Synthetic application of the Bergman cyclization is rare. Basak reports a real interesting use of this reaction to create polycyclic aromatics.¹ So, for example, heating up 1 in DMSO leads to the 4helicene 2. The proposed mechanism is shown in Figure 1. The Bergman cyclization leads to the biradical 3, which adds to the pendant phenyl group to give 4. Hydrogen abstraction then gives 5, which abstracts hydrogens from the solvent to produce 6. (Use of DMSO-d ₆ provides deuterium incorporated products consistent with the diradical shown in 4.) Oxidation then gives the final product 2.

Figure 1. Proposed mechanism for the conversion of 1 to 2.

B3LYP computations were performed to examine the relative rates with substituents on the phenyl ring. The structure of 1’ (with a methyl group replacing the Ns group – 4-nitrobenzenesulfonyl) and the transition state for the Bergman cyclization are shown in Figure 2. Unfortunately, computations were not used to analyze the complete proposed mechanism – a project that awaits the eager student perhaps?

1’

1’TS

Figure 2. B3LYP/def2-TZVP//BP86/def2-TZVP optimized structures of 1’ and transition state for the Bergman cyclization of 1’.

References

(1) Roy, S.; Anoop, A.; Biradha, K.; Basak, A., "Synthesis of Angularly Fused Aromatic Compounds from Alkenyl Enediynes by a Tandem Radical Cyclization Process," Angew. Chem. Int. Ed., 2011, 50, 8316-8319, DOI: 10.1002/anie.201103318

InChIs

1’: InChI=1/C21H17N/c1-22-15-7-12-20-10-5-6-11-21(20)14-13-19(17-22)16-18-8-3-2-4-9-18/h2-6,8-11,16H,15,17H2,1H3/b19-16+
InChIKey=MKFCCTRNSOHUDU-KNTRCKAVBS

2’: InChI=1/C21H17N/c1-22-12-16-10-14-6-2-4-8-18(14)21-19-9-5-3-7-15(19)11-17(13-22)20(16)21/h2-11H,12-13H2,1H3
InChIKey=ZNCMIYYKBITIMW-UHFFFAOYAR

In a follow-up to their experimental study that found that cyclobutenone is an excellent dienophile (and which I blogged about here), Danishefsky teams up with Houk and provides an insight into the reactivity.¹ In the Diels-Alder reaction of cyclopentadiene with 2-cyclohexenone, 2-cyclopentenone and cyclobutenone, the product yield increases in the order 36%, 50% and 77%. M06-2x activation enthalpies decrease in this series 15.0, 13.3 and 10.5 kcal mol^-1.

While these activation energies do not correlate with reaction energies, the activation energies do correlate nicely with the distortion energy. (Distortion energy is the energy required to distort reactants to their geometries in the transition state, but without their interaction.) Houk and Danishefsky argue that it is much easier to distort cyclobutenone to its geometry in the TS (and this distortion is primarily moving the alkenyl hydrogens out of plane, away from the incoming diene) than for the larger rings. This is due to (a) the larger s-character of the C-H bond in the smaller ring and (b) the C-C-C angle in the smaller ring is closer to the angle in the pyramidalized TS structure.

References

(1) Paton, R. S.; Kim, S.; Ross, A. G.; Danishefsky, S. J.; Houk, K. N., "Experimental Diels–Alder Reactivities of Cycloalkenones and Cyclic Dienes Explained through Transition-State Distortion Energies," Angew. Chem. Int. Ed., 2011, 44, 10366–10368, DOI: 10.1002/anie.201103998

Reactions whose outcomes depend on dynamic processes is a major theme of my book and this blog. The recent study of the reaction of a nucleophile (hydroxide) with bromoacetophenones adds yet another case for post-transition state product determination.

Itoh and Yamataka have examined the reaction of hydroxide with substitutes α-bromoacetophenones 1.¹ The nucleophile can attack at the carbonyl carbon or the α-carbon, though both lead ultimately to the same product, as shown in Scheme 1.

Scheme 1

B3LYP/6-31+G* computations of the reaction surface with a variety of different substituents on the phenyl ring of 1 located in all cases a single transition state for the two different reactions (addition and substitution). This TS is shown in Figure 1 for the parent case (X=H).

Figure 1. The single transition state for the addition and substitution reaction of 1 and hydroxide.

Tracing the IRC forward leads to either the carbonyl addition product or the substitution product, and which path is traced depends to some extent on the nature of the substituent. Most intriguing is that trajectories initiated at the transition state lead to both products. So once again, we see a case where a single transition state leads to two products, and product selectivity is determine by the dynamics – the initial conditions at the TS dictate which of the two products is eventually obtained.

