Archive for October, 2012

DSD-DFT – a double hybrid variation

I just returned from the Southwest Theoretical Chemistry Conference held at Texas A&M University. My thanks again to Steven Wheeler for the invitation to speak at the meeting and for putting together a very fine program and conference.

Among the many interesting talks was one by Sebastian Kozuch who reported on an interesting double hybrid methodology.1,2 Working with Jan Martin, they defined a procedure that Kozuch referred to as “putting Stefan Grimme into a blender”. They extend the double hybrid concept first suggested by Grimme that adds on an MP2-like correction functional. Kozuch and Martin substitute a spin-component scaled MP2 (SCS-MP2) model for the original MP2 correction. SCS-MP2 was also proposed by Grimme. Lastly, they add on a dispersion correction, an idea championed by Grimme too. The exchange-correlation term is defined as

EXC = cXEX DFT + (1 – cx)ExHF + cCECDFT + cOEOMP2 + cSESMP2 + s6ED

where cX is the coefficient for the amount of DFT exchange, cC the amount of DFT correlation, cC and cS the amount of opposite- and same-spin MP2, and s6 the amount of dispersion. They name this procedure DSD-DFT for Dispersion corrected, Spin-component scaled Double hybrid DFT.

In their second paper on this subject, they propose the use of the PBEP86 functional for the DFT components.2 Benchmarking against a variety of standard databases, including kinetic data, thermodynamic data, along with inorganic and weakly interacting systems, this method delivers the lowest mean error among a small set of functionals. Kozuch reported at the conference on a number of other combinations and should have a publication soon suggesting an even better method. Importantly, these DSD-DFT computations can be run with most major quantum codes including Orca, Molpro, Q-Chem and Gaussian (with a series of IOP specifications).

While double hybrid methods don’t have quite the performance capabilities of regular DFT, density fitting procedures offer the possibility of a significant reduction in computational time. These DSD-DFT methods are certainly worthy of fuller explorations.


(1) Kozuch, S.; Gruzman, D.; Martin, J. M. L. "DSD-BLYP: A General Purpose Double Hybrid Density Functional Including Spin Component Scaling and Dispersion Correction," J. Phys. Chem. C, 2010, 114, 20801-20808,
DOI: 10.1021/jp1070852

(2) Kozuch, S.; Martin, J. M. L. "DSD-PBEP86: in search of the best double-hybrid DFT with spin-component scaled MP2 and dispersion corrections," Phys. Chem. Chem. Phys. 2011, 13, 20104-20107, DOI: 10.1039/C1CP22592H

DFT Steven Bachrach 30 Oct 2012 1 Comment

Flattening an aromatic bowl

Corranulene 1 is a bowl-shaped aromatic compound. It inverts through a planar transition state with a barrier of at 11.5 kcal mol-1. What changes would be found if one per-phenylated corranulene, making 2?


2a: R=H
2b: R=t-But
2c: R=Cl

Scott1 has prepared 2a-c by arylating corranulene using phenylboroxin and palladium acetate and repeating this arylation four times. Amazing to me is that the yield of 2c is 54%! The BMK/cc-pVDZ optimized structure of 2a is shown in Figure 1. One can readily see that the bowl is nearly flat (click on the image to activate Jmol; the x-ray structure of 2b has the bowl depth of only 0.248 Å, compared to a depth of 0.87 Å in 1.

Interestingly, 2 inverts through a chiral TS (shown in Figure 1) so that inversion does not create the enantiomer! The computed barrier height is only 2.5 kcal mol-1.



Figure 1. BMK/cc-pVDZ optimized structures of 2a and the bowl inversion transition state 2aTS.

The flatter bowl results in longer bonds and wider angles about the rim of 2 than in 1. As one might expect, 2a is very strained: the BMK/cc-pVDZ estimation is that 2 is 53 kcal mol-1 more strained than 1, using the homodesmotic Reaction 1. In total, this is a real nice study of using strain to alter shape.

Reaction 1


(1) Zhang, Q.; Kawasumi, K.; Segawa, Y.; Itami, K.; Scott, L. T. "Palladium-Catalyzed C–H Activation Taken to the Limit. Flattening an Aromatic Bowl by Total Arylation," J. Am. Chem. Soc., 2012, 134, 15664-15667, DOI: 10.1021/ja306992k


1: InChI=1S/C20H10/c1-2-12-5-6-14-9-10-15-8-7-13-4-3-11(1)16-17(12)19(14)20(15)18(13)16/h1-10H

2a: InChI=1S/C80H50/c1-11-31-51(32-12-1)61-62(52-33-13-2-14-34-52)72-65(55-39-19-5-20-40-55)66(56-41-21-6-22-42-56)74-69(59-47-27-9-28-48-59)70(60-49-29-10-30-50-60)75-68(58-45-25-8-26-46-58)67(57-43-23-7-24-44-57)73-64(54-37-17-4-18-38-54)63(53-35-15-3-16-36-53)71(61)76-77(72)79(74)80(75)78(73)76/h1-50H

