Mechanism of organocatalysis by Cinchona alkaloids

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

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

Calculating large fullerenes

fullerene Steven Bachrach 22 Feb 2016 4 Comments

What is the size of a molecule that will stretch computational resources today? Chan and co-workers have examined some very large fullerenes1 to both answer that question, and also to explore how large a fullerene must be to approach graphene-like properties.

They are interested in predicting the heat of formation of large fullerenes. So, they benchmark the heats of formation of C60 using four different isodesmic reactions (Reaction 1-4), comparing the energies obtained using a variety of different methods and basis sets to those obtained at W1h. The methods include traditional functionals like B3LYP, B3PW91, CAM-B3LYP, PBE1PBE, TPSSh, B98, ωB97X, M06-2X3, and MN12-SX, and supplement them with the D3 dispersion correction. Additionally a number of doubly hybrid methods are tested (again with and without dispersion corrections), such as B2-PLYP, B2GPPLYP, B2K-PLYP, PWP-B95, DSD-PBEPBE, and DSD-B-P86. The cc-pVTZ and cc-pVQZ basis sets were used. Geometries were optimized at B3LYP/6-31G(2df,p).

C60 + 10 benzene → 6 corannulene

Reaction 1

C60 + 10 naphthalene → 8 corannulene

Reaction 2

C60 + 10 phenanthrene → 10 corannulene

Reaction 3

C60 + 10 triphenylene → 12 corannulene

Reaction 4

Excellent results were obtained with DSD-PBEPBE-D3/cc-pVQZ (an error of only 1.8 kJ/mol), though even a method like BMK-D3/cc-pVTZ had an error of only 9.2 kJ/mol. They next set out to examine large fullerenes, including such behemoths as C180, C240, and C320, whose geometries are shown in Figure 1. Heats of formation were obtained using isodesmic reactions that compare back to smaller fullerenes, such as in Reaction 5-8.

C70 + 5 styrene → C60 + 5 naphthalene

Reaction 5

C180 → 3 C60

Reaction 6

C320 + 2/3 C60 → 2 C180

Reaction 7

C180

C240

C320

Figure 1. B3LYP/6-31G(2df,p) optimized geometries of C180, C240, and C320. (Don’t forget that clicking on these images will launch Jmol and allow you to manipulate the molecules in real-time.)

Next, taking the heat of formation per C for these fullerenes, using a power law relationship, they were able to extrapolate out the heat of formation per C for truly huge fullerenes, and find the truly massive fullerenes, like C9680, still have heats of formation per carbon 1 kJ/mol greater than for graphene itself.

References

(1) Chan, B.; Kawashima, Y.; Katouda, M.; Nakajima, T.; Hirao, K. "From C60 to Infinity: Large-Scale Quantum Chemistry Calculations of the Heats of Formation of Higher Fullerenes," J. Am. Chem. Soc. 2016, 138, 1420-1429, DOI: 10.1021/jacs.5b12518.

Atropisomerization within a cyclic compound

Stereochemistry Steven Bachrach 10 Feb 2016 1 Comment

Atropisomers are stereoisomer that differ by axial symmetry, such as in substituted biphenyls or allenes. These acyclic systems have received a fair amount of attention, but now Buevich has looked at atropisomerization that occurs in a ring system.1 1 has a biphenyl as part of the eight-member ring, and the biphenyl can exist in either an M or P orientation. Since C3 is chiral (S), the two isomers are (M,S)-1 and (P,S)-1. Variable temperature NMR analysis concludes that (P,S)-1 is 1.19 kcal mol-1 more stable than (M,S)-1, and the barrier for the interchange (P,S)-1 → (M,S)-1 is 26.77 kcal mol-1.

To identify the process for this atropisomerization process, he utilized B3LYP/6-31G(d) computations of the model system 2. A variety of different techniques were used to identify the local energy minimum conformations of both (M,S)-2 and (P,S)-2, and the lowest energy conformers (M1 for (P,S)-2 and M4 for (M,S)-2) are shown in Figure 1. He then produced a series of 2-D potential energy surfaces varying two of the dihedral angles defining the eight-member ring to help identify potential initial geometries for searching for transition states. (As an aside, this procedure ended up identifying a few additional local energy minima not identified in the initial conformational search – and these all have trans amide groups instead of the cis relationship found initially. These trans isomer are considerably higher in energy than the conformers.) With this model and this computational level, (P,S)-2 is 0.76 kcal mol-1 lower in energy than (M,S)-2.