References

(1) Itoh, S.; Yoshimura, N.; Sato, M.; Yamataka, H., "Computational Study on the Reaction Pathway of α-Bromoacetophenones with Hydroxide Ion: Possible Path Bifurcation in the Addition/Substitution Mechanism," J. Org. Chem., 2011, 70, 8294–8299, DOI: 10.1021/jo201485y

Bendikov and co-workers have examined the dimerization of linear acenes at M06-2x/6-31G(d).¹ They have looked at the formal forbidden [4+4] reaction that takes, for example, 2 molecules of benzene into three possible dimer products 1P_anti1-2, 1P_syn1-2, and 1P_syn1-4. The relative energies of these products increases in that order, and all three are much higher in energy than reactants; the lowest energy dimer is 1P_anti1-2, lying 47.4 kcal mol^-1 above two benzene molecules. Similarly, the dimerization of naphthalene is also endothermic, but the formation of the symmetric dimer of anthracene 3P-2,2’ is exothermic by 5.4 kcal mol^-1. This gibes nicely with the best estimate of -9 ± 3 kcal mol^-1.² Dimerization of the higher acenes are increasingly exothermic.

The transition state for the dimerization of benzene is concerted, though very asymmetric, as seen in Figure 1. Its energy is quite high (77.79 kcal mol^-1) and so this reaction can be completely discounted. The TS for the dimerization of naphthalene is also concerted and asymmetric, but the reaction pathway for the dimerization is stepwise, with a diradical intermediate. Furthermore, the highest barrier for this stepwise reaction is 33.3 kcal mol^-1. The activation energy of the back reaction (anthracene dimer to two anthrecene molecules) was measured 36.3 kcal mol^-1,³ and the computed barrier of 38.7 kcal mol^-1 is in nice agreement. The computed barriers for the dimerization of the higher acenes are predicted to be even lower than that of anthracene, consistent with the observation of dimers of these molecules.

1Panti1-2	1TSanti1-2
1P-42	1TS-42

Figure 1. M06-2x /6-31G(d) optimized structures.

I was curious that the authors did not consider the formally allowed [4+2] dimerization, leading for example to 1P-42. So, I optimized this product and the concerted transition state leading to it. These are shown in Figure 1. The barrier through this transition state is still very large (54.1 kcal mol^-1) but it is 23 kcal mol^-1 lower in energy than the barrier of the [4+4] reaction! The Product of the [4+2] is also lower in energy (by 9 kcal mol^-1) than 1P_anti1-2. It seems to me that this type of dimerization is worth examining too – though I must say I have not as yet looked to see if anyone has explored this already.

References

(1) Zade, S. S.; Zamoshchik, N.; Reddy, A. R.; Fridman-Marueli, G.; Sheberla, D.; Bendikov,
M., "Products and Mechanism of Acene Dimerization. A Computational Study," J. Am. Chem. Soc., 2011, 133, 10803-10816, DOI: 10.1021/ja106594v

(2) Grimme, S.; Diedrich, C.; Korth, M., "The Importance of Inter- and Intramolecular van der Waals Interactions in Organic Reactions: the Dimerization of Anthracene Revisited," Angew. Chem. Int. Ed., 2006, 45, 625-629, DOI: 10.1002/anie.200502440

(3) Greene, F. D., "Problems of stereochemistry in photochemical reactions in the anthracene area," Bull. Soc. Chim. Fr., 1960, 1356-1360

InChIs

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

1P_anti1-2: InChI=1/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H
InChIKey=WMPWOGVJEXSFLI-UHFFFAOYAP

1P_syn1-2: InChI=1/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H
InChIKey=WMPWOGVJEXSFLI-UHFFFAOYAP

1P_syn1-4: InChI=1/C12H12/c1-2-10-4-3-9(1)11-5-7-12(10)8-6-11/h1-12H
InChIKey=BCBHEUOKKNYIAT-UHFFFAOYAI

1P-42: InChI=1/C12H12/c1-2-4-12-10-7-5-9(6-8-10)11(12)3-1/h1-12H
InChIKey=ONVDJSCNMCYFTI-UHFFFAOYAY

Anthracene: InChI=1/C14H10/c1-2-6-12-10-14-8-4-3-7-13(14)9-11(12)5-1/h1-10H
InChIKey=MWPLVEDNUUSJAV-UHFFFAOYAK