2b: InChI=1S/C120H130/c1-111(2,3)81-51-31-71(32-52-81)91-92(72-33-53-82(54-34-72)112(4,5)6)102-95(75-39-59-85(60-40-75)115(13,14)15)96(76-41-61-86(62-42-76)116(16,17)18)104-99(79-47-67-89(68-48-79)119(25,26)27)100(80-49-69-90(70-50-80)120(28,29)30)105-98(78-45-65-88(66-46-78)118(22,23)24)97(77-43-63-87(64-44-77)117(19,20)21)103-94(74-37-57-84(58-38-74)114(10,11)12)93(73-35-55-83(56-36-73)113(7,8)9)101(91)106-107(102)109(104)110(105)108(103)106/h31-70H,1-30H3

2c: InChI=1S/C80H40Cl10/c81-51-21-1-41(2-22-51)61-62(42-3-23-52(82)24-4-42)72-65(45-9-29-55(85)30-10-45)66(46-11-31-56(86)32-12-46)74-69(49-17-37-59(89)38-18-49)70(50-19-39-60(90)40-20-50)75-68(48-15-35-58(88)36-16-48)67(47-13-33-57(87)34-14-47)73-64(44-7-27-54(84)28-8-44)63(43-5-25-53(83)26-6-43)71(61)76-77(72)79(74)80(75)78(73)76/h1-40H

Aromaticity Steven Bachrach 22 Oct 2012 3 Comments

Proximity-induced Diels-Alder Reaction

The intramolecular Diels-Alder reaction of 1 occurs slowly, but quantitatively, at room temperature.1 This is unusual as most Diels-Alder cyclizations require heating to typically 200 °C. For example, the related cyclization of 2 requires heating to 170 °C.2 What is the cause for this proximity-induced reaction?

Reaction 1

Reaction 2

Reaction 3

Houk and Baran address this question using a computational approach.3 The Diels-Alder reaction of 2 and a simplified analogue of 1, namely 3, were computed at CPCM/M06-2x/6-311+G(d,p)//B3LYP/6-31G(d). The optimized transition states for the reaction of 2 and 3 are shown in Figure 1. The free energy of activation of 3 is 5.4 kcal mol-1 lower in energy than the free energy of activation of 2. This is consistent with the much faster reaction of 1 than 2 observed in the experiment.



Figure 1. B3LYP/6-31G(d) for the transition states of Reactions 2 and 3.

Partitioning 3 into fragments allows Houk and Baran to apply the distortion model. They find that the rigid diene in 3 (and thereby 1) accelerates the reaction relative to the more flexible diene of 2. Further, strain relief in going from 3 (and thereby 1) to TS3 (and thereby to TS of reaction 1) and the formation of an intramolecular hydrogen bond leads to the lower activation energy of 3, and therefore of 1.


(1) Maimone, T. J.; Voica, A.-F.; Baran, P. S. "A Concise Approach to Vinigrol," Angew. Chem. Int. Ed. 2008, 47, 3054-3056, DOI: 10.1002/anie.200800167.

(2) Diedrich, M. K.; Klärner, F.-G.; Beno, B. R.; Houk, K. N.; Senderowitz, H.; Still, W. C. "Experimental Determination of the Activation Parameters and Stereoselectivities of the Intramolecular Diels−Alder Reactions of 1,3,8-Nonatriene, 1,3,9-Decatriene, and 1,3,10-Undecatriene and Transition State Modeling with the Monte Carlo-Jumping Between Wells/Molecular Dynamics Method," J. Am. Chem. Soc. 1997, 119, 10255-10259, DOI: 10.1021/ja9643331.

(3) Krenske, E. H.; Perry, E. W.; Jerome, S. V.; Maimone, T. J.; Baran, P. S.; Houk, K. N. "Why a Proximity-Induced Diels–Alder Reaction Is So Fast," Org. Lett. 2012, 14, 3016-3019, DOI: 10.1021/ol301083q.


1: InChI=1S/C23H40O2Si/c1-10-12-19(24)21-20(16(3)4)18-13-14-23(21,15-17(18)11-2)25-26(8,9)22(5,6)7/h10-11,15-16,18-21,24H,1-2,12-14H2,3-9H3/t18?,19-,20?,21?,23+/m0/s1

2: InChI=1S/C10H16/c1-3-5-7-9-10-8-6-4-2/h3-5,7H,1-2,6,8-10H2/b7-5+

3: InChI=1S/C20H34O2Si/c1-8-10-18(21)20(15(3)4)14-17-11-12-19(20,13-16(17)9-2)22-23(5,6)7/h8-9,13,15,17-18,21H,1-2,10-12,14H2,3-7H3/t17?,18-,19+,20?/m0/s1

Diels-Alder &Houk Steven Bachrach 08 Oct 2012 2 Comments