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

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!

Houk has performed a very nice examination of the performance of some density functionals.¹ He takes a quite different approach than what was proposed by Grimme – the “mindless” benchmarking² using random molecules (see this post). Rather, Houk examined a series of simple aldol, Mannich and α-aminoxylation reactions, comparing their reaction energies predicted with DFT against that predicted with CBQ-QB3. The idea here is to benchmark DFT performance for simple reactions of specific interest to organic chemists. These reactions are of notable current interest due their involvement in organocatalytic enantioselective chemistry (see my posts on the aldol, Mannich, and Hajos-Parrish-Eder-Sauer-Wiechert reaction). Examples of the reactions studied (along with their enthalpies at CBS-QB3) are Reaction 1-3.

For the four simple aldol reactions and four simple Mannich reactions, PBE1PBE,
mPW1PW91 and MO6-2X all provided reaction enthalpies with errors of about 2 kcal mol^-1. The much maligned B3LYP functional, along with B3PW91 and B1B95 gave energies with significant larger errors. For the three α-aminoxylation reactions, the errors were better with B3PW91 and B1B95 than with PBE1PBE or MO6-2X. Once again, it appears that one is faced with finding the right functional for the reaction under consideration!

Of particular interest is the decomposition of these reactions into related isogyric, isodesmic
and homdesmic reactions. So for example Reaction 1 can be decomposed into Reactions 4-7 as shown in Scheme 1. (The careful reader might note that these decomposition reactions are isodesmic and homodesmotic and hyperhomodesmotic reactions.) The errors for Reactions 4-7 are typically greater than 4 kcal mol^-1 using B3LYP or B3PW91, and even with MO6-2X the errors are about 2 kcal mol^-1.

Scheme 1.

Houk also points out that Reactions 4, 8 and 9 (Scheme 2) focus on having similar bond changes as in Reactions 1-3. And it’s here that the results are most disappointing. The errors produced by all of the functionals for Reactions 4,8 and 9 are typically greater than 2 kcal mol^-1, and even MO2-6x can be in error by as much as 5 kcal mol^-1. It appears that the reasonable performance of the density functionals for the “real world” aldol and Mannich reactions relies on fortuitous cancellation of errors in the underlying reactions. Houk calls for the development of new functionals designed to deal with fundamental simple bond changing reactions, like the ones in Scheme 2.

Scheme 2

References

(1) Wheeler, S. E.; Moran, A.; Pieniazek, S. N.; Houk, K. N., "Accurate Reaction Enthalpies and Sources of Error in DFT Thermochemistry for Aldol, Mannich, and α-Aminoxylation Reactions," J. Phys. Chem. A 2009, 113, 10376-10384, DOI: 10.1021/jp9058565

(2) Korth, M.; Grimme, S., ""Mindless" DFT Benchmarking," J. Chem. Theory Comput. 2009, 5, 993–1003, DOI: 10.1021/ct800511q

Coming on the heels of the very nice combined computational/experimental study of the enantioselective Strecker reaction by Jacobsen (see this post), there’s this JACS communication that really disappoints in its use of computational chemistry. Cobb uses yet another chiral thiourea to produce the enantioselective intramolecular Michael addition of nitronoates (Reaction1).¹ The reaction goes with excellent diastereoselectivity and eneatioselectivity, and can even be done with a substrate to produce three chiral centers. This is very nice synthetic chemistry.

The lack of reactivity of the Z ester suggested that the thiourea must associate with both the nitro group and the ester carbonyl. The authors provide a B3LYP/3-21G complex of thiourea with a simple nitroester (once again without providing coordinates in the supporting materials!) to demonstrate this sort of association. But this single structure, at this very low computational level, with these simplified reagents, and lacking solvent (see Rzepa’s comment) really makes one wonder just what value this computation provides. It also goes to demonstrate just how much effort Jacobsen went through to provide substantive computational support for his proposed mechanism of action.

References

(1) Nodes, W. J.; Nutt, D. R.; Chippindale, A. M.; Cobb, A. J. A., "Enantioselective Intramolecular Michael Addition of Nitronates onto Conjugated Esters: Access to Cyclic γ-Amino Acids with up to Three Stereocenters," J. Am. Chem. Soc. 2009, 131, 16016-16017, DOI: 10.1021/ja9070915

The competition between Bergman cyclization and Myers-Saito cyclization of ene-ynes and related species is discussed in Chapter 3.3 of my book and also in these posts. Yet another variation, the Garratt-Braverman cyclization^1-3 has now been examined in terms of competition with the Myers-Saito cyclization for 1 using both experiments and computations.⁴ Subjecting 1 to base should cause the rearrangement to either GB1 or MS2. These can undergo either the Garratt-Braverman cyclization to give GB2 or the Myers-Saito cyclization to MS2.

