Archive for the 'Houk' Category

Mechanism of dimethyldioxirane oxidation

Dimethyldioxirane can oxidize alkanes to alcohols. The mechanism for the oxidation has been controversial, ranging from concerted, to radical intermediates to an H-abstraction—O-rebound mechanism. Yang, Yu, and Houk now offer a molecular dynamics examination of the reaction of dimethyldioxirane with isobutane.1

Gas–phase (U)B3LYP/6-311++G(d,p)//(U)B3LYP/6-31G(d) computations give critical points outlined in the reaction below. The structures of the transition states and the intermediate are shown in Figure 1.

TS1
26.6
(25.9)

INT
8.6
(9.3)

TS2
8.6
(-0.8)

Figure 1. (U)B3LYP/6-31G(d) optimized geometries of TS1, INT, and TS2. Relative free energies (kcal mol-1) in the gas (top) and solution (bottom) phases

The PES indicates a rebound mechanism, though in acetone solution phase, there was no transition state located for the second step; it appears to be barrierless. It should be noted that the size of the barrier is very small even in the gas phase. The energy given in Figure 1 is for the gas phase structure computed in solution.

Trajectories for both gas and solution phase were computed. For the gas phase, about 90% of the trajectories lead to separated radicals, but in an acetone about 90% of the trajectories lead directly to the alcohol, with only 10% leading to radicals. Even so, the acetone trajectories divide into two types, a dynamically concerted path where the time gap between the formation of the new C-O and O-H bonds is less than 60 fs, and a dynamically stepwise path where the time gap is greater than 60 fs, though for the trajectories that lead to product the gap is typically still less than 150 fs.

References

(1)  Yang, Z.; Yu, P.; Houk, K. N. "Molecular Dynamics of Dimethyldioxirane C–H Oxidation," J. Am. Chem. Soc. 2016, 138, 4237-4242, DOI: 10.1021/jacs.6b01028.

InChIs

Dimethyldioxirane: InChI=1S/C3H6O2/c1-3(2)4-5-3/h1-2H3
InChIKey=FFHWGQQFANVOHV-UHFFFAOYSA-N

Isobutane: InChI=1S/C4H10/c1-4(2)3/h4H,1-3H3
InChIKey=NNPPMTNAJDCUHE-UHFFFAOYSA-N

Houk Steven Bachrach 06 Jun 2016 No Comments

Diels-Alder reactions of some arenes

Houk has examined the Diels-Alder reaction involving ethene with benzene 1 and all of its aza-substituted isomers having four or fewer nitrogen atoms 2-11.1 The reactions were computed at M06-2X/6-311+G(d,p).

All of the possible Diels-Alder reactions were examined, and they can be classified in terms of whether two new C-C bonds are formed, one new C-C and one new C-N bond are formed, or two new C-N bonds are formed. Representative transition states of these three reaction types are shown in Figure 1, using the reaction of 7 with ethene.

Figure 1. M06-2X/6-311+G(d,p) optimized transition states for the Diels-Alders reactions of 7 with ethene.

A number of interesting trends are revealed. For a given type of reaction (as defined above), as more nitrogens are introduced into the ring, the activation energy decreases. Forming two C-C bonds has a lower barrier than forming a C-C and a C-N, which has a lower barrier than forming two C-N bonds. The activation barriers are linearly related to the aromaticity of the ring defined by either NICS(0) or aromatic stabilization energy, with the barrier decreasing with decreasing aromaticity. The barrier is also linearly related to the exothermicity of the reaction.

The activation barrier is also linearly related to the distortion energy. With increasing nitrogen substitution, the ring becomes less aromatic, and therefore more readily distorted from planarity to adopt the transition state structure.

References

(1) Yang, Y.-F.; Liang, Y.; Liu, F.; Houk, K. N. "Diels–Alder Reactivities of Benzene, Pyridine, and Di-, Tri-, and Tetrazines: The Roles of Geometrical Distortions and Orbital Interactions," J. Am. Chem. Soc. 2016, 138, 1660-1667, DOI: 10.1021/jacs.5b12054.

Aromaticity &Diels-Alder &Houk Steven Bachrach 26 Apr 2016 No Comments

Cyclization reaction of 1,2-cyclohexadiene

1,2-Cyclohexadiene 1 is a very strained and highly reactive species. Houk, Garg and co-workers report on its use as the ene component in a cyclization with a 1,3-dipole, namely nitrones.1 For example, 1 reacts with nitrone 2 to give the cycloadducts 3a and 3b in a ratio of 8.9:1.

