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Guidelines for Computational Experiment Reports Your report must be typed (Arial Regular Font Size 12, 1.5 line spacing, right justified) with numbered pages using ChemDraw equations and structures, Microsoft Word, relevant Gaussian optimized structures, Figures, data tables and other Important information from your calculations. HOMOs, LUMOs, and electrostatic potential maps must be in color. Your report will demonstrate and show your unique analytical skills, brilliance, creativity, and understanding of the concepts and mechanisms in the experiment you have investigated. Title of Experiment Using ChemDraw write a balanced equation for your reaction. Also use ChemDraw to prepare a Scheme (Figure) using traditional arrow pushing to show the currently accepted mechanism(s) for the reaction. 1 Chem 138 AN INTRODUCTION TO COMPUTATIONAL ORGANIC CHEMISTRY Your Name Spring 2021 Title: Tutorial 1: A Computational Mechanistic Study of the Nucleophilic Substitution Reaction (SN2) of Fluoride Anion and Chloromethane in the Gas Phase Abstract The mechanism of the SN2 reaction of fluoride anion with chloromethane 1 to give fluoromethane 2 and chloride anion in the gas phase was studied at the second order M?ller-Plesset MP2/6-311++G(d,p) level of theory. The reaction pathway involves reactants R, a reactant complex RC (ion dipole or ion-molecule), a bimolecular transition structure TS, a product complex PC (ion dipole or ion-molecule) and products Pr. The activation( thermodynamic) parameters for the reaction mechanism were calculated and elucidated. Keywords (include at least four words) Activation parameters; Backside attack; Bimolecular reaction; Inversion of configuration; Ion molecule complex; Leaving group; Nucleophilic attack; Pentacoordinate carbon; Stereospecific reaction; Substitution reaction; Walden inversion Introduction and Objectives The SN2 reaction is one of the most important reactions in chemistry. In addition to the traditional SN2 mechanism undergraduates generally study in organic chemistry with the nucleophile attacking the carbon at the opposite side of the leaving group leading to a bimolecular transition structure TS, many other mechanisms have been proposed (see page 3 below).1-8 In this mechanistic study we will explore the influences of ion dipole complexes in the reaction of fluoride anion with chloromethane 1 to give fluoromethane 2 2 in the gas phase. The thermodynamic parameters for the mechanism will be calculated and analyzed. See Reference 3 3 Examples of the gas phase SN2 mechanisms are shown in the potential energy profile diagrams below. Ion dipole complexes (reactant complexes, RC) in which the nucleophile and neutral reactant (R) are weakly bound.(see the double-well energy profile curves below). The RC leads to the transition structure TS that connects (IRC calculations) RC to the product complex PC that subsequently affords the separated products Pr. You must design an original diagram that is consistent with your calculated mechanism. See Reference 5- See Reference 4 4 Computational Methods Calculations were performed with the Gaussian 16 computational programs using the MP2/6-311++G(d,p) level of theory.11-13 No constraints were imposed on the structures in the equilibrium geometry optimizations and in the transition structure optimizations. Vibrational frequency analyses were carried out in order to assess the nature of the stationary points and to obtain zero-point energies, enthalpies, entropies, and free energies. The characteristics of local minima and transition states were verified by establishing that the former did not have an imaginary frequency and that the latter had only one imaginary frequency. Intrinsic reaction coordinate (IRC) calculations were used to connect the transition state structures TS to the reactants R, reactant complexes RC, product complexes PC, and products Pr. The charge distributions were analyzed using the Mulliken population analysis.12 Results and Discussion Briefly discuss the results and significance of your calculations including charges, ChemDraw structures, energy profile diagrams, equations, Figures, graphs, IRC plots, optimized structures, properties of reactants, products, and transitions structures, 5 spectroscopy, tabulated , thermochemical data, relative energies, and other scientific data to support your computed results, your conclusions, your explanations, and your mechanisms. In logical order reconcile