B3LYP/6-31G(d) predicts that GB1 is only slightly higher in energy than MS1 (by 0.7 kcal mol^-1). The transition states (GB1toGB2 or MS1toMS2 – see Figure 1) each lie 24.4 kcal mol^-1 above their respective reactants. However, the diradical GB2 is 7.2 kcal mol^-1 below GB1 but MS2 is only 0.3 kcal mol^-1 below MS1. So while the two reactions are of similar kinetic probability, having identical activation barriers, the GB route leads to the more thermodynamically stable intermediate. Furthermore, the GB route ultimately results in GBP, via an intramolecular cyclization of the diradical, while the MS route, which ends with MSP, requires intermolecular abstraction of 4 hydrogens. Thus, the unimolecularity of the GB path further favors the GB route over the MS pathway. In fact, experimental studies of 1 and related compounds all give rise to the GB product only.

GB1	GB1toGB2
GB2
MS1	MS1toMS2
MS2

Figure 1. B3LYP/6-31G(d) optimized structures.⁴

References

(1) Braverman, S.; Segev, D., "Novel cyclization of diallenic sulfones," J. Am. Chem. Soc. 2002, 96, 1245-1247, DOI: 10.1021/ja00811a060

(2) Garratt, P. J.; Neoh, S. B., "Strained heterocycles. Properties of five-membered heterocycles fused to four-, six-, and eight-membered rings prepared by base-catalyzed rearrangement of 4-heterohepta-1,6-diynes," J. Org. Chem. 2002, 44, 2667-2674, DOI: 10.1021/jo01329a016

(3) Zafrani, Y.; Gottlieb, H. E.; Sprecher, M.; Braverman, S., "Sequential Intermediates in the Base-Catalyzed Conversion of Bis(π-conjugated propargyl) Sulfones to 1,3-Dihydrobenzo- and Naphtho[c]thiophene-2,2-dioxides," J. Org. Chem. 2005, 70, 10166-10168, DOI: 10.1021/jo051692i

(4) Basak, A.; Das, S.; Mallick, D.; Jemmis, E. D., "Which One Is Preferred: Myers-Saito Cyclization of Ene-Yne-Allene or Garratt-Braverman Cyclization of Conjugated Bisallenic Sulfone? A Theoretical and Experimental Study," J. Am. Chem. Soc. 2009, 131, 15695-15704, DOI: 10.1021/ja9023644

Jacobsen has been pioneering the use of small organic molecules as catalysts where the interaction between the substrate and catalyst is non-covalent. At the 2009 Welch Conference last week, he spoke about the use of amido-thiourea catalysts in the enantioselective Strecker reaction. This post discusses how computations were used to determine the mechanism and helps explain the enantioselectivity.

The thiourea 1 was found to be the best catalyst for the hydrocyanation of imines. An example of this catalysis is Reaction 1. The system is quite tolerant to changes of the group attached to the carbon of the imine: with R = t-butyl group, the yield is 99% with an enantiomeric excess of 93% and with a phenyl group, the yield is 98% with 98% ee.¹

In a follow-up article, Jacobsen employs a nice combination of experiments and DFT computations to shed light on the mechanism.² Kinetic studies established that the rate of the hydrocyanation is first order in HCN, imine and catalyst. This suggested two possible mechanisms, Scheme 1a (where protonation of the imine is followed by formation of the C-CN bond) and Scheme 1b (where cyanide adds first, followed by protonation).

Scheme 1.

A Hammett study of phenyl-substituted imines indicates a negative ρ value, indicative of positive charge build up on nitrogen, suggesting the mechanism shown in Scheme 1a. Now on the computations!

A model study was first performed at B3LYP/6-31G(d) for the reaction of HCN with imine 2a with the catalyst 3a. Three complexes involving the three species of nearly equivalent energy were found. The first mechanism examined is for direct addition of cyanide to imine with the catalyst activating the imine. This pathway was identified but it has a very high barrier (46 kcal mol^-1) and the rates of the urea and thiourea-catalyzed reactions are nearly identical, but the computations for this mechanism suggest that the thiourea-catalyzed reaction should be substantially faster. This mechanism can be discounted.