To investigate the mechanism of this reaction, they optimized the structures of all compounds at CPCM(acetonitrile)B3LYP/6-31G(d) and single-point energies were obtained using the B3LYP-D3 functional. The structures of some pertinent critical points are shown in Figure 1. They did locate a concerted transition state (TS1) leading to 3a, with a barrier of 14.5 kcal mol-1, but could not find a concerted TS leading to 3b. (Also, the barriers leading to the other regioisomer are much higher than the ones leading to the observed products.) Rather, they identified a stepwise transition state (TS2) with a barrier of nearly the same energy (14.4 kcal mol-1) that leads to the intermediate (INT), which lies 16.5 kcal mol-1 below reactants. They located two transition states from his intermediate, TS3a and TS3b, leading to the two different products. The barrier to 3a is 1.2 kcal mol-1 lower than the barrier leading to 3b, and this corresponds nicely with the observed diastereoselectivity.

1
(0.0)

TS1
(14.5)

TS2
(14.4)

 

INT
(-16.5)

 

TS3a
(-7.4)

TS3b
(-6.2)

Figure 1. CPCM(acetonitrile)B3LYP/6-31G(d) optimized geometries and CPCM(acetonitrile)B3LYP-D3/6-31G(d) free energies.

References

(1) Barber, J. S.; Styduhar, E. D.; Pham, H. V.; McMahon, T. C.; Houk, K. N.; Garg, N. K.
"Nitrone Cycloadditions of 1,2-Cyclohexadiene," J. Am. Chem. Soc. 2016, 138, 2512-2515, DOI: 10.1021/jacs.5b13304.

InChIs

1: InChI=1S/C6H8/c1-2-4-6-5-3-1/h1,5H,2,4,6H2
InChIKey=NMGSDTSOSIPXTN-UHFFFAOYSA-N

2: InChI=1S/C11H15NO/c1-11(2,3)12(13)9-10-7-5-4-6-8-10/h4-9H,1-3H3/b12-9-
InChIKey=IYSYLWYGCWTJSG-XFXZXTDPSA-N

3a: InChI=1S/C17H23NO/c1-17(2,3)18-16(13-9-5-4-6-10-13)14-11-7-8-12-15(14)19-18/h4-6,9-11,15-16H,7-8,12H2,1-3H3/t15-,16-/m0/s1
InChIKey=HQIBSHJEOJPFTI-HOTGVXAUSA-N

3b: InChI=1S/C17H23NO/c1-17(2,3)18-16(13-9-5-4-6-10-13)14-11-7-8-12-15(14)19-18/h4-6,9-11,15-16H,7-8,12H2,1-3H3/t15-,16+/m1/s1
InChIkey=HQIBSHJEOJPFTI-CVEARBPZSA-N

cycloadditions &Houk Steven Bachrach 11 Apr 2016 No Comments

Mechanism of organocatalysis by Cinchona alkaloids

Cinchona alkaloids cat catalyze reactions, such as shown in Reaction 1. Wynberg1 proposed a model to explain the reaction, shown in Scheme 1, based on NMR. Grayson and Houk have now used DFT computations to show that the mechanism actually reverses the arrangements of the substrates.2

Reaction 1

Scheme 1.


Wynberg Model


Grayson and Houk Model

M06-2X/def2-TZVPP−IEFPCM(benzene)//M06-2X/6-31G(d)−IEFPCM(benzene) computations show that the precomplex of catalyst 3 with nucleophile 1 and Michael acceptor 2 is consistent with Wynberg’s model. The alternate precomplex is 5.6 kcal mol-1 higher in energy. These precomplexes are shown in Figure 1.

Wynberg precomplex

Grayson/Houk precomplex

Figure 1. Precomplexes structures

However, the lowest energy transition state takes the Grayson/Houk pathway and leads to the major isomer observed in the reaction. The Grayson/Houk TS that leads to the minor product has a barrier that is 3 kcal mol-1 higher in energy. The lowest energy TS following the Wynberg path leads to the minor product, and is 2.2 kcal mol-1 higher than the Grayson/Houk path. These transition states are shown in Figure 2. The upshot is that complex formation is not necessarily indicative of the transition state structure.

Wynberg TS (major)
Rel ΔG = 5.3

Wynberg TS (minor)
Rel ΔG = 2.2

Grayson/Houk TS (major)
Rel ΔG = 0.0

Grayson/Houk TS (minor)
Rel ΔG = 3.0

Figure 2. TS structures and relative free energies (kcal mol-1).

