS

4: InChI=1/C7H6O/c8-6-7-4-2-1-3-5-7/h1-6H
InChIKey=HUMNYLRZRPPJDN-UHFFFAOYAE

Does the Carbon-Sulfur triple bond exist? There’s probably little doubt it does in the CS molecule. But now Schreiner and Mloston have offered up the H-C≡S-OH species as a possibility.¹ Obtained by flash photolysis of 1, giving 2, and upon irradiation at 254 nm, H-C≡S-OH 3 is the observed species and not the expected carbene HO-C-SH 4. 3 is confirmed by excellent agreement between the observed and computationally predicted IR spectra.

The CCSD(T)/cc-pVTZ structures of 3 and 4 are shown in Figure 1. It is interesting that the carbene is not observed, even though it is 26.6 kcal mol^-1 more stable than 3.

3

4

Figure 1. CCSD(T)/cc-PVTZ optimized structures of 3 and 4.¹

So is there a triple bond? The short C-S distance (1.547 Å) is very similar to that in CS (1.545 Å). NBO analysis indicates a triple bond. But the MOs indicate significant lone pair build-up on both C and S, consistent with the strongly non-linear angles about these two atoms. The authors conclude that 3 is a “structure with a rather strong CS double bond or a weak triple bond”.

References

(1) Schreiner, P. R.; Reisenauer, H. P.; Romanski, J.; Mloston, G., "A Formal Carbon-Sulfur Triple Bond: H-C≡S-O-H," Angew. Chem. Int. Ed., 2009, 48, 8133-8136, DOI: 10.1002/anie.200903969

A computational study of addition of singlet carbenes to bicyclobutanes reveals another potential energy surface where dynamics may be active. Rablen, Jones and co-workers examined the reaction of dichlorocarbene with bicyclobutane 1 and 1,2,2-trimethylbicyclobutane 2 (Reactions 1 and 2) using a number of computational techniques.¹

For reaction 1, they identified three reaction pathways. The first two involve the carbene approaching along the central C-C bond. Path A (Scheme 1) involves a single transition state that leads to product 3, with a barrier of 8.4 kcal mol^-1. The second pat (pathway B), leads to critical point 4, which is a transition state at HF/6-31G* and QCISD/6-31G* but is a local minimum at CCSD/6-31G*. This minimum however is very shallow, and vibrational energy will exceed the barriers about it. Both pathways indicate an asynchronous but concerted reaction. The last pathway (C) is for insertion of the carbine into the bridgehead C-C bond, leading to the bicyclo product 5. This barrier is very high, 27 kcal mol^-1, and so this path is unlikely to be competitive.

Experimental study of Reaction 2 showed that only 6 is produced.² Rablen and Jones identified six pathways where the carbene attacks 2 along the bridgehead bond (analogous to Paths A and B, except there are three rotamers and the attack can be at either bridgehead carbon) and the insertion path that leads to 8. Once again, this last pathway has a very large barrier and is non-competitive. Attack at the unsubstituted bridgehead carbons is favored over attack at the methyl-substituted bridgehead by 2-3 kcal mol^-1. The path that leads directly to 7 has a slightly lower barrier (0.4 kcal mol^-1) than the path that leads directly to 8. The analog of Path B leads here to a true intermediate 9 through a barrier 0.4 kcal mol^-1 higher than the barrier that leads to 7. This intermediate is shown in Figure 1.

Figure 1. CCSD/6-31G* structure of intermediate 9.¹

The energies of the barriers suggest that 7 will be the major product, but not the exclusive product. Rablen and Jones point out that intermediate 9 lies in a very shallow plateau and exit from this intermediate can lead to either 7 or 8. This sort of potential energy surface has been implicated in reactions that exhibit non-statistical behavior indicative of dynamic effects (see Chapter 7 of my book). Rablen and Jones speculate that dynamics might be dictating the product distribution in Reaction 2 as well. Confirmation awaits a molecular dynamics study.