Next, they examined two related mechanism whereby either HCN or HNC complex to the catalysts and then transfer their proton to the imine. This is followed by cyanide attack on the protonated imine. The reaction involving HNC is slightly lower than that of HCN, and so this mechanism is pursued further with catalyst 3b, which more closely mimics the true catalyst, and imine 2b. The lowest energy pathway for the addition of HCN to 2b with catalyst 3b is schematically shown in Scheme 2. From A to E is transfer of the proton from HNC to the imine and rotation of the CN anion. The highest barrier is through TS F, which involves moving the imine over to the carbonyl group. The last step is the attack of the cyanide group. The structures of E through I are shown in Figure 1.

Scheme 2

E	F
G	H
I

Figure 1. B3LYP/6-31G(d) optimized geometries for steps along Scheme 2.

The step involving the transition state F is rate determining. They then computed the difference in the activation barrier through TS F for a variety of different imines using the R– and S-catalyst and compared that with the experimental enantioselectivity. These turn out to correlate extremely well, suggesting that in fact the enantioselectivity is discriminated through TS F! And the structural feature that best correlates with this enantioselectivty is the sum of the O^…H and N^…H distances in F for the R– and S-catalysts. So it is the ability to stabilize the iminium cation that is key.

A couple of caveats: first, the potential energy surface of this reaction is quite complex – Jacobsen suggests a pathway with 9 critical points. One might imagine that there could be other pathways and other important critical points, and fully characterizing this surface would be an enormous task! The nice agreement between the computations and the available experiments do give the computed pathway some credence. Second, the reactions are run in solution, and solvent has been neglected in these computations. Given that charge-separated species are being formed, solvent could be a factor. Nonetheless, this remains an interesting set of papers as it shows how computations are now a standard tool even amongst synthetic chemists!

References

(1) Zuend, S. J.; Coughlin, M. P.; Lalonde, M. P.; Jacobsen, E. N., "Scaleable catalytic asymmetric Strecker syntheses of unnatural α-amino acids," Nature, 2009, 461, 968-970, DOI: 10.1038/nature08484.

(2) Zuend, S. J.; Jacobsen, E. N., "Mechanism of Amido-Thiourea Catalyzed Enantioselective Imine Hydrocyanation: Transition State Stabilization via Multiple Non-Covalent Interactions," J. Am. Chem. Soc. 2009, 131, 15358-15374, DOI: 10.1021/ja9058958.

Torquoselectivity rules (discussed in Chapter 3.5 of my book) indicate that 3-phenylcyclobutene will ring-open to give the outward rotated product (Reaction 1). Houk and Tang report a seeming contradiction, namely the ring opening of 1 gives only the inward product 3 (Reaction 2).¹

B3LYP/6-31G* computations on the ring-opening of 4 indicate that the activation barrier for the outward path (leading to 5) is nearly 8 kcal mol^-1 lower than the barrier for the inward path (leading to 6, see Reaction 3). This is consistent with torquoselectivity rules, but what is going on in the experiment?

In the investigation of the isomerization of the outward to inward pathway, they discovered a low-energy pyran intermediate 7. This led to the proposal of the mechanism shown in Reaction 3. The highest barrier is for the electrocyclization that leads to the outward product 5. The subsequent barriers – the closing to the pyran 7 and then the torquoselective ring opening to 6 –  are about than 13 kcal mol^-1 lower in energy than for the first step. The observed product is the thermodynamic sink. And the nice thing about this mechanism is that torquoselection is preserved.

References

(1) Um, J. M.; Xu, H.; Houk, K. N.; Tang, W., "Thermodynamic Control of the Electrocyclic
Ring Opening of Cyclobutenes: C=X Substituents at C-3 Mask the Kinetic Torquoselectivity," J. Am. Chem. Soc. 2009, 131, 6664-6665, DOI: 10.1021/ja9016446.