References

(1) Hiemstra, H.; Wynberg, H. "Addition of aromatic thiols to conjugated cycloalkenones, catalyzed by chiral .beta.-hydroxy amines. A mechanistic study of homogeneous catalytic asymmetric synthesis," J. Am. Chem. Soc. 1981, 103, 417-430, DOI: 10.1021/ja00392a029.

(2) Grayson, M. N.; Houk, K. N. "Cinchona Alkaloid-Catalyzed Asymmetric Conjugate Additions: The Bifunctional Brønsted Acid–Hydrogen Bonding Model," J. Am. Chem. Soc. 2016, 138, 1170-1173, DOI: 10.1021/jacs.5b13275.

InChIs

1: InChI=1S/C10H14S/c1-10(2,3)8-4-6-9(11)7-5-8/h4-7,11H,1-3H3
InChIKey=GNXBFFHXJDZGEK-UHFFFAOYSA-N

2: InChI=1S/C8H12O/c1-8(2)5-3-4-7(9)6-8/h3-4H,5-6H2,1-2H3
InChIKey=CDDGRARTNILYAB-UHFFFAOYSA-N

3: InChI=1S/C18H22N2O/c1-12-11-20-9-7-13(12)10-17(20)18(21)15-6-8-19-16-5-3-2-4-14(15)16/h2-6,8,12-13,17-18,21H,7,9-11H2,1H3/t12?,13?,17?,18-/m1/s1
InChIKey=ZOZLJWFJLBUKKL-NKHWWFDVSA-N

4: InChI=1S/C18H26OS/c1-17(2,3)13-6-8-15(9-7-13)20-16-10-14(19)11-18(4,5)12-16/h6-9,16H,10-12H2,1-5H3/t16-/m0/s1
InChIKey=XUTYYZOSKLYWLW-INIZCTEOSA-N

Houk &Michael addition &stereoinduction Steven Bachrach 03 Mar 2016 No Comments

QM/MM trajectory of an aqueous Diels-Alder reaction

I discuss the aqueous Diels-Alder reaction in Chapter 7.1 of my book. A key case is the reaction of methyl vinyl ketone with cyclopentadiene, Reaction 1. The reaction is accelerated by a factor of 740 in water over the rate in isooctane.1 Jorgensen argues that this acceleration is due to stronger hydrogen bonding to the ketone than in the transition state than in the reactants.2-4

Rxn 1

Doubleday and Houk5 report a procedure for calculating trajectories including explicit water as the solvent and apply it to Reaction 1. Their process is as follows:

  1. Compute the endo TS at M06-2X/6-31G(d) with a continuum solvent.
  2. Equilibrate water for 200ps, defined by the TIP3P model, in a periodic box, with the transition state frozen.
  3. Continue the equilibration as in Step 2, and save the coordinates of the water molecules after every addition 5 ps, for a total of typically 25 steps.
  4. For each of these solvent configurations, perform an ONIOM computation, keeping the waters fixed and finding a new optimum TS. Call these solvent-perturbed transition states (SPTS).
  5. Generate about 10 initial conditions using quasiclassical TS mode sampling for each SPTS.
  6. Now for each the initial conditions for each of these SPTSs, run the trajectories in the forward and backward directions, typically about 10 of them, using ONIOM to compute energies and gradients.
  7. A few SPTS are also selected and water molecules that are either directly hydrogen bonded to the ketone, or one neighbor away are also included in the QM portion of the ONIOM, and trajectories computed for these select sets.

The trajectory computations confirm the role of hydrogen bonding in stabilizing the TS preferentially over the reactants. Additionally, the trajectories show an increasing asynchronous reactions as the number of explicit water molecules are included in the QM part of the calculation. Despite an increasing time gap between the formation of the first and second C-C bonds, the overwhelming majority of the trajectories indicate a concerted reaction.

References

(1) Breslow, R.; Guo, T. "Diels-Alder reactions in nonaqueous polar solvents. Kinetic
effects of chaotropic and antichaotropic agents and of β-cyclodextrin," J. Am. Chem. Soc. 1988, 110, 5613-5617, DOI: 10.1021/ja00225a003.

(2) Blake, J. F.; Lim, D.; Jorgensen, W. L. "Enhanced Hydrogen Bonding of Water to Diels-Alder Transition States. Ab Initio Evidence," J. Org. Chem. 1994, 59, 803-805, DOI: 10.1021/jo00083a021.