3P-2,2’: InChI=1/C28H20/c1-2-10-18-17(9-1)25-19-11-3-4-12-20(19)26(18)28-23-15-7-5-13-21(23)27(25)22-14-6-8-16-24(22)28/h1-16,25-28H
InChIKey=JUTIJVADGQDBGY-UHFFFAOYAY

We have all learned about aromatic substitution as proceeding via the following mechanism

(Worse yet – many of us have taught this for years!) Well, Galabov, Zou, Schaefer and Schleyer pour a whole lot of cold water on this notion in their recent Angewandte article.¹ Modeling the reaction of benzene with Br₂ and using B3LYP/6-311+G(2d,2p) for both the gas phase and PCM simulating a CCl₄ solvent, attempts to locate this standard intermediate led instead to a concerted substitution transition state TS1 (see Figure 1).

TS1

Figure 1. PCM/B3LYP/6-311+G(2d,2p) optimized transitin state along the concerted pathway

However, this is not the lowest energy pathway for substitution. Rather and addition-elimination pathway is kinetically preferred. In the first step Br₂ adds in either a 1,2 or 1,4 fashion to form an intermediate. The lower energy path is the 1,4 addition, leading to P3. This intermediate then undergoes a syn,anti-isomerization to give P5. The last step is the elimination of HBr from P5 to give the product, bromobenzene. This mechanism is shown in Scheme 2 and the critical points are shown in Figure 3.

Scheme 1

TS3	P3
TS6	P5
TS9

Figure 2. PCM/B3LYP/6-311+G(2d,2p) optimized critical points along the addition-elimination pathway

The barrier for the concerted substitution process through TS1 is 41.8 kcal mol^-1 (in CCl₄) while the highest barrier for the addition-elimination process is through TS3 of 39.4 kcal mol^-1.

Now a bit of saving grace is that in polar solvents, acidic solvents and/or with Lewis acid catalysts, the intermediate of the standard textbook mechanism may be competitive.

Textbook authors – please be aware!

References

(1) Kong, J.; Galabov, B.; Koleva, G.; Zou, J.-J.; Schaefer, H. F.; Schleyer, P. v. R., "The Inherent Competition between Addition and Substitution Reactions of Br₂ with Benzene and Arenes," Angew. Chem. Int. Ed. 2011, 50, 6809-6813, DOI: 10.1002/anie.201101852

The click reaction, the copper-assisted cycloaddition of an azide with an alkyne, has been extended to biological systems by use of a strained alkyne (cyclooctyne) thereby eliminating the need of the toxic copper agent.¹ Fox has extended this analogy with the reaction of strained trans-cyclooctene 1 with tetrazine 2.²

The interesting new twist here is to add more strain to trans-cyclooctene to perhaps make the cycloaddition even faster. Bach³ had pointed out that the half chair conformation of 1 is almost 6 kcal mol^-1 higher in energy than the ground state (Figure 1). Fox suggests that fusing a cyclopropyl ring to the eight-member ring would create a ring in the half chair 3. Since 3 would be even more strained than 1, it should undergo a faster cycloaddition reaction.

1	1 (half chair)
3

Figure 1. M06L/6-311+G(d,p) optimized structures of 1 and 3.

Though Fox did not estimate the strain of 3, I have computed the structure of 1 constrained to the geometry of 3, with the two hydrogens that replace the bonds to the cyclopropyl carbon allowed to optimize. This restricted geometry is in fact 6.1 kcal mol^-1 (M06L/6-311+G(d,p)) higher in energy than 1 – so the fusion of the 3-member ring does net the strain increase expected by Bach.

Fox reports estimates of the free energy of activation (at M06L/6-311+G(d,p)) for the reaction of 1or 3 with 2. The barrier for the raction with trans-cyclooctene 1 is 8.92 kcal mol^-1, while the barrier for the reaction with 3 is 6.95 kcal mol^-1. A methylenehydroxyl derivative of 3 was synthesized and it does react 180 times faster than the reaction with 1. Furthermore, the differences in the experimental free energies of activation is 3.0 kcal mol^-1, in excellent agreement with the computed difference.