your calculated results in the Tables below with your energy profile diagram. Table 1. Energies of the Separated Reactants (CH3Cl 1 + F–) and the Ion Molecule Reactant Complex (F–---CH3Cl) RC CH3Cl 1 F– CH3Cl 1 + F– RC ?RCc F–---CH3Cl point groupa C3v chargeb Oh -1 dipole moment 2.2 bond distance C-Cl 1.776 C3v -1 -1 0.0 9.1 C-Cl 1.825 C-F 2.617 enthalpy H -499.386389 -99.676326 -599.062715 -599.084928 -13.939 free energy G -499.412921 -99.692845 -599.105765 -599.119377 -8.52 55.840 34.767 90.607 Energyelectronic -499.428839 -99.678687 -599.107526 -599.129816 -13.987 Eelect+ZPVE -499.390322 -99.678687 -599.069009 -599.091203 -13.927 entropy S aMP2/6-311++G(d,p) 72.505 -18.102 optimized structures. bMulliken charge distributions for CH3Cl 1 H 0.165; C -0.528; Cl 0.033 and reactant complex RC H 0.195; C -0.539; Cl -0.114; F0.931. cEnergy difference between column 5 and column 6 times 627.51 to convert hartrees to kcal/mol. 6 Table 2. Energies of Separated Reactants (CH3Cl 1 + F–) and the Transition Structure [F---CH3---Cl]‡ TS CH3Cl 1 F– 1 + F– TS ?TSc [F---CH3---Cl]‡ point groupab C3v charge Oh -1 dipole moment 2.2 bond distance C-Cl 1.785 C3v 560i -1 -1 0.0 3.1 C-Cl 2.149 C-F 1.986 enthalpy H -499.386389 -99.676326 -599.062715 -599.074054 free energy G -499.412920 -99.692845 -599.105765 -599.104990 entropy S 55.840 34.767 90.607 65.110 Energyelectronic -499.428839 -99.678687 -599.107526 -599.117770 Eelect+ZPVE -499.390322 -99.678687 -599.069009 -599.079331 aMP2/6-311++G(d,p) optimized structures and bMulliken charge distributions for CH3Cl 1 H 0.165; C -0.528; Cl -0.033; transition structure TS H 0.184; C -0.261; Cl -0.520; F -0.772. 7 Table 3. Energies of Separated Reactants (CH3Cl 1 + F–) and the Ion-Molecule Product Complex (F---CH3---Cl) PC CH3Cl 1 F– 1 + F- PC ?PCc F---CH3---Cl point groupab charge C3v Oh 0 -1 C3v -1 -1 dipole moment 2.0 6.3 bond distance C-Cl 1.785 C-Cl 3.203 C-F 1.419 enthalpy H -499.952441 -99.807148 -599.759589 -599.119998 free energy G -499.979014 -99.823668 -599.802682 -599.153787 entropy S 55.927 34.767 90.694 71.115 Energyelectronic -499.994265 -99.809509 -599.803693 -599.166458 Eelect+ZPVE -499.956399 -99.809509 -599.803693 -599.126076 aMP2/6-311++G(d,p) optimized structures and bMulliken charge distributions for product complex PC: H 0.154 C -0.193; Cl -0.942; F -0.328. 8 Table 4. Energies of Separated Reactants (CH3Cl 1 + F– ) and Separated Products (F–CH3 2 + Chloride Anion) CH3Cl 1 + F– point groupab charge -1 dipole moment F–CH3 2 Cl– C3v Oh 0 -1 1.9 0 F–CH3 + Cl– -1 bond distance enthalpy H -599.759589 -139.638072 -460.174552 -599.812624 free energy G -599.802682 -139.663346 -460.191935 -599.855281 53.193 36.586 89.779 entropy S 90.694 Energyelectronic -599.803693 -139.681154 -460.176912 -599.858066 Eelect+ZPVE -599.803693 -139.641927 -460.176912 -599.818839 aMP2/6-311++G(d,p) optimized structures. bMulliken charge distributions for the product fluoromethane 2 H 0.136; C -0.115; F -0.294. 9 References 1. Foresman, J. B.; Frisch, A. Exploring Chemistry with Electronic Methods 3rd Edition, pages 271-274,Gaussian, Inc., Wallingford, CT 2015. 2. Shi, Z.; Boyd, R. J. Transition-State Electronic Structures in SN2 Reactions. J. Am. Chem. Soc. 1989, 111, 1575-1579. 3. Xie, J.; Hase, W. I. Rethinking the SN2 Reaction. Science 2016 352, 32-33. 4. Vayner, G.; Houk, K. N.; Jorgensen, W. L.; Brauman, J. I. Steric Retardation of SN2 Reactions in the Gas Phase and Solution. J. Am. Chem. Soc. 2004, 126, 90549058. 5. Li, Q.-G.; Xu, K.; Ren, Y. Origin of Enhanced Reactivity of Microsolvated Nucleophile in Ion Pair SN2 Reactions: The Cases of Sodium p-Nitrophenoxide with Halomethanes in Acetone. J. Phys. Chem. A 2015, 119, 3878-3886. 6. Angel, L. A.; Ervin, K. M. Dynamics of the Gas-Phase Reactions of Fluoride Ions with Chloromethane. J. Phys. Chem. A 2001, 105, 4042-4051. 7. Szabó, I.; Czakó, G. Benchmark ab Initio Characterization of the complex Potential Energy Surface of the Cl- + CH3I Reaction. J. Phys. Chem. 2017, 121 5748-5757. 8. Xxxxx 9. Xxxxx 10. Xxxxx 11. Gaussian 16, Revision B.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Petersson, G. A.; Nakatsuji, H.; Li, X.; Caricato, M.; Marenich, A. V.; Bloino, J.; Janesko, B. G.; Gomperts, R.; Mennucci, B.; Hratchian, H. P.; Ortiz, J. V.; Izmaylov, A. F.; Sonnenberg, J. L.; Williams-Young, D.; Ding, F.; Lipparini, F.; Egidi, F.; Goings, J.; Peng, B.; Petrone, A.; Henderson, T.; Ranasinghe, D.; Zakrzewski, V. G.; Gao, J.; Rega, N.; Zheng, G.; Liang, W.