M1
0.0




TS1
3.54




M2
2.21




TS4
25.83




M4
0.76

 

Table 1. B3LYP/6-31G(d) optimized geometries and relative free energies of some critical points along the lowest energy pathway taking (P,S)-2 → (M,S)-2.

A number of transition states were identified, and the lowest energy pathway that takes M1 into M4 first crosses TS1 to make the minimum M2, which than passes a high barrier (25.8 kcal mol-1) to go to M4. This barrier is in reasonable agreement with the experimental barrier for 1. These TSs are also shown in Figure 1.

Buevich analyzes the conformational process by examination of the changes in the ring dihedral angles following this reaction path. As expected, crossing the highest barrier requires a combination of torsional rotations, but essentially one at a time moving clockwise about the ring.

References

(1) Buevich, A. V. "Atropisomerization of 8-Membered Dibenzolactam: Experimental NMR and Theoretical DFT Study," J. Org. Chem. 2016, 81, 485–501 DOI: 10.1021/acs.joc.5b02321.

InChIs

1: InChI=1S/C27H26N2O/c1-3-12-26-27(30)29(20-21-13-6-5-7-14-21)25-18-11-9-16-23(25)22-15-8-10-17-24(22)28(26)19-4-2/h3-11,13-18,26H,1-2,12,19-20H2/t26-/m0/s1
InChIKey=IYYACMIVKDJSJD-SANMLTNESA-N

2: InChI=1S/C17H18N2O/c1-12-17(20)19(3)16-11-7-5-9-14(16)13-8-4-6-10-15(13)18(12)2/h4-12H,1-3H3/t12-/m0/s1
InChIKey=NIBPKKMKNFOPRM-LBPRGKRZSA-N

QM/MM trajectory of an aqueous Diels-Alder reaction

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

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.

Really short non-bonded HH distances

Uncategorized Steven Bachrach 26 Jan 2016 6 Comments

Setting the record for the shortest non-bonded HH contact has become an active contest. Following on the report of a contact distance of only 1.47 Å that I blogged about here, Firouzi and Shahbazian propose a series of related cage molecules with C-H bonds pointed into their interior.1 The compounds were optimized with a variety of computational methods, and many of them have HH distances well below that of the previous record. The shortest distance is found in 1, shown in Figure 1. The HH distance in 1 is predicted to be less than 1.2 Å with a variety of density functionals and moderate basis sets.

1

Figure 1. Optimized geometry of 1 at ωB97X-D/cc-pVDZ.

References

(1) Firouzi, R.; Shahbazian, S. "Seeking Extremes in Molecular Design: To What Extent May Two “Non-Bonded” Hydrogen Atoms be Squeezed in a Hydrocarbon?," ChemPhysChem 2016, 17, 51-54, DOI: 10.1002/cphc.201501002.

InChIs

1: InChI=1S/C41H44/c1-7-13-25-17-9-3-40-5-11-19(35(17)40)27-15-8-2-39(1,33(13)15)34-14(7)26-18-10-4-41-6-12-20(36(18)41)28(16(8)34)32(27)30-23(11)37(40)21(9)29(31(25)26)22(10)38(41)24(12)30/h7-38H,1-6H2
InChIKey=DMWSEJFKSWCSLI-UHFFFAOYSA-N

Fractional occupancy density

Grimme Steven Bachrach 20 Jan 2016 2 Comments

Assessing when a molecular system might be subject to sizable static (non-dynamic) electron correlation, necessitating a multi-reference quantum mechanical treatment, is perhaps more art than science. In general one suspects that static correlation will be important when the frontier MO energy gap is small, but is there a way to get more guidance?

Grimme reports the use of fractional occupancy density (FOD) as a visualization tool to identify regions within molecules that demonstrate significant static electron correlation.1 The method is based on the use of finite temperature DFT.2,3

The resulting plots of the FOD for a series of test cases follow our notions of static correlation. Molecules, such as alkanes, simple aromatics, and concerted transition states show essentially no fractional orbital density. On the other hand, the FOD plot for ozone shows significant density spread over the entire molecule; the transition state for the cleavage of the terminal C-C bond in octane shows FOD at C1 and C2 but not elsewhere; p-benzyne shows significant FOD at the two radical carbons, while the FOD is much smaller in m-benzyne and is negligible in o-benzyne.