References

(1) Agard, N. J.; Prescher, J. A.; Bertozzi, C. R., "A Strain-Promoted [3 + 2] Azide-Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems," J. Am. Chem. Soc., 2004, 126, 15046-15047, DOI: 10.1021/ja044996f

(2) Taylor, M. T.; Blackman, M. L.; Dmitrenko, O.; Fox, J. M., "Design and Synthesis of Highly Reactive Dienophiles for the Tetrazine-trans-Cyclooctene Ligation," J. Am. Chem. Soc., 2011, 133, 9646-9649, DOI: 10.1021/ja201844c

(3) Bach, R. D., "Ring Strain Energy in the Cyclooctyl System. The Effect of Strain Energy on [3 + 2] Cycloaddition Reactions with Azides," J. Am. Chem. Soc., 2009, 131, 5233-5243, DOI: 10.1021/ja8094137

InChIs

1: InChI=1/C8H14/c1-2-4-6-8-7-5-3-1/h1-2HInChIKey

2: InChI=1/C12H8N6/c1-3-7-13-9(5-1)11-15-17-12(18-16-11)10-6-2-4-8-14-10/h1-8H
InChIKey=JFBIRMIEJBPDTQ-UHFFFAOYAE

3: InChI=1/C9H14/c1-2-4-6-9-7-8(9)5-3-1/h1-2,8-9H,3-7H2/b2-1+/t8-,9+
InChIKey=YWIJRSGCJZLJNV-YLSDFIPEBO

Matt Seibert pointed out to me a paper of his related to a previous blog post that also deals with the allene-yne thermal [2+2] cyclization. (My apologies to Matt and Dean for overlooking this paper!) Tantillo and Brummond looked at the system with various saturated tethers between these functional groups.¹ For example, UB3LYP/6-31+G(d,p) study of the cyclization of 1 indicates two possible paths, where the 5-member ring is formed first, or where the 7 member ring is formed first. The relative energies of the TSs and intermediates are shown in Figure 1. (Note that there are actually two intermediates on the first pathway, differing in the orientation terminal methyne hydrogen.) The closure to the smaller ring first is favored due to the allylic stabilization of the radical intermediate on this pathway.

Figure 1. Relative energies of TSs and critical point in the cyclization of 1.

Next, they examined the regioselectivity for the inner or outer double bond of the allene in 2. For the reaction with the outer double bond, the 6 member ring is formed first. For the reaction with the inner double bond, the 7-member ring is formed first, and this pathway has a higher barrier than the other. The preference for the reaction with the terminal double bond is consistent with experiments.

Figure 2. Relative energies of TSs and critical point in the cyclization of 2.

With potential diradical intermediates, they decided to append a cyclopropyl ring to as a trap. So, for example, the reaction of 3 can lead to the [2+2] product or to a diradical that might be trapped and identified. The computed energies along these two paths are shown in Figure 3. The activation barrier for the closure to the 2+2 product and for ring opening of the cyclopropyl group are nearly identical, so one might expect to observe both processes. Analogues of 3 were prepared and heated; some evidence of the ring opening of the cyclopropyl group was observed.

Figure 3. Relative energies of TSs and critical point in the cyclization of 3.

References

(1) Siebert, M. R.; Osbourn, J. M.; Brummond, K. M.; Tantillo, D. J., "Differentiating Mechanistic Possibilities for the Thermal, Intramolecular [2 + 2] Cycloaddition of Allene-Ynes," J. Am. Chem. Soc., 2010, 132, 11952-11966, DOI: 10.1021/ja102848z

InChIs

1: InChI=1/C7H8/c1-3-5-7-6-4-2/h1,6H,2,5,7H2
InChIKey=IFOUEVYNVOTODB-UHFFFAOYAI

1P: InChI=1/C7H8/c1-2-6-4-5-7(6)3-1/h2,5H,1,3-4H2
InChIKey=UCCCTNVCSUBFQC-UHFFFAOYAW

2: InChI=1/C8H10/c1-3-5-7-8-6-4-2/h1,6H,2,5,7-8H2
InChIKey=SXDPESVCUVUSMY-UHFFFAOYAU

2Pa: InChI=1/C8H10/c1-2-4-8-6-5-7(8)3-1/h3,6H,1-2,4-5H2
InChIKey=TYATUGPSJUHEJF-UHFFFAOYAU

2Pb: InChI=1/C8H10/c1-6-5-7-3-2-4-8(6)7/h5,8H,1-4H2
InChIKey=MKCUOZNLKWXQFA-UHFFFAOYAC

3: InChI=1/C11H14/c1-2-3-4-5-6-7-8-11-9-10-11/h3,11H,1,4-6,9-10H2
InChIKey=XLOBKJCWEUMVHP-UHFFFAOYAK

3P: InChI=1/C11H14/c1-2-4-10-9(3-1)7-11(10)8-5-6-8/h3,8H,1-2,4-7H2
InChIKey=NLALHZZTFZLGMN-UHFFFAOYAM

Here is a nice example of an interesting synthesis, mechanistic explication using computation (with a bit of an unanswered question), and corroboration of the stereochemistry of the product using computed NMR shifts. Gil and Mischne¹ reacted dimedone 1 with dienal 2 under Knoevenagel conditions to give, presumably, 3. But 3 is not recovered, rather the tricycle 4 is observed.