(3) Chandrasekhar, J.; Shariffskul, S.; Jorgensen, W. L. "QM/MM Simulations for Diels-Alder
Reactions in Water: Contribution of Enhanced Hydrogen Bonding at the Transition State to the Solvent Effect," J. Phys. Chem. B 2002, 106, 8078-8085, DOI: 10.1021/jp020326p.

(4) Acevedo, O.; Jorgensen, W. L. "Understanding Rate Accelerations for Diels−Alder Reactions in Solution Using Enhanced QM/MM Methodology," J. Chem. Theor. Comput. 2007, 3, 1412-1419, DOI: 10.1021/ct700078b.

(5) Yang, Z.; Doubleday, C.; Houk, K. N. "QM/MM Protocol for Direct Molecular Dynamics of Chemical Reactions in Solution: The Water-Accelerated Diels–Alder Reaction," J. Chem. Theor. Comput. 2015, , 5606-5612, DOI: 10.1021/acs.jctc.5b01029.

Diels-Alder &Houk &Solvation Steven Bachrach 02 Feb 2016 1 Comment

Dynamics in the reaction of tetrazine with cyclopropene

Houk and Doubleday report yet another example of dynamic effects in reactions that appear to be simple, ordinary organic reactions.1 Here they look at the Diels-Alder reaction of tetrazine 1 with cyclopropene 2. The reaction proceeds by first crossing the Diels-Alder transition state 3 to form the intermediate 4. This intermediate can then lose the anti or syn N2, through 5a or 5s, to form the product 6. The structures and relative energies, computed at M06-2X/6-31G(d), of these species are shown in Figure 1.

3
17.4

4
-33.2

5a
-28.9

5s
-20.0

6
-86.2

Figure 1. M06-2X/6-31G(d) optimized geometries and energies (relative to 1 + 2) of the critical points along the reaction of tetrazine with cyclopropene.

The large difference in the activation barriers between crossing 5a and 5s (nearly 9 kcal mol-1) suggests, by transition state theory, a preference of more than a million for loss of the anti N2 over the syn N2. However, quasiclassical trajectory studies, using B3LYP/6-31G(d), finds a different situation. The anti pathway is preferred, but only by a 4:1 ratio! This dynamic effect arises from a coupling of the v3 mode which involves a rocking of the cyclopropane ring that brings a proton near the syn N2 functionality, promoting its ejection. In addition, the trajectory studies find short residence times within the intermediate neighborhood for the trajectories that lead to the anti product and longer residence times for the trajectories that lead to the syn product. All together, a very nice example of dynamic effects playing a significant role in a seemingly straightforward organic reaction.

References

(1) Törk, L.; Jiménez-Osés, G.; Doubleday, C.; Liu, F.; Houk, K. N. "Molecular Dynamics of the Diels–Alder Reactions of Tetrazines with Alkenes and N2 Extrusions from Adducts," J. Am. Chem. Soc. 2015, 137, 4749-4758, DOI: 10.1021/jacs.5b00014.

InChIs

1: InChI=1S/C2H2N4/c1-3-5-2-6-4-1/h1-2H
InChIKey=HTJMXYRLEDBSLT-UHFFFAOYSA-N

2: InChI=1S/C3H4/c1-2-3-1/h1-2H,3H2
InChIKey=OOXWYYGXTJLWHA-UHFFFAOYSA-N

4: InChI=1S/C5H6N4/c1-2-3(1)5-8-6-4(2)7-9-5/h2-5H,1H2
InChIKey=JGSMBFYJCNPYDM-UHFFFAOYSA-N

6: InChI=1S/C5H6N2/c1-4-2-6-7-3-5(1)4/h2-5H,1H2
InChIKey=RYJFHKGQZKUXEH-UHFFFAOYSA-N

Diels-Alder &Dynamics &Houk Steven Bachrach 09 Nov 2015 No Comments

Dyotropic rearrangement

Houk and Vanderwal have examined the dyotropic rearrangement of an interesting class of polycyclic compounds using experimental and computational techniques.1 The parent reaction takes the bicyclo[2.2.2]octadiene 1 into the bicyclo[3.2.1]octadiene 3. The M06-2X/6-311+G(d,p)/B3LYP/6-31G(d) (with CPCM simulating xylene) geometries and relative energies are shown in Figure 1. The calculations indicate a stepwise mechanism, with an intervening zwitterion intermediate. The second step is rate determining.