This FOD method looks to be a simple tool for evaluating static correlation and is worth further testing.

References

(1) Grimme, S.; Hansen, A. "A Practicable Real-Space Measure and Visualization of Static Electron-Correlation Effects," Angew. Chem. Int. Ed. 2015, 54, 12308-12313, DOI: 10.1002/anie.201501887.

(2) Mermin, N. D. "Thermal Properties of the Inhomogeneous Electron Gas," Phys. Rev. 1965, 137, A1441-A1443, DOI: 10.1103/PhysRev.137.A1441.

(3) Chai, J.-D. "Density functional theory with fractional orbital occupations," J. Chem. Phys 2012, 136, 154104, DOI: doi: 10.1063/1.3703894.

Dynamic effects in computing NMR (and a patent issue?)

NMR Steven Bachrach 11 Jan 2016 3 Comments

The prediction of NMR chemical shifts and coupling constants through ab initio computation is a major development of the past decade in computational organic chemistry. I have written about many developments on this blog. An oft-used method is a linear scaling of the computed chemical shifts to match those of some test set. Kwan and Liu wondered if the dynamics of molecular motions might be why we need this correction.1

They suggest that the chemical shift can be computed as

<σ> = σ(static molecule using high level computation) + error

where the error is the obtained by using a low level computation taking the difference between the chemical shifts obtained on a dynamic molecule less that obtained with a static molecule. The dynamic system is obtained by performing molecular dynamics of the molecule, following 25 trajectories and sampling every eighth point.

They find outstanding agreement for the proton chemical shift of 12 simple molecules (mean error of 0.02 ppm) and the carbon chemical shift of 19 simple molecules (mean error of 0.5 ppm) without any scaling. Similar excellent agreement is found for a test set of natural products.

They finish up with a discussion of [18]annulene 1. The structure of 1 is controversial. X-ray crystallography indicates a near D6h geometry, but the computed NMR shifts using a D6h geometry are in dramatic disagreement with the experimental values, leading Schleyer to suggest a C2  geometry. Kwan and Liu applied their dynamic NMR method to the D6h, D3h, and C2 structures, and find the best agreement with the experimental chemical shifts are from the dynamic NMR initiated from the D6h geometry. Dynamic effects thus make up for the gross error found with the static geometry, and now bring the experimental and computational data into accord.

One final note on this paper. The authors indicate that they have filed a provisional patent on their method. I am disturbed by this concept of patenting a computational methodology, especially in light of the fact that many other methods have been made available to the world without any legal restriction. For example, full details including scripts to apply Tantillo’s correction method are available through the Cheshire site and a web app to implement Goodman’s DP4 method are available for free. Provisional patents are not available for review from the US Patent Office so I cannot assess just what is being protected here. However, I believe that this action poses a real concern over the free and ready exchange of computational methodologies and ideas.

References

(1) Kwan, E. E.; Liu, R. Y. "Enhancing NMR Prediction for Organic Compounds Using Molecular Dynamics," J. Chem. Theor. Comput. 2015, 11, 5083-5089, DOI: 10.1021/acs.jctc.5b00856.

InChIs

1: InChI=1S/C18H18/c1-2-4-6-8-10-12-14-16-18-17-15-13-11-9-7-5-3-1/h1-18H/b2-1-,3-1+,4-2+,5-3+,6-4+,7-5-,8-6-,9-7+,10-8+,11-9+,12-10+,13-11-,14-12-,15-13+,16-14+,17-15+,18-16+,18-17-
InChIKey=STQWAGYDANTDNA-DWSNDWDZSA-N

Dispersion in organic chemistry – a review and another example

DFT &Schreiner Steven Bachrach 04 Jan 2016 No Comments

The role of dispersion in organic chemistry has been slowly recognized as being quite critical in a variety of systems. I have blogged on this subject many times, discussing new methods for properly treating dispersion within quantum computations along with a variety of molecular systems where dispersion plays a critical role. Schreiner1 has recently published a very nice review of molecular systems where dispersion is a key component towards understanding structure and/or properties.