There are four stereoisomers that can be made (4a-d). Computed ¹³C chemical shifts at OPBE/pcS-1 (this is a basis set suggested for computing chemical shifts²) for these four isomers were then compared with the experimental values. The smallest root mean squared error is found for 4d. Better still, is that these authors utilized the DP4 method of Goodman³ (see this post), which finds that 4d agrees with the experiment with 100% probability!

Lastly, the mechanism for the conversion of 3 to 4 was examined at M06/6-31+G**. The optimized geometries of the starting material, transition state, and product are shown in Figure 1. The free energy barrier is a modest 14.5 kcal mol^-1. The TS indicates a conrotatory 4πe^– electrocyclization. The formation of the C-O bond lags far behind in the TS. They could not identify a second transition state. It would probably be worth examining whether the product of this 4πe^– electrocyclization could be located, perhaps with an IRC starting from the transition state. Does this TS really connect 3 to 4?

3	TS
4

Figure 1. M06/6-31+G** optimized geometries of 3 and 4 and the transition state connecting them.

References

(1) Riveira, M. J.; Gayathri, C.; Navarro-Vazquez, A.; Tsarevsky, N. V.; Gil, R. R.; Mischne, M. P., "Unprecedented stereoselective synthesis of cyclopenta[b]benzofuran derivatives and their characterisation assisted by aligned media NMR and ¹³C chemical shift ab initio predictions," Org. Biomol. Chem., 2011, 9, 3170-3175, DOI: 10.1039/C1OB05109A

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

(3) Smith, S. G.; Goodman, J. M., "Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability," J. Am. Chem. Soc., 2010, 132, 12946-12959, DOI: 10.1021/ja105035r

InChIs

1: InChI=1/C8H12O2/c1-8(2)4-6(9)3-7(10)5-8/h3-5H2,1-2H3
InChIKey=BADXJIPKFRBFOT-UHFFFAOYAX

2: InChI=1/C12H12O/c1-11(10-13)6-5-9-12-7-3-2-4-8-12/h2-10H,1H3/b9-5+,11-6+
InChIKey=VFBDYWDOVMUDEB-MPEOSAONBY

3: InChI=1/C20H22O2/c1-15(8-7-11-16-9-5-4-6-10-16)12-17-18(21)13-20(2,3)14-19(17)22/h4-12H,13-14H2,1-3H3/b11-7+,15-8+
InChIKey=IBEGRISKTNRVOU-YQQAFNMCBC

4d: InChI=1/C20H22O2/c1-19(2)11-15(21)17-16(12-19)22-20(3)10-9-14(18(17)20)13-7-5-4-6-8-13/h4-10,14,18H,11-12H2,1-3H3/t14-,18+,20+/m1/s1
InChIKey=VEGSTZFBNRXEAX-WNYOCNMUBZ

Continuing their studies of ene-yne cyclizations, the Schmittel group examined the apparent [2+2] cyclization of the allene-yne 1.¹ They proposed that it first closed the diradical 2 and then in a second step the four-member ring is formed, giving 3.

Evidence supporting the intermediate diradical is that heating 1a in the presence of 1,4-cyclohexadiene gives 11% of the trapped species 4a. Interestingly, heating 1b gives 26% of 3b, while the reaction of 1c gives 72% of the ring closed product 3c.

Schmittel suggests the intermediate diradical 2b is planar, while 2c is not, and the radical centers are nicely position in the latter compound for quick closure to product.

UBLYP/6-31G(d) computations support the mechanism. The transition state taking 1b to 2b (TS1, shown in Figure 1) lies 20.2 kcal mol^-1 above reactant. The intermediate diradical 2b is 7.9 kcal mol^-1 above reactant 1b. The second transition state (TS2) for closing the four-member ring lies 27.8 kcal mol^-1 above reactant, making it the rate determining step. The overall reaction is exothermic by -12.4 kcal mol^-1. The transition state for a single step reaction, taking 1b directly into 3b (TS3) is very high, 49.0 kcal mol^-1 above 1b, and is therefore non-competitive with the stepwise pathway. These computations suggest a reversible formation of the intermediate, followed by a rate limiting step to making the four-member ring, completely consistent with the experiments.