1
(0.0)

TS1
(35.6)

2
(21.9)

TS2
(40.1)




3
(-4.2)

Figure 1. B3LYP/6-31G(d) and relative energies (kcal mol-1) at M06-2X/6-311+G(d,p).

Next they computed the activation barrier for the second TS for a series of substituted analogs of 1, with various electron withdrawing group as R1 and electron donating groups as R2, and compared them with the experimental rates.

Further analysis was done by relating the charge distribution in these TSs with the relative rates, and they find a nice linear relationship between the charge and ln(krel). This led to the prediction that a cyano substituent would significantly activate the reaction, which was then confirmed by experiment. Another prediction of a rate enhancement with Lewis acids was also confirmed by experiment.

A last set of computations addressed the question of whether a ketone or lactone would also undergo this dyotropic rearrangement. The lactam turns out to have the lowest activation barrier by far.

References

(1) Pham, H. V.; Karns, A. S.; Vanderwal, C. D.; Houk, K. N. "Computational and Experimental Investigations of the Formal Dyotropic Rearrangements of Himbert Arene/Allene Cycloadducts," J. Am. Chem. Soc. 2015, 137, 6956-6964, DOI: 10.1021/jacs.5b03718.

InChIs

1: InChI=1S/C11H11NO/c1-12-10(13)7-9-6-8-2-4-11(9,12)5-3-8/h2-5,7-8H,6H2,1H3
InChIKey=MNYYUIQDOAXLTK-UHFFFAOYSA-N

3: InChI=1S/C11H11NO/c1-12-10(13)6-9-3-2-8-4-5-11(9,12)7-8/h2-6,8H,7H2,1H3
InChIKey=OHEBSZKLNGLATD-UHFFFAOYSA-N

Houk Steven Bachrach 29 Jun 2015 1 Comment

Molecular rotor and C-Hπ interaction

Molecular rotors remain a fascinating topic – the idea of creating a miniature motor just seems to capture the imagination of scientists. Garcia-Garibay and his group have synthesized the interesting rotor 1, and in collaboration with the Houk group, they have utilized computations to help understand the dynamics of this rotor.1


1

The x-ray structure of this compound, shown in Figure 1, displays two close interactions of a hydrogen on the central phenyl ring with the face of one of the steroidal phenyl rings. Rotation of the central phenyl ring is expected to then “turn off” one or both of these C-Hπ interactions. The authors argue this as a competition between the molecule sampling an enthalpic region, where the molecule has one or two favorable C-Hπ interactions, and the large entropic region where these C-Hπ interactions do not occur, but this space is expected to have a large quantity of energetically similar conformations.

x-ray

1a

1b

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

Variable temperature NMR finds the central phenyl hydrogen with a chemical shift of 6.55ppm at 295 K but at 6.32 ppm at 222 K. This suggest as freezing of the conformations at low temperature favoring those conformations possessing the internal C-Hπ interactions. M06-2X/6-31G(d) optimization finds two low-energy conformations with a single C-Hπ interaction. These are shown in Figure 1. No competing conformation was found to have two such interactions. Computations of the chemical shifts of these conformations show the upfield shift of the central phenyl hydrogens. Fitting these chemical shifts to the temperature data gives ΔH = -1.74 kcal mol-1, ΔS = -5.12 esu and ΔG = -0.21 kcal mol-1 for the enthalpic region to entropic region transition.

References

(1) Pérez-Estrada, S.; Rodrı́guez-Molina, B.; Xiao, L.; Santillan, R.; Jiménez-Osés, G.; Houk, K. N.; Garcia-Garibay, M. A. "Thermodynamic Evaluation of Aromatic CH/π Interactions and Rotational Entropy in a Molecular Rotor," J. Am. Chem. Soc. 2015, 137, 2175-2178, DOI: 10.1021/ja512053t.

InChIs

1: InChI=1S/C48H54O4/c1-45-23-19-39-37-15-11-35(51-3)29-33(37)9-13-41(39)43(45)21-27-47(45,49)25-17-31-5-7-32(8-6-31)18-26-48(50)28-22-44-42-14-10-34-30-36(52-4)12-16-38(34)40(42)20-24-46(44,48)2/h5-8,11-12,15-16,29-30,39-44,49-50H,9-10,13-14,19-24,27-28H2,1-4H3
InChIKey=CXZHCTLIHKZRMW-UHFFFAOYSA-N

Aromaticity &Houk &Hydrogen bond Steven Bachrach 23 Mar 2015 No Comments

Two review articles for the general audience

In trying to clean up my in-box of articles for potential posts, I write here about two articles for a more general audience, authored by two of the major leaders in computational organic chemistry.

