Archive for the 'electrocyclization' Category

Fused aromatic ring effect on electrocyclization reactions

Aromaticity and orbital symmetry rules, though seemingly of ancient origin, remain areas of active interest. This paper by Fukazawa, et al combine both issues.1 The multiple-step electrocyclization of 1 gives 2 in a reaction that takes 9 days at 80 °C. What would be the effect of diminishing the aromatic character of the fused rings of 1? Would the reaction be faster or slower?

Before discussing the experimental results, let’s examine the B3LYP/6-31G(d) results for the reaction of 1’, 3 and 5. (Note that a slightly smaller pendant substituent is used in the computations than in the experiment.) The optimized geometries of the critical points along the reaction pathway for the cyclization of 3 are shown in Figure 1.

3
(0.0)

3-TS1
(17.9)

3-INT
(10.4)

3-TS2
(13.3)

4
(-60.7)

Figure 1. B3LYP/6-31G(d) optimized geometries and relative energies (kcal mol-1) for the critical points along the reaction 34.
Remember that all structures on my blog can be viewed interactively by clicking on the image of the molecule.

For 1’, the first barrier (for the 8π cyclization) has a barrier of about 23 kcal mol-1, but the second step (the 4π cyclization) has an even larger barrier of 28 kcal mol-1. However, reducing the aromaticity of one of the fused rings (compound 3) leads to lower barriers of 18 and 13 kcal mol-1. For the cyclization of 5, only a single transition state was found – no intermediate and no second TS – with a barrier of 12 kcal mol-1. Thus, removing these external aromatic rings reduces the barrier of the reaction, and that is exactly what is found experimentally!

References

(1) Fukazawa, A.; Oshima, H.; Shimizu, S.; Kobayashi, N.; Yamaguchi, S. "Dearomatization-Induced Transannular Cyclization: Synthesis of Electron-Accepting Thiophene-S,S-Dioxide-Fused Biphenylene," J. Am. Chem. Soc. 2014, 136, 8738-8745, DOI: 10.1021/ja503499n.

InChIs:

1: InChI=1S/C44H64S4Si4/c1-41(2,3)49(13,14)37-25-29-30-26-38(50(15,16)42(4,5)6)46-34(30)23-24-36-32(28-40(48-36)52(19,20)44(10,11)12)31-27-39(51(17,18)43(7,8)9)47-35(31)22-21-33(29)45-37/h25-28H,1-20H3/b30-29-,32-31-
InChIKey=OCNQBMWQONUVNH-IOYDOZLVSA-N

1’:InChI=1S/C32H40S4Si4/c1-37(2,3)29-17-21-22-18-30(38(4,5)6)34-26(22)15-16-28-24(20-32(36-28)40(10,11)12)23-19-31(39(7,8)9)35-27(23)14-13-25(21)33-29/h17-20H,1-12H3/b22-21-,24-23-
InChIKey=GTFPBRMBCLREPG-ICHHBZPXSA-N

2: InChI=1S/C44H64S4Si4/c1-41(2,3)49(13,14)29-21-25-26-22-30(50(15,16)42(4,5)6)46-38(26)34-33(37(25)45-29)35-36(34)40-28(24-32(48-40)52(19,20)44(10,11)12)27-23-31(47-39(27)35)51(17,18)43(7,8)9/h21-24H,1-20H3
InChIKey=OTDXAOVIIQYYNV-UHFFFAOYSA-N

2’: InChI=1S/C32H40S4Si4/c1-37(2,3)21-13-17-18-14-22(38(4,5)6)34-30(18)26-25(29(17)33-21)27-28(26)32-20(16-24(36-32)40(10,11)12)19-15-23(35-31(19)27)39(7,8)9/h13-16H,1-12H3
InChIKey=IYZNCPPDTHWWCO-UHFFFAOYSA-N

3: InChI=1S/C32H40O2S4Si4/c1-39(2,3)29-17-21-22-18-30(40(4,5)6)37-27(22)15-16-28-24(20-32(38(28,33)34)42(10,11)12)23-19-31(41(7,8)9)36-26(23)14-13-25(21)35-29/h17-20H,1-12H3/b22-21-,24-23-
InChIKey=ZJBDGDJVLGNVOD-ICHHBZPXSA-N

