Highly Stereoselective Decarboxylation of (+)-1-Bromo-1-chloro-2,2,2-trifluoropropanoic Acid gives (+)-1-Bromo-1-chloro-2,2,2-trifluoroethane ((+)-Halothane) with Retention of Configuration 

Olga Lavinda, David J. Szalda, Keith Ramig*

Department of Natural Sciences, Baruch College, the City University of New York, 17 Lexington Ave., New York, New York 10010

Supporting Information

Table of Contents
Nr.	Title	Page	
1.	Computational Methodology	S3	
2.	References for Computational Methodology	S4	
3.	Cartesian coordinates, number of imaginary frequencies and energies for the structures involved in the inversion of anion 10 at PCM-B3LYP/6-31++G**	S6	
4.	Cartesian coordinates, number of imaginary frequencies and energies for the structures involved in the inversion of anion 11 at PCM-B3LYP/6-31++G**	S8	
5.	Enthalpies of activation for anions 10 and 11 at PCM-B3LYP/6-31++G**, PCM-B3LYP/6-311++G** and PCM-B3LYP/aug-cc-pVDZ including Temperature parameter.	S10	

	1. Computational Methodology
	In this study, calculations were carried out using B3LYP1 hybrid functional in Gaussian092 software package using 6-31++G** basis set.  Results were confirmed with 6-311++G** and aug-cc-pVDZ basis sets. Pople’s3 6-31++G** and 6-311++G** basis sets have been shown to well reproduce experimental geometries in a range of molecules.4 Due to the presence of two sets of diffuse valence basis atomic orbitals, they satisfy the requirement for calculating anions, which calls for a use of more diffuse functions, as well as high computational efficiency.5 For comparison, the results were confirmed using Dunning’s6 aug-cc-pVDZ that was shown to overestimate the bond lengths and energies,4 but has been chosen for its consistency in anionic systems.
All stationary points were characterized as being either minima or maxima by harmonic frequency analysis. All first-order saddle points had one imaginary frequency and the local minima had zero negative frequencies. The reaction pathways were confirmed by the internal reaction coordinate (IRC)7 analysis. Reported enthalpies include unscaled zero-point energy (ZPE) corrections that were calculated with the same method and basis set. Structures reported in the manuscript were visualized using GaussView8 software.
	In attempt to reproduce experimental reactions carried out in this work, we used Polarizable Continuum Model (PCM)9 for introducing solvents. In the case of the DMPU/TEG mixture, solvent mixture was specified by using generic command alongside with PCMDoc followed by the experimental parameters, which were combined assuming linearity.10 Additionally, we included a temperature parameter in accordance with the experiment.
There exist multiple rotamers of anion 10 which differ by the position of the OMe group relative to the lone pair. In our theoretical study we considered two major conformers 10A and 10B (Fig S1) in which the position of the OMe group differs by approximately 180º. Analysis determined that 10A conformer is more stable than 10B by 3.8 kcal/mol, which is in agreement with findings of Polavarapu et al.11 who used vibrational circular dichroism for studies of 1,2,2,2,-tetrafluoroethyl methyl ether 7. They determined that trans-conformer corresponding to conformation of 10A is dominant by 78%, while the g- conformer, is less stable and is present at 22% at B3LYP/6-31G* level of theory.

Figure S1. Conformers of 211 and anion 10.

2. References for Computational Methodology
1. (a) Becke, A. D. J. Chem. Phys. 1993, 98, 1372-1377. (b) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652. (c) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785-789. (d) Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994, 98, 11623-11627.
2. Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery, Jr., J. A., Peralta, J. E., Ogliaro, F., Bearpark, M., Heyd, J. J., Brothers, E., Kudin, K. N., Staroverov, V. N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Rega, N., Millam, N. J., Klene, M., Knox, J. E., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski, J. W., Martin, R. L., Morokuma, K., Zakrzewski, V. G., Voth, G. A., Salvador, P., Dannenberg, J. J., Dapprich, S., Daniels, A. D., Farkas, Ö., Foresman, J. B., Ortiz, J. V., Cioslowski, J., Fox, D. J. (2009) Gaussian, Inc., Wallingford CT.
3. Hehre, W. J.; Random, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio Molecular Orbital Theory; Wiley: New York, 1986.
4. Wiberg, K. B.  J. Comput. Chem. 2003, 25, 1342–1346.
5. Simmons, J. J. Phys. Chem. A 2008, 112, 6401–6511.
6. Dunning, T. H., Jr. J Chem Phys 1989, 90, 1007.
7. (a) Fukui, K. Acc. Chem Res. 1981, 14, 363-368 (b) Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1990, 94, 5523-5527.
8. GaussView, Version 5, Dennington, R.; Keith, T.; Millam, J. Semichem Inc., Shawnee Mission KS, 2009.
9. Tomasi, J.; Mennucci, B.; Cammi, R. Chem. Rev., 2005, 105, 2999-3093.
10. Fox, J.; Scalmani, G. Gaussian, Inc, private communication, 2011.
11. Polavarapu, P. L.; Zhao, C.; Ramig, K. Tetrahedron: Asymmetry 1999, 10, 1099-1106.
3. Cartesian coordinates, number of imaginary frequencies and energies for the structures involved in the inversion of anion 10 at PCM-B3LYP/6-31++G**

Reactant 10

0 imaginary frequencies

 Zero-point correction=                           0.061651 (Hartree/Particle)
 Thermal correction to Energy=                    0.079033
 Thermal correction to Enthalpy=                  0.080531
 Thermal correction to Gibbs Free Energy=         0.001318
 Sum of electronic and zero-point Energies=           -590.762612
 Sum of electronic and thermal Energies=              -590.745231
 Sum of electronic and thermal Enthalpies=            -590.743732 
 Sum of electronic and thermal Free Energies=         -590.822945