In a similar vein, Wegner and coworkers have examined the Z to E transition of azobenzene systems (1a-g2a-g) using both experiment and computation.2 They excited the azobenzenes to the Z conformation and then monitored the rate for conversion to the E conformation. In addition they optimized the geometries of the two conformers and the transition state for their interconversion at both B3LYP/6-311G(d,p) and B3LYP-D3/6-311G(d,p). The optimized structure of the t-butyl-substituted system is shown in Figure 1.


a: R=H; b: R=tBu; c: R=Me; d: R=iPr; e: R=Cyclohexyl; f: R=Adamantyl; g: R=Ph

1b

1b-TS-2b

2b

Figure 1. B3LYP-D3/6-311G(d,p) optimized geometries of 1a, 2a, and the TS connecting them.

The experiment finds that the largest activation barriers are for the adamantly 1f and t-butyl 1b azobenzenes, while the lowest barriers are for the parent 1a and methylated 1c azobenzenes.

The trends in these barriers are not reproduced at B3LYP but are reproduced at B3LYP-D3. This suggests that dispersion is playing a role. In the Z conformations, the two phenyl groups are close together, and if appropriately substituted with bulky substituents, contrary to what might be traditionally thought, the steric bulk does not destabilize the Z form but actually serves to increase the dispersion stabilization between these groups. This leads to a higher barrier for conversion from the Z conformer to the E conformer with increasing steric bulk.

References

(1) Wagner, J. P.; Schreiner, P. R. "London Dispersion in Molecular Chemistry—Reconsidering Steric Effects," Angew. Chem. Int. Ed. 2015, 54, 12274-12296, DOI: 10.1002/anie.201503476.

(2) Schweighauser, L.; Strauss, M. A.; Bellotto, S.; Wegner, H. A. "Attraction or Repulsion? London Dispersion Forces Control Azobenzene Switches," Angew. Chem. Int. Ed. 2015, 54, 13436-13439, DOI: 10.1002/anie.201506126.

InChIs

1b: InChI=1S/C28H42N2/c1-25(2,3)19-13-20(26(4,5)6)16-23(15-19)29-30-24-17-21(27(7,8)9)14-22(18-24)28(10,11)12/h13-18H,1-12H3/b30-29-
InChIKey=SOCNVTNVHBWFKC-FLWNBWAVSA-N

2b: InChI=1S/C28H42N2/c1-25(2,3)19-13-20(26(4,5)6)16-23(15-19)29-30-24-17-21(27(7,8)9)14-22(18-24)28(10,11)12/h13-18H,1-12H3/b30-29+
InChIKey=SOCNVTNVHBWFKC-QVIHXGFCSA-N

[5]Radialene

Diels-Alder Steven Bachrach 07 Dec 2015 No Comments

What may be something of a surprise, [5]radialene 1 has only just now been synthesized.1 What makes this especially intriguing is that [3]radialene 2, [4]radialene 3 and [6]radialene 4 have been known for years.

Paddon-Row, Sherburn, and coworkers speculated that [5]radialene must undergo polymerization much more rapidly than the other radialenes. They computed the activation barrier for the Diels-Alder dimerization of the radialenes at G4(MP2). (The optimized structure of 1 and the transition state for the dimerization of 1 are shown in Figure 1.) The activation barrier for the dimerization of 1 is computed to be only 14.3 kJ mol-1, much lower than for the dimerization of 3 (59.2 kJ mol-1) or 4 (31.5 kJ mol-1).

1

TS

Figure 1. G4(MP2) optimized geometries of 1 and the TS for the dimerization of 1.

Application of the distortion/interaction energy model helps to understand why 1 is the outlier among the radialenes. The distortion energy to bring two molecules of 1 to the transition state geometry is about 63 kJ mol-1, and this is much less than for [4]radialene (102 kJ mol-1) or [6]radialene (96 kJ mol-1). The reason lies in that [5]radialene is close to planarity and so only the pyramidalization at one carbon is necessary to reach the TS geometry. For 4, which is in a chair geometry, significant distortion is needed to bring the double bonds into conjugation. For 3, the high distortion energy is due to the significant pyramidalization energy needed.

Another interesting note is that the TSs for the Diels-Alder reactions of the radialenes is bis-pericyclic. The authors point out that dynamic effects may be important – though they did not perform any MD studies.