4: InChI=1S/C32H40O2S4Si4/c1-39(2,3)21-13-17-18-14-22(40(4,5)6)36-30(18)26-25(29(17)35-21)27-28(26)32-20(16-24(38(32,33)34)42(10,11)12)19-15-23(37-31(19)27)41(7,8)9/h13-16H,1-12H3
InChIKey=QUSJUOMZBJUGON-UHFFFAOYSA-N

5: InChI=1S/C32H40O8S4Si4/c1-45(2,3)29-17-21-22-18-30(46(4,5)6)42(35,36)26(22)15-16-28-24(20-32(44(28,39)40)48(10,11)12)23-19-31(47(7,8)9)43(37,38)27(23)14-13-25(21)41(29,33)34/h17-20H,1-12H3/b22-21-,24-23-
InChIKey=NNZTUSIYEPMHMP-ICHHBZPXSA-N

6: InChI=1S/C32H40O8S4Si4/c1-45(2,3)21-13-17-18-14-22(46(4,5)6)42(35,36)30(18)26-25(29(17)41(21,33)34)27-28(26)32-20(16-24(44(32,39)40)48(10,11)12)19-15-23(47(7,8)9)43(37,38)31(19)27/h13-16H,1-12H3
InChIKey=JZHQQYXUIQXWLQ-UHFFFAOYSA-N

Aromaticity &electrocyclization Steven Bachrach 22 Jul 2014 1 Comment

Benzene Dimers – [2+2] and [4+2]

Hoffmann1 reports on a number of new benzene dimer structures, notably 5-8, whose RIJCOSX-MP2/cc-pVTZ2 structures are shown in Figure 1. A few of these new dimers are only somewhat higher in energy than the known dimers 1-4. The energies of these dimers, relative to two isolated benzene molecules, are listed in Table 1.

1

2

3

4

5

6

7

8

Figure 1. RIJCOSX-MP2/cc-pVTZ optimized geometries of 1-8.

Table 1. Energy (kcal mol-1) of the dimers relative to two benzene molecules and activation energy for reversion to two benzene molecules.


Compound

Erel

Eact

1

50.9

29

2

49.9

 

3

38.2

9

4

58.7

19

5

71.9

30

6

49.9

36

7

60.8

27

8

98.8

28


The energy for reversion of the isomers 5-8 to two isolated benzene molecules is calculated to be fairly large, and so they should be stable relative to that decomposition mode. They also examined a series of other decomposition modes, including [1,5]-hydrogen migration, all of which had barriers of 21 kcal mol-1 or greater, retrocyclization ([2+2]), for which they could not locate transition states, electrocyclic ring opening (Cope), with barriers of at least 17 kcal mol-1 and dimerization – some of which had relatively small enthalpic barriers of 4-5 kcal mol-1. However, the dimerizations all have very unfavorable entropic activation barriers.

So, the conclusion is that all of the novel dimers (4-8) can be reasonable expected to hang around for some time and therefore are potential synthetic targets.

References

(1) Rogachev, A. Yu.; Wen, X.-D.; Hoffmann, R. "Jailbreaking Benzene Dimers," J.
Am. Chem. Soc.
, 2012, 134, 8062-8065, DOI:10.1021/ja302597r

(2) Kossmann, S.; Neese, F. "Efficient Structure Optimization with Second-Order Many-Body Perturbation Theory: The RIJCOSX-MP2 Method," J. Chem. Theory Comput., 2010, 6, 2325-2338, DOI: 10.1021/ct100199k

InChIs

1: InChI=1S/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H/t9-,10+,11-,12+
InChIKey=WMPWOGVJEXSFLI-UHFFFAOYSA-N

2: InChI=1S/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H/t9-,10+,11+,12-
InChIKey=WMPWOGVJEXSFLI-IWDIQUIJSA-N

3: InChI=1S/C12H12/c1-2-4-12-10-7-5-9(6-8-10)11(12)3-1/h1-12H/t9?,10?,11-,12+
InChIKey=ONVDJSCNMCYFTI-CAODYFQJSA-N

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

5: InChI=1S/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H/t9-,10-,11+,12+/m1/s1
InChIKey=WMPWOGVJEXSFLI-WYUUTHIRSA-N

6: InChI=1S/C12H12/c1-2-4-12-10-7-5-9(6-8-10)11(12)3-1/h1-12H/t9?,10?,11-,12-/m0/s1
InChIKey=ONVDJSCNMCYFTI-QQFIATSDSA-N