InChIs

4: InChI=1/C16H16O6/c1-20-13(17)11-9-16(14(18)21-2,15(19)22-3)12(11)10-7-5-4-6-8-10/h4-9,12H,1-3H3
InChIKey=VBOGEHVOAGDMNG-UHFFFAOYAR

5: InChI=1/C16H16O6/c1-20-14(17)12(9-11-7-5-4-6-8-11)10-13(15(18)21-2)16(19)22-3/h4-10H,1-3H3/b12-9-
InChIKey=PZRWKBUUAFMPBC-XFXZXTDPBF

6: InChI=1/C16H16O6/c1-20-14(17)12(9-11-7-5-4-6-8-11)10-13(15(18)21-2)16(19)22-3/h4-10H,1-3H3/b12-9+
InChIKey=PZRWKBUUAFMPBC-FMIVXFBMBS

7: InChI=1/C16H16O6/c1-19-14(17)11-9-12(15(18)20-2)16(21-3)22-13(11)10-7-5-4-6-8-10/h4-9,13H,1-3H3/t13-/m0/s1
InChIKey=QSJZITDSTPMCEM-ZDUSSCGKBG

Can one steer the course of a reaction by selectively applying a force to a molecule? Atomic force microscopy opens up this avenue. Martinez¹ has just published a computational study on the ring opening of cyclobutene with applied forces. Cyclobutene should ring-open in a conrotatory fashion according to the Woodward-Hoffman rules. But Martinez shows that by pulling on cyclobutene in a cis fashion, the disrotatory pathway can become the more favored route. Thus, it appears that mechanochemistry might be an alternative way to create selectivity in chemical reactions!

References

(1) Ong, M. T.; Leiding, J.; Tao, H.; Virshup, A. M.; Martinez, T. J., “First Principles Dynamics and Minimum Energy Pathways for Mechanochemical Ring Opening of Cyclobutene,” J. Am. Chem. Soc., 2009, 131, 6377-6379, DOI: 10.1021/ja8095834.

InChIs

cyclobutene: InChI=1/C4H6/c1-2-4-3-1/h1-2H,3-4H2
InChIKey: CFBGXYDUODCMNS-UHFFFAOYAN

Houk¹ examined the Mannich reaction of the enamine formed from acetone and S-proline with N-ethylidine-N-phenylamine (see Chapter 5.3.3 in my book). Parasuk and Parasuk now extend this to the reaction of the enamine of cyclohexanone and S-proline with N-phenylmethanimine (Reaction 1).² Geometries were optimized at B3LYP/6-31++G(d,p) and single-point energies computed with PCM (for the solvent DMSO) at both B3LYP and MP2.

Reaction 1

First, they examined the formation of the enamine 1, which can be in the syn or anti conformation. The barrier for formation of the syn isomer is 10.2 kcal mol^-1. The barrier for the formation of the anti conformer is much higher, 17.9 kcal mol^-1, and this is with a single water molecule used to assist the proton migration. However, the rotational barrier between the two conformers is only 4.2 kcal mol^-1. So, they conclude that the syn isomer is the only conformer directly formed by the reaction of cyclohexanone and S-proline, and then rotation can produce the anti conformer.

The located the transition state for the reaction of either syn–1 or anti–1 with phenylmethanimine. The two transition states are shown in Figure 1. The barrier for the reaction of syn–1 is 8.5 kcal mol^-1, leading to the S product. The other barrier is higher, 13.0 kcal mol^-1, and the R product 2R is 6.8 kcal mol^-1 higher in energy than the S product 2S. Thus, the reaction to give the S product is both kinetically and thermodynamically favored. This is consistent with experiment³ which gives the S product with 99%ee. Inclusion of solvent makes the S product even more thermodynamically and kinetically favored over the R isomer.

TS-2S

TS-2R

Figure 1. B3LYP/6-311++G(d,p) optimized transition states leading to 2S and 2R.²

References

(1) Bahmanyar, S.; Houk, K. N., "Origins of Opposite Absolute Stereoselectivities in Proline-Catalyzed Direct Mannich and Aldol Reactions," Org. Lett. 2003, 5, 1249-1251, DOI: 10.1021/ol034198e.

(2) Parasuk, W.; Parasuk, V., "Theoretical Investigations on the Stereoselectivity of the Proline Catalyzed Mannich Reaction in DMSO," J. Org. Chem. 2008, 73, 9388-9392, DOI: 10.1021/jo801872w.

(3) Ibrahem, I.; Zou, W.; Casas, J.; Sundén, H.; Córdova, A., "Direct organocatalytic enantioselective α-aminomethylation of ketones," Tetrahedron 2006, 62, 357-364, DOI: 10.1016/j.tet.2005.08.113.