Ken Houk offers an overview of how computational simulation is a partner with experiment and theory in aiding and guiding our understanding of organic chemistry.1 The article is written for the non-specialist, really even more for the non-scientist. Ken describes how computations have helped understand relatively simple reactions like pericyclic reactions, that then get more subtle when torquoselection is considered, to metal-catalysis, to designed protein catalysts. If you are ever faced with discussing just what you do as a computational chemist at a cocktail party, this article is a great resource of how to explain our science to the interested lay audience.

Paul Schleyer adds a tutorial on transition state aromaticity.2 The authors discusses a variety of aromaticity measures (energetics, geometry, magnetic properties) that can be employed to analyze the nature of transition states, in addition to ground state molecules. This article provides a very clear description of the methods and a few examples. It is written for a more specialized audience than Houk’s article, but is nonetheless completely accessible to any chemist, even those with no computational background.

References

(1) Houk, K. N.; Liu, P. "Using Computational Chemistry to Understand & Discover Chemical Reactions," Daedalus 2014, 143, 49-66, DOI: 10.1162/DAED_a_00305.

(2) Schleyer, P. v. R.; Wu, J. I.; Cossio, F. P.; Fernandez, I. "Aromaticity in transition structures," Chem. Soc. Rev. 2014, 43, 4909-4921, DOI: 10.1039/C4CS00012A.

Houk &Schleyer Steven Bachrach 22 Dec 2014 No Comments

Diels-Alder reactions of Fullerene

Diels-Alder reaction involving fullerenes have been known for some time. They occur across the [6,6] double bond of C60, the one between two fused 6-member rings. Houk and Briseno report on the Diels-Alder reaction of C60 with pentacene 1 and bistetracene 2 and compare their computations with experiments.1


Pentacene and bistetracene ring numbering convention

Computations were performed for the reaction of 1 and 2 with C60 at M06-2x/6-31G(d)//M062x-3-21G*. The reaction can occur with the dienophile being either ring 1, 2, or 3 of pentacene and ring 1, 2, 3, or 4 of bistetracene. They located TSs and products for all of these possibilities. Select TSs and products are shown in Figure 1.

For the reaction of 1a, the lowest energy TS is for the reaction at the central ring (ring 3), and the resulting product is the lowest energy product. The transition state (PT_TS3) is shown in Figure 1. This TS has the least distortion energy of the three possibilities, because reacting at this central ring destroys the least amount of aromaticity of pentacene. For the reaction of 1b, the lowest barrier is again for reaction of ring 3 (through TMSPT_TS3). However, the product from the reaction with ring 2 (TMSPT_P2) is lower in free energy than TMSPT­_P3, likely caused by steric interactions with the silyl substituents. This actually matches up with experiments which indicate that an analogue of TMSPT_P2 is the kinetic product but TMSPT_P3 is the thermodynamic product.

PT_TS3

TMSPT_­TS3

TMSPT_P2

TMSPT_P3

BT_TS2

BT_P2

Figure 1. M06-2x/3-21G* optimized geometries.
(Once again a reminder that clicking on any of these structures will launch JMol and you’ll be able to visualize and manipulate this structure in 3-D.)

The computations involving the Diels-Alder reaction of C60 with either 2a or 2b come to the same conclusion. In both cases, the lowest barrier is for the reaction at ring 2, and the product of the reaction at this same ring is the only one that is endoergonic. The geometries of BT_TS2 and BT_P2 are shown in Figure 1. More importantly, the barrier for the Diels-Alder reaction involving 2a and 2b are at least 6 kcal mol-1 higher than the barriers for the reaction of 1a and 1b, in complete agreement with experiments that show little reaction involving analogues of 2b with C60, while analogues of 1b are reasonably rapid.

References

(1) Cao, Y.; Liang, Y.; Zhang, L.; Osuna, S.; Hoyt, A.-L. M.; Briseno, A. L.; Houk, K. N. "Why Bistetracenes Are Much Less Reactive Than Pentacenes in Diels–Alder Reactions with Fullerenes," J. Am. Chem. Soc. 2014, 136, 10743-10751, DOI: 10.1021/ja505240e.

Diels-Alder &fullerene &Houk Steven Bachrach 29 Sep 2014 No Comments

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