Archive for December, 2012

t-Butyl radical and anion

Two interesting questions are addressed in a focal-point computational study of t-butyl radical and the t-butyl anion from the Schaefer group.1 First, is the radical planar? EPR and PES studies from the 1970s indicate a pyramidal structure, with an inversion barrier of only 0.64 kcal mol-1. The CCSD(T)/cc-pCVTZ optimized structure of t-butyl radical shows it to be pyramidal with the out-of-plane angle formed by one methyl group and the other three carbons of 22.9°, much less than the 54.7° of a perfect tetrahedron. Focal point analysis give the inversion barrier 0.74 kcal mol-1, in outstanding agreement with experiment.

Second, what is the electron affinity (EA) of the t-butyl radical? Schleyer raised the concern that the alkyl anions may be unbound, and suggested that the electron affinity of t-butyl radical was -9.6 kcal mol-1; in other words, the anion is thermodynamically unstable. This focal-point study shows just how sensitive the EA is to computational method. The HF/CBS value of the EA is -39.59 kcal mol-1 (unbound anion), but the MP2/CBS value is +41.57 kcal mol-1 (bound anion!). The CCSD/aug-cc-pVQZ value is -8.92 while the CCSD(T)/aug-cc-pVQZ value is +4.79 kcal mol-1. The estimated EA at CCSDT(Q)/CBS is -1.88 kcal mol-1, and inclusion of correction terms (including ZPE and relativistic effect) gives a final estimate of the EA as -0.48 kcal mol-1, or a very weakly unbound t-butyl anion. It is somewhat disconcerting that such high-level computations are truly needed for some relatively simple questions about small molecules.


(1) Sokolov, A. Y.; Mittal, S.; Simmonett, A. C.; Schaefer, H. F. "Characterization of the t-Butyl Radical and Its Elusive Anion," J. Chem. Theory Comput. 2012, 8, 4323-4329, DOI: 10.1021/ct300753d.

focal point &Schaefer Steven Bachrach 17 Dec 2012 1 Comment

Basis sets for OR

What is the appropriate basis set to use for computing optical rotations? Hedgård, Jensen, and Kongsted examined the optical rotation of 1-6 using B3LYP and CAM-B3LYP at two different wavelengths.1 They examined a series of different basis sets, including the aug-pCS sets2 (developed for NMR computations), the aug-cc-pVXZ series and 6-311++G(3df,3pd). They compared the computed optical rotation with the different basis sets with the value obtained from an extrapolated basis set computation. The mean absolute deviation using either B3LYP or CAM-B3LYP at the two different basis sets are listed in Table 1. The bottom line is that aug-pcS-2 is the preferred method, but this basis set is rather large and computations of big molecules will be difficult. The aug-pcS-1 set is the best choice for large molecules. Errors with the extensive Pople basis set and the aug-cc-pVXZ sets are quite sizable and of concern (especially at the shorter wavelength). It should also be mentioned that even with the largest aug-pcS basis sets extrapolated to the CBS limit, the computed value of the optical rotation of 3 has the wrong sign! Clearly, basis set choice is not the only issue of concern. We remain in need of a robust methodology for computing optical activity.

Table 1. Mean absolute deviation of the optical activities of 1-6 evaluated at two wavelengths.


589.3 nm

355.0 nm

Basis set































(1) Hedegård, E. D.; Jensen, F.; Kongsted, J. "Basis Set Recommendations for DFT Calculations of Gas-Phase Optical Rotation at Different Wavelengths," J. Chem. Theory Comput. 2012, 8, 4425-4433, DOI: 10.1021/ct300359s

(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

Optical Rotation Steven Bachrach 11 Dec 2012 2 Comments

Aquatolide – structure revision brought on by computed NMR spectra

The natural product aquatolide has the proposed structure 1.1 Before starting to investigate this rather unusual structure – the 2[ladderane] component is rare and likely to be a synthetic challenge – Shaw and Tantillo opted to reassure themselves that the structure is correct.2 They computed the chemical shifts of this structure at mPW1PW91/6-311+G(2d,p)//B3LYP/6-31+G(d,p) including PCM to model chloroform. Surprisingly, the mean absolute deviation of the computed 13C NMR shifts of 1 with the experimental values is 7.23 ppm, with the largest deviation of 24.3 ppm. The largest deviation between 1 and the experimental 1H NMR shifts is 1.31 ppm. These large errors suggested that the structure is wrong. Surveying some 60 different possible alternative structures, largely based on other related compounds found in the same plant, they landed on 2. Here the mean absolute deviation of the computed 13C chemical shifts is only 1.37 ppm, with a maximum deviation of only 4.3 ppm. Similar dramatic improvement is also seen with the proton chemical shifts. Excellent agreement is also seen in the computed 1H-1H coupling constants between those computed for 2 and the experimental spectrum. Crystallization of aquatolide and subsequent determination of the structure using x-ray diffraction confirms that the actual structure of aquatolide is 2.




(1) San Feliciano, A.; Medarde, M.; Miguel del Corral, J. M.; Aramburu, A.; Gordaliza, M.; Barrero, A. F. "Aquatolide. A new type of humulane-related sesquiterpene lactone," Tetrahedron Lett. 1989, 30, 2851-2854, DOI: 10.1016/s0040-4039(00)99142-1

(2) Lodewyk, M. W.; Soldi, C.; Jones, P. B.; Olmstead, M. M.; Rita, J.; Shaw, J. T.; Tantillo, D. J. "The Correct Structure of Aquatolide—Experimental Validation of a Theoretically-Predicted Structural Revision," J. Am. Chem. Soc. 2012, DOI: 10.1021/ja3089394


1: InChI=1S/C15H18O3/c1-7-5-4-6-15-9(11(7)16)8-10(15)12(14(8,2)3)18-13(15)17/h5,8-10,12H,4,6H2,1-3H3/t8-,9+,10+,12+,15+/m1/s1

2: InChI=1S/C15H18O3/c1-7-5-4-6-15-9-8(10(7)16)11(15)14(2,3)12(9)18-13(15)17/h5,8-9,11-12H,4,6H2,1-3H3/b7-5-/t8-,9-,11+,12-,15+/m0/s1

NMR Steven Bachrach 05 Dec 2012 No Comments