These computations drove the synthesis of 1 by coordinating it to two equivalents of Fe(CO)3 and then driving off the metals with cerium ammonium nitrate in acetone at -78 °C. The free [5]radialene was then detected by NMR, and it decomposes with a half-life of about 16 min at -20 °C.

References

(1) Mackay, E. G.; Newton, C. G.; Toombs-Ruane, H.; Lindeboom, E. J.; Fallon, T.; Willis, A. C.; Paddon-Row, M. N.; Sherburn, M. S. "[5]Radialene," J. Am. Chem. Soc. 2015, 137, 14653–14659, DOI: 10.1021/jacs.5b07445.

InChIs

1: InChI=1S/C10H10/c1-6-7(2)9(4)10(5)8(6)3/h1-5H2
InChIKey=RVBXYBDJWKWCLW-UHFFFAOYSA-N

Highly efficient Buckycatchers

Aromaticity &fullerene &host-guest Steven Bachrach 30 Nov 2015 No Comments

Capturing buckyballs involves molecular design based on non-covalent interactions. This poses interesting challenges for both the designer and the computational chemist. The curved surface of the buckyball demands a sequestering agent with a complementary curved surface, likely an aromatic curved surface to facilitate π-π stacking interactions. For the computational chemist, weak interactions, like dispersion and π-π stacking demand special attention, particularly density functionals designed to account for these interactions.

Two very intriguing new buckycatchers were recently prepared in the Sygula lab, and also examined by DFT.1 Compounds 1 and 2 make use of the scaffold developed by Klärner.2 In these two buckycatchers, the tongs are corranulenes, providing a curved aromatic surface to match the C60 and C70 surface. They differ in the length of the connector unit.

B97-D/TZVP computations of the complex of 1 and 2 with C60 were carried out. The optimized structures are shown in Figure 1. The binding energies (computed at B97-D/QZVP*//B97-D/TZVP) of these two complexes are really quite large. The binding energy for 1:C60 is 33.6 kcal mol-1, comparable to some previous Buckycatchers, but the binding energy of 2:C60 is 50.0 kcal mol-1, larger than any predicted before.

1

2

Figure 1. B97-D/TZVP optimized geometries of 1:C60and 2:C60.

Measurement of the binding energy using NMR was complicated by a competition for one or two molecules of 2 binding to buckyballs. Nonetheless, the experimental data show 2 binds to C60 and C70 more effectively than any previous host. They were also able to obtain a crystal structure of 2:C60.

References

(1) Abeyratne Kuragama, P. L.; Fronczek, F. R.; Sygula, A. "Bis-corannulene Receptors for Fullerenes Based on Klärner’s Tethers: Reaching the Affinity Limits," Org. Lett. 2015, ASAP, DOI: 10.1021/acs.orglett.5b02666.

(2) Klärner, F.-G.; Schrader, T. "Aromatic Interactions by Molecular Tweezers and Clips in Chemical and Biological Systems," Acc. Chem. Res. 2013, 46, 967-978, DOI: 10.1021/ar300061c.

InChIs

1: InChI=1S/C62H34O2/c1-63-61-57-43-23-45(41-21-37-33-17-13-29-9-5-25-3-7-27-11-15-31(35(37)19-39(41)43)53-49(27)47(25)51(29)55(33)53)59(57)62(64-2)60-46-24-44(58(60)61)40-20-36-32-16-12-28-8-4-26-6-10-30-14-18-34(38(36)22-42(40)46)56-52(30)48(26)50(28)54(32)56/h3-22,43-46H,23-24H2,1-2H3/t43-,44+,45+,46-
InChIKey=RLOJCVYXCBOUQB-RYSLUOGPSA-N

2: InChI=1S/C66H36O2/c1-67-65-51-24-45-43-23-44(42-20-38-34-16-12-30-8-4-27-3-7-29-11-15-33(37(38)19-41(42)43)59-55(29)53(27)56(30)60(34)59)46(45)25-52(51)66(68-2)64-50-26-49(63(64)65)47-21-39-35-17-13-31-9-5-28-6-10-32-14-18-36(40(39)22-48(47)50)62-58(32)54(28)57(31)61(35)62/h3-22,24-25,43-44,49-50H,23,26H2,1-2H3/t43-,44+,49+,50-
InChIKey=JAUUHTKCNSNBMD-NETXOKAWSA-N

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