7: InChI=1S/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H/t9-,10-,11-,12+/m1/s1
InChIKey=WMPWOGVJEXSFLI-KKOKHZNYSA-N

8: InChI=1S/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H/t9-,10-,11-,12-
InChIKey=WMPWOGVJEXSFLI-NQYKUJLISA-N

Aromaticity &cycloadditions &electrocyclization Steven Bachrach 04 Jun 2012 No Comments

Acene Dimerization

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 1Panti1-2, 1Psyn1-2, and 1Psyn1-4. 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 1Panti1-2, 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 1Panti1-2. 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

1Panti1-2: InChI=1/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H
InChIKey=WMPWOGVJEXSFLI-UHFFFAOYAP

1Psyn1-2: InChI=1/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H
InChIKey=WMPWOGVJEXSFLI-UHFFFAOYAP

1Psyn1-4: 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

Aromaticity &Diels-Alder &electrocyclization Steven Bachrach 11 Oct 2011 1 Comment

[2+2] cycloaddition of tethered allene-ynes

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

electrocyclization Steven Bachrach 29 Aug 2011 1 Comment

cyclopenta[b]benzofuran – stereochemistry and mechanism of formation

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

electrocyclization &NMR Steven Bachrach 23 Aug 2011 3 Comments

Stepwise cyclization of allene-ynes

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.

a: R1=Ph, R2=R3=H
b: R1=Ph, R2=H,
R3=t-Bu
c: R1=Ph, R2=POPh2,
R3=t-Bu

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

diradicals &electrocyclization Steven Bachrach 16 Aug 2011 1 Comment

Mechanochemistry II

Mosey has a nice follow-up study on the origin of Woodward-Hoffman forbidden ring opening of cyclobutene under mechanical stress.1 (See this blog post discussing the earlier work of Martinez.2) Pulling on cis substituents of a cyclobutene causes the ring to open in a disrotatory fashion. Normally, the WH forbidden pathway is accessed by photolysis which creates a new electronic state. Mosey asks if this same mechanism is occurring during mechanical stress.

On the face of things, this seems unlikely; how can a mechanical force lead to a new electronic state? CASSCF computations with either no applied external force or with varying sized external forces and IRC computations help answer this question. Without an external force, a diradical (or at least a species with high diradical character – and this could be the transition state) is found along the disrotatory pathway. This same diradical is found regardless of the size of the externally applied mechanical force. What does change is the position of the TS along the pathway: as the force increases, the TS becomes earlier, and the reaction barrier diminishes. No change in the electronic state is affected by the applied mechanical stress.

References

(1) Kochhar, G. S.; Bailey, A.; Mosey, N. J., "Competition between Orbitals and Stress in Mechanochemistry," Angew. Chem. Int. Ed., 2010, 49, 7452-7455, DOI: 10.1002/anie.201003978

(2) 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

electrocyclization Steven Bachrach 20 Dec 2010 1 Comment

Torquoselectivity of cyclobutene ring opening

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

Reaction 1

Reaction 2

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?

Reaction 3

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.


Reaction 4
(relative energies in kcal/mol, activation energies above arrows)

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

electrocyclization &Houk Steven Bachrach 23 Jun 2009 No Comments

Mechanochemistry

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

electrocyclization Steven Bachrach 08 Jun 2009 1 Comment

Lewis acid catalysis of 6e- electrocyclizations

While catalysis of many pericyclic reactions have been reported, until now there have been no reports of a catalyzed electrocylization. Bergman, Trauner and coworkers have now identified the use of an aluminum Lewis Acid to catalyze a 6e- electrocyclization.1

They start off by noting that electron withdrawing groups on the C2 position of a triene lowers the barrier of the electrocylization. So they model the carbomethoxy substituted hexatriene (1a-d) with a proton attached to the carbonyl oxygen as the Lewis acid at B3LYP/6-31G**. Table 1 presents the barrier for the four possible isomeric reactions. Only in the case where the substituent is in the 2 position is there a significant reduction in the activation barrier: 10 kcal mol-1.

Table 1. B3LYP/6-31G** activation barriers (kcal mol-1) for the catalyzed (H+) and uncatalyzed electrocylication reaction of carbomethoxy-substituted hexatrienes.