References

(1) Rablen, P. R.; Paiz, A. A.; Thuronyi, B. W.; Jones, M., "Computational Investigation of the Mechanism of Addition of Singlet Carbenes to Bicyclobutanes," J. Org. Chem. 2009, DOI: 10.1021/jo900485z

(2) Jackson, J. E.; Mock, G. B.; Tetef, M. L.; Zheng, G.-x.; Jones, M., "Reactions of carbenes with bicyclobutanes and quadricyclane : Cycloadditions with two σ bonds," Tetrahedron 1985, 41, 1453-1464, DOI: 10.1016/S0040-4020(01)96386-0.

InChIs

1: InChI=1/C4H6/c1-3-2-4(1)3/h3-4H,1-2H2
InChIKey=LASLVGACQUUOEB-UHFFFAOYAV

2: InChI=1/C7H12/c1-6(2)5-4-7(5,6)3/h5H,4H2,1-3H3
InChIKey=GJMVYBBYZUWWLJ-UHFFFAOYAI

3: InChI=1/C5H6Cl2/c1-2-3-4-5(6)7/h2,4H,1,3H2
InChIKey=FGUOQAVVVDPABB-UHFFFAOYAR

5: InChI=1/C5H6Cl2/c6-5(7)3-1-4(5)2-3/h3-4H,1-2H2
InChIKey=SUZACPSWEYRCBD-UHFFFAOYAW

6: InChI=1/C8H12Cl2/c1-6(2)8(3,4)5-7(9)10/h5H,1H2,2-4H3
InChIKey=QIFFCMZJZYIIBA-UHFFFAOYAZ

7: InChI=1/C8H12Cl2/c1-6(2)7(3)4-5-8(9)10/h5H,4H2,1-3H3
InChIKey=MOELQSRRCNAPQV-UHFFFAOYAX

8: InChI=1/C8H12Cl2/c1-6(2)5-4-7(6,3)8(5,9)10/h5H,4H2,1-3H3
InChIKey=PRCOWYZGJRWGOB-UHFFFAOYAP

Following on the great study of hydroxycarbene¹ (see my blog post), Schreiner now reports on the synthesis and characterization of dihydroxycarbene 1.² It is prepared by high-vacuum flash pyrolysis of oxalic acid (Scheme 1).

Scheme 1

Dihydroxycarbene can exist in three different conformations characterized by the relationship about the C-O bond, either s-cis or s-trans. The three conformations are shown in Figure 1, and the s-trans,s-trans structure is the local energy minimum (computed at CCSD(T)/cc-pVTZ).

1tt (0.0)

1ct (0.1)

1cc (6.7)

Figure 1. CCSD(T)/cc-pVTZ optimized geometries and relative energies (kcal mol^-1) of the conformers of 1.²

Identification of the 1 is made through comparison of the experimental and computed IR vibrational frequencies. As an example, the experimental and computed frequencies for the s-trans,s-trans conformer are listed in Table 1. The agreement is excellent.

Table 1. Computed and experimental vibrational frequencies (cm^-1) and intensities (in parentheses) of the s-trans,s-trans conformation of 1.²

Unlike hydroxycarbene, dihydroxycarbene is stable. The amazing instability of hydroxycarbene is due to tunneling through a large barrier: nearly 30 kcal mol^-1.¹ The tunneling route for the decomposition of 1 is more difficult for two reasons. First, its C-O bond is quite strong; the C-O distance is quite short, 1.325 Å. This makes a long distance that must be traversed in the tunneling mode. (The strong bond is due to π-donation from the oxygen lone pair into the empty carbon p orbital; this is noted by the large rotational barrier about the C-O bonds of 17 kcal mol^-1!) Second, the activation barrier for decomposition is very high, at least 34 kcal mol^-1.

References

(1) Schreiner, P. R.; Reisenauer, H. P.; Pickard Iv, F. C.; Simmonett, A. C.; Allen, W. D.; Matyus, E.; Csaszar, A. G., "Capture of hydroxymethylene and its fast disappearance through tunnelling," Nature, 2008, 453, 906-909, DOI: 10.1038/nature07010.

(2) Schreiner, P. R.; Reisenauer, H. P., "Spectroscopic Identification of Dihydroxycarbene13," Angew. Chem. Int. Ed., 2008, 47, 7071-7074, DOI: 10.1002/anie.200802105

InChIs

1: InChI=1/CH2O2/c2-1-3/h2-3H