InChIs

1: InChI=1/C11H17NO2/c13-11(14)10-7-4-8-12(10)9-5-2-1-3-6-9/h5,10H,1-4,6-8H2,(H,13,14)/t10-/m0/s1/f/h13
InChIKey=FGOQJKISPWOYSX-WSLRCUSADU

2S: InChI=1/C18H24N2O2/c21-18(22)16-10-6-11-17(16)20-12-5-4-9-15(20)13-19-14-7-2-1-3-8-14/h1-3,7-8,15-16,19H,4-6,9-13H2/b20-17+/t15-,16+/m0/s1
InChIKey=SDMHQUCIHUXJMJ-OQSOEKIEBW

2R: InChI=1/C18H24N2O2/c21-18(22)16-10-6-11-17(16)20-12-5-4-9-15(20)13-19-14-7-2-1-3-8-14/h1-3,7-8,15-16,19H,4-6,9-13H2/b20-17-/t15-,16-/m1/s1
InChIKey=SDMHQUCIHUXJMJ-HGWRPWPUBS

Sheppard and Acevedo¹ have reported a careful re-examination of the ene reaction of singlet oxygen with alkenes that points out inherent difficulties in examining high-dimension potential energy surfaces by reducing the dimensionality.

Their work begins by careful reassessment of the computational study of Singleton, Foote and Houk.² These authors looked at the reaction of singlet oxygen with cis-2-butene by creating a 15×15 gird of optimized geometries holding the C-O distance fixed to specific values while letting the other geometric variables completely relax (see 1). These geometries were obtained at B3LYP/6-31G* and single-point energies were then obtained at CCSD(T)/6-31G*. They find two transiti0n states, one corresponding to symmetric addition of oxygen to the alkene 2 which leads to the pereperoxide 3. However, this pereperoxide 3 is not an intermediate, but rather a transition state for interconversion of the ene products 4 and 5. These structures and mechanism appear consistent with the experimental kinetic isotope effects. The authors characterize the reaction as “two-step no-intermediate”. Essentially, the reactants would cross the first transition state 1, encounter a valley-ridge inflection point that bifurcates reaction paths that go to either 3 or 4 and avoid ever reaching the second transition state 2.

Sheppard and Acevedo¹ tackle two major issues with this work. First, they are concerned about the role of solvent and so perform QM/MM computations with either DMSO, water of cyclohexane as solvent. The second factor is the choice of scanning just a 2-D grid as a projection of the multidimensional potential energy surface. Sheppard and Acevedo point out that since all other variable are optimized in this process, the hydrogen atom that is involved in the ene process must be bonded to either C or O and is therefore removed from the reaction coordinate. So they have performed a 3-D grid search where in addition to the two C-O distances they use the O-C-C angle as a variable. They find that this PES provides the more traditional stepwise pathway: a transition state that leads to formation of the pereperoxide intermediate and then a second transition state that leads to the ene product. In addition, solvent effects are significant, a not unexpected result given the large dipole of the pereperoxide.

But the main point here is that one must be very careful in reducing the dimensionality of the hypersurface and drawing conclusions from this reduced surface. It appears that the valley-ridge inflection point in the single oxygen ene reaction is an artifact of just this reduced dimensionality.

References

(1) Sheppard, A. N.; Acevedo, O., “Multidimensional Exploration of Valley-Ridge Inflection Points on Potential-Energy Surfaces,” J. Am. Chem. Soc. 2009, 131, 2530-2540, DOI: 10.1021/ja803879k.

(2) Singleton, D. A.; Hang, C.; Szymanski, M. J.; Meyer, M. P.; Leach, A. G.; Kuwata, K. T.; Chen, J. S.; Greer, A.; Foote, C. S.; Houk, K. N., “Mechanism of Ene Reactions of Singlet Oxygen. A Two-Step No-Intermediate Mechanism,” J. Am. Chem. Soc. 2003, 125, 1319-1328, DOI: 10.1021/ja027225p.

InChIs

Pereperoxide: InChI=1/C4H9O2/c1-3-4(2)6(3)5/h3-5H,1-2H3/t3-,4+
InChIKey=FRFPREFIPHRMOI-ZXZARUISBV

3: InChI=1/C4H8O2/c1-3-4(2)6-5/h3-5H,1H2,2H3/t4-/m1/s1
InChIKey=KRKIWMRTOODQMQ-SCSAIBSYBR

4: InChI=1/C4H8O2/c1-3-4(2)6-5/h3-5H,1H2,2H3/t4-/m0/s1
InChIKey=KRKIWMRTOODQMQ-BYPYZUCNBC