Reactant

Product

Ea

Ea (protonated)


1a


2a

31

35


1b


2a

34

33


1c


2c

24

14


1d


2d

26

24

With these calculations as a guide, they synthesized compounds 3 and 5 and used Me2AlCl as the catalysts. In both cases, significant rate enhancement was observed. The thermodynamic parameters for these electrocylizations are given in Table 2. The aluminum catalyst acts primarily to lower the enthalpic barrier, as predicted by the DFT computations. The effect is not as dramatic as for the computations due likely to a much greater charge dispersal in over the aluminum catalyst (as opposed to the tiny proton in the computations) and the omission of solvent from the calculations.

Table 2. Experimental thermodynamic parameters for the electrocylcization of 3 and 5.


 

Thermal

Catalyzed


ΔH (kcal mol-1)

22.4

20.0

ΔS (e.u.)

-9.2

-11.8

ΔG (kcal mol-1)

25.2

23.5


 

Thermal

Catalyzed


ΔH (kcal mol-1)

20.3

18.1

ΔS (e.u.)

-12.4

-11.6

ΔG (kcal mol-1)

24.0

21.6


References

(1) Bishop, L. M.; Barbarow, J. E.; Bergman, R. G.; Trauner, D., "Catalysis of 6π Electrocyclizations," Angew. Chem. Int. Ed. 2008, 47, 8100-8103, DOI: 10.1002/anie.200803336

InChIs

1a: InChI=1/C8H10O2/c1-3-4-5-6-7-8(9)10-2/h3-7H,1H2,2H3/b5-4-,7-6+
InChIKey=INMLJEKOJCNLTL-SCFJQAPRBY

1b: InChI=1/C8H10O2/c1-3-4-5-6-7-8(9)10-2/h3-7H,1H2,2H3/b5-4-,7-6-
InChIKey=INMLJEKOJCNLTL-RZSVFLSABV

1c: InChI=1/C8H10O2/c1-4-5-6-7(2)8(9)10-3/h4-6H,1-2H2,3H3/b6-5-
InChIKey=QALYADPPGKOFPQ-WAYWQWQTBX

1d: InChI=1/C8H10O2/c1-4-6-7(5-2)8(9)10-3/h4-6H,1-2H2,3H3/b7-6+
InChIKey=BRDQFYBEWWPLFX-VOTSOKGWBR

2a: InChI=1/C8H10O2/c1-10-8(9)7-5-3-2-4-6-7/h2-5>,7H,6H2,1H3
InChIKey=LUFUPKXCMNRVLT-UHFFFAOYAU

2c: InChI=1/C8H10O2/c1-10-8(9)7-5-3-2-4-6-7/h2-3,5H,4,6H2,1H3
InChIKey=KPYYGHDMWKXJCE-UHFFFAOYAC

2d: InChI=1/C8H10O2/c1-10-8(9)7-5-3-2-4-6-7/h3,5-6H,2,4H2,1H3
InChIKey=YCTXQIVXFOMZCV-UHFFFAOYAU

3: InChI=1/C17H20O2/c1-5-16(17(18)19-4)14(3)11-13(2)12-15-9-7-6-8-10-15/h5-12H,1-4H3/b13-12+,14-11-,16-5-
InChIKey=DPBZDJWWRAWHQX-USTKDYFJBV

4: InChI=1/C17H20O2/c1-11-10-12(2)16(17(18)19-4)13(3)15(11)14-8-6-5-7-9-14/h5-10,13,15H,1-4H3/t13-,15-/m1/s1
InChIKey=JFBDOBRQORXZEY-UKRRQHHQBP

5: InChI=1/C16H16O/c1-13(12-14-6-3-2-4-7-14)10-11-15-8-5-9-16(15)17/h2-4,6-8,10-12H,5,9H2,1H3/b11-10-,13-12+
InChIKey=OAQIPONHGIZOBU-JPYSRSMKBG

6: InChI=1/C16H16O/c1-11-7-8-13-14(9-10-15(13)17)16(11)12-5-3-2-4-6-12/h2-8,14,16H,9-10H2,1H3/t14-,16-/m0/s1
InChIKey=MJUGKTLVECDOOO-HOCLYGCPBO

DFT &electrocyclization Steven Bachrach 03 Nov 2008 No Comments