-1 1
 C                  0.47053500    0.31816300   -0.48326100
 O                  1.36956700   -0.32876000    0.37367200
 C                  2.69065700   -0.44731900   -0.15160700
 H                  3.16008800    0.53703700   -0.26784100
 H                  3.26746800   -1.03625600    0.56734200
 H                  2.67838800   -0.95562300   -1.12296700
 C                 -0.88791000   -0.17306500   -0.06366700
 F                 -1.05729900   -1.48933700   -0.39719000
 F                 -1.89426200    0.51454600   -0.68171400
 F                 -1.21425900   -0.11367800    1.28850400
 F                  0.42113400    1.74383100    0.01543300

Transition State 10 – -elimination
(Displacement vectors show direction of atom movement during elimination)

1 imaginary frequency

Zero-point correction=                           0.060735 (Hartree/Particle)
 Thermal correction to Energy=                    0.077861
 Thermal correction to Enthalpy=                  0.079359
 Thermal correction to Gibbs Free Energy=         0.000022
 Sum of electronic and zero-point Energies=           -590.751326
 Sum of electronic and thermal Energies=              -590.734199
 Sum of electronic and thermal Enthalpies=            -590.732701 
 Sum of electronic and thermal Free Energies=         -590.812038

-1 1
 C                  0.48574000    0.35301600   -0.20944300
 F                 -1.66377200   -0.22483400    1.33909300
 F                 -1.75220300    0.59293600   -0.84359400
 F                 -0.95957300   -1.44600300   -0.53116500
 F                  0.53328400    1.74832000    0.06572900
 O                  1.42458300   -0.32460400    0.51943300
 C                  2.68486800   -0.50411100   -0.15013100
 H                  3.15500200    0.46278000   -0.35903700
 H                  3.31901200   -1.07793700    0.52925800
 H                  2.54441800   -1.05452100   -1.08642900
 C                 -0.80972900   -0.14344700   -0.22539600

4. Cartesian coordinates, number of imaginary frequencies and energies for the structures involved in the inversion of anion 11 at PCM-B3LYP/6-31++G**

Reactant 11

0 imaginary frequencies

Zero-point correction=                           0.018647 (Hartree/Particle)
 Thermal correction to Energy=                    0.028576
 Thermal correction to Enthalpy=                  0.029735
 Thermal correction to Gibbs Free Energy=        -0.024691
 Sum of electronic and zero-point Energies=          -3407.760724
 Sum of electronic and thermal Energies=             -3407.750795
 Sum of electronic and thermal Enthalpies=           -3407.749636 
 Sum of electronic and thermal Free Energies=        -3407.804062

-1 1
 C                 -0.14916900    0.34727100   -0.70214700
 Cl                -0.43009800    2.03573600    0.01542000
 Br                 1.64029100   -0.27960400    0.00727800
 C                 -1.17023600   -0.54295800   -0.05068300
 F                 -1.24831700   -0.60972100    1.33417300
 F                 -1.00642500   -1.83783800   -0.45009900
 F                 -2.43215400   -0.17991600   -0.43961700

30º Rotamer of Anion 11
(Displacement vectors show direction of atom movement during rotation of CF3)

0 imaginary frequencies

Zero-point correction=                           0.018462 (Hartree/Particle)
 Thermal correction to Energy=                    0.030531
 Thermal correction to Enthalpy=                  0.031838
 Thermal correction to Gibbs Free Energy=        -0.033827
 Sum of electronic and zero-point Energies=          -3407.754169
 Sum of electronic and thermal Energies=             -3407.742101
 Sum of electronic and thermal Enthalpies=           -3407.740793
 Sum of electronic and thermal Free Energies=        -3407.806458

-1 1
 C                 -0.12908300    0.35813000   -0.62868500
 Cl                -0.38261000    2.05116100    0.01791700
 Br                 1.65899500   -0.30654100    0.00520900
 C                 -1.19844800   -0.52849500   -0.05897900
 F                 -0.81305200   -1.82741100    0.06118700
 F                 -2.31564100   -0.51853100   -0.86015400
 F                 -1.71522700   -0.22279500    1.20330700

Transition State – inversion of asymmetric carbon in anion 11
(Displacement vectors show direction of atom movement during inversion)

1 imaginary frequency

Zero-point correction=                           0.017755 (Hartree/Particle)
 Thermal correction to Energy=                    0.027240
 Thermal correction to Enthalpy=                  0.028399
 Thermal correction to Gibbs Free Energy=        -0.025456
 Sum of electronic and zero-point Energies=          -3407.743089
 Sum of electronic and thermal Energies=             -3407.733605
 Sum of electronic and thermal Enthalpies=           -3407.732446
 Sum of electronic and thermal Free Energies=        -3407.786301

-1 1
 Cl                 0.27481000    2.07284700    0.00003200
 C                  0.06940400    0.32187900    0.00043800
 Br                -1.70193300   -0.35262600    0.00001500
 C                  1.20674100   -0.48797600   -0.00006000
 F                  2.15271800   -0.30416300   -1.08604500
 F                  2.15291000   -0.30527400    1.08625300
 F                  0.94315200   -1.82388700   -0.00057700

5. Enthalpies of activation for anions 10 and 11 at PCM-B3LYP/6-31++G**, PCM-B3LYP/6-311++G** and PCM-B3LYP/aug-cc-pVDZ including Temperature parameter.

	B3LYP /6-31++G**	B3LYP/6-311++G**	B3LYP/aug-cc-pVDZ	
10 H≠elimination	6.35 kcal/mol	5.29 kcal/mol	6.24 kcal/mol	
11 H≠ inversion	10.23 kcal/mol	10.01 kcal/mol	11.24 kcal/mol