2b
TS1	TS2
TS3

Figure 2. UBLYP/6-31G(d) optimized structures of 2b, TS1, TS2, and TS3.

References

1) Cinar, M. E.; Vavilala, C.; Fan, J.; Schmittel, M., "The thermal C²-C⁶/[2 + 2] cyclisation of enyne-allenes: Reversible diradical formation," Org. Biomol. Chem. 2011, 9, 3776-3779, DOI: 10.1039/C0OB01275K

InChIs

1b: InChI=1/C21H20/c1-21(2,3)17-9-14-19-12-7-8-13-20(19)16-15-18-10-5-4-6-11-18/h4-8,10-14,17H,1-3H3/t9-/m0/s1
InChIKey=HRQIWBDQUVQGEK-VIFPVBQEBW>

3b: InChI=1/C21H20/c1-21(2,3)20-17-13-15-11-7-8-12-16(15)19(17)18(20)14-9-5-4-6-10-14/h4-13,20H,1-3H3
InChIKey=GKHJKEWSMNKHEN-UHFFFAOYAW

While many pericyclic reactions proceed in a concerted fashion, the stepwise pathway is a distinct possibility. Fernandez, Sierra and Torres report on an interesting [8+2] cycloaddition that
is decidedly stepwise, confirmed through trapping of the intermediate zwitterion.¹

The reaction of 1 with 2 was examined at M06-2x/6-311+G(d) (optimized geometries of the critical points are shown in Figure 1). The first transition state (TS1) has nitrogen acting as a nucleophile, attacking the carbonyl carbon of ketene to give 3. The barrier is 11.6 kcal mol^-1, and 3 lies 0.7 kcal mol^-1 above reactants. While 3 might be described with a tropyllium cation resonance structure, the ring is in fact non-planar and both the NICS(0) and NICS(1)_zz values are positive. The ring is therefore antiaromatic, consistent with the endoergonicity of this step. Closure of the zwitterion through TS2 leads to the formal [8+2] product, with the barrier for this second step slightly lower than the barrier for the first step. Overall, the reaction is quite exothermic.

Scheme 1 (relative energies in kcal mol^-1)

TS1	3
TS2	4

Figure 1. MO6-2x/6-311+G(d) optimized Structures of 3, 4, and the transition states leading to them (TS1 and TS2).

Experiments were performed with a variety of acyl chloride precursors to ketenes (Scheme 2), and along with the [8+2] product, a second product (5) incorporating 2 equivalents of ketene is found; in fact, if the R group is benzyloxy or t-butyl, 5 is the only observed product. This second product comes about via trapping of the intermediate 3. Mixing phenylketene with 4a (where the R group is phenyl) gives no reaction, thus precluding the intermediacy of 4 on the path to 5. MO6-2x computations of the trapping of 3 with phenylketenes indicates a barrier (TS3, see Figure 2) of 9.6 kcal mol^-1, very close to the barrier height of the second TS for ring closure of the [8+2] pathway, supporting the competition between trapping of the intermediate and progress on to the [8+2] product.

Scheme 2.

TS3

Figure 2. MO6-2x/6-311+G(d) optimized Structures of TS3.

References

(1) Lage, M. L.; Fernandez, I.; Sierra, M. A.; Torres, M. R., "Trapping Intermediates in an [8 + 2] Cycloaddition Reaction with the Help of DFT Calculations," Org. Lett., 2011, ASAP, DOI: 10.1021/ol200910z

InChIs

1: InChI=1/C8H6O/c9-7-6-8-4-2-1-3-5-8/h1-6H
InChIKey=RZGZTQYTDRQOEY-UHFFFAOYAC

2: InChI=1/C7H7N/c8-7-5-3-1-2-4-6-7/h1-6,8H
InChIKey=NHNIVEADUHCPRP-UHFFFAOYAI

3: InChI=1/C15H13NO/c17-15(12-13-8-4-3-5-9-13)16-14-10-6-1-2-7-11-14/h1-12,17H/b15-12-/f/h17h,16H
InChIKey=AFLGFPOCUCTUAS-UJUNEOEYDT

4: InChI=1/C15H13NO/c17-15-14(11-7-3-1-4-8-11)12-9-5-2-6-10-13(12)16-15/h1-10,12,14H,(H,16,17)/t12-,14+/m1/s1/f/h16H
InChIKey=BBJCGQGFRRQHHS-KEKMKNANDW