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Throssell, K.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M. J.; Heyd, J. J.; Brothers, E. N.; Kudin, K. N.; Staroverov, V. N.; Keith, T. A.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A. P.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Millam, J. M.; Klene, M.; Adamo, 10 C.; Cammi, R.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Farkas, O.; Foresman, J. B.; Fox, D. J. Gaussian, Inc., Wallingford CT, 2016. 12. Mulliken, R. S. Electron Population Analysis on LCAO-MO Molecular Wave Functions II J. Chem. Phys. 1955, 23, 1833-40, DOI: 10.1063//1.1740588. 13. Freeman, F. Archives Chem 138 Chem. Dept. Univ. of California, Irvine, CA 92697. 11 Supporting Information 12 Computational and Theoretical Chemistry 1098 (2016) 13–21 Contents lists available at ScienceDirect Computational and Theoretical Chemistry journal homepage: www.elsevier.com/locate/comptc A computational study on the reaction mechanism and energetics of Markovnikov and anti-Markovnikov addition in alkyne hydrothiolation reactions Elambalassery G. Jayasree ⇑, Sobhana Reshma Department of Chemistry, University of Kerala, Kerala 695581, India a r t i c l e i n f o Article history: Received 6 July 2016 Received in revised form 16 October 2016 Accepted 16 October 2016 Available online 17 October 2016 Keywords: Alkyne hydrothiolation Vinyl sulfides Markovnikov Radical catalyzed pathway a b s t r a c t The present work provides a deep insight into the mechanistic and energetic aspects of alkyne hydrothiolation reaction. This work can be regarded as the first ever computational attempt to unravel the reaction pathway under transition metal free conditions. The results confirmed a concerted pathway for uncatalyzed gas phase reactions. Reduced natural charge analysis pointed out that the characterized transition structures could be envisaged as a hypothetical ion pair, the stabilization of which led to reduced energy barriers. Hydroxyl radical catalyzed pathway was unraveled for the reaction which was then compared with the uncatalyzed reactions in terms of energy barrier and the feasibility of the mode of addition. The catalyzed reaction was also marked for its high degree of regioselectivity, leading to an unselective mixture of (E/Z) anti-Markovnikov products. Ó 2016 Elsevier B.V. All rights reserved. 1. Introduction Vinyl sulfides find potent applications as synthetic intermediates in general organic synthesis, in pharmaceutical industry as well as in material sciences [1–9]. Thus, efficient, atom economic and green procedures for the synthesis of vinyl sulfides are of great scientific interest these days [1,2,10–12]. Synthesis of vinyl sulfides can be achieved via two major approaches- cross coupling and addition reactions. The former being a substitution reaction, does not proceed with 100% atom efficiency, however converse is the case with addition reactions [9,10]. Both the atom economic nature [13–17] and the ease of availability of alkynes over the corresponding vinyl halides make the addition reactions more prominent over cross coupling [10,18]. Addition of thiols to alkynes can possibly lead to the formation of Markovnikov as well as (E/Z) anti-Markovnikov products (Scheme 1). However the reaction when carried out under thermal, photochemical or basic conditions resulted in a mixture of (E/Z) anti-Markovnikov species [3,7,19–22]. In recent years transition metal mediated pathway for the reaction has impressively taken over other methodologies in order to strive for remarkable selectivity and atom efficiency [2,19]. A key factor that aided this emergence was the overcoming of the established belief about sulfur compounds being catalytic poisons [2,23]. Even though it paved ⇑ Corresponding author. E-mail address: jelambal@gmail.com (E.G. Jayasree). http://dx.doi.org/10.1016/j.comptc.2016.10.012 2210-271X/Ó 2016 Elsevier B.V. All rights reserved. the way for varied catalyzed studies on these reactions, catalyst with good regio- and stereoselectivity still remains elusive. This demands an in-depth study of exploring and analyzing the mechanistic pathway of this reaction in various environments such as gas phase, photochemical or basic conditions which has been anticipated to provide with details to assist in the fine tuning of a better regio- and stereoselective catalyst. The current study, thus, aims at exploring computationally the different possible pathways through which the uncatalyzed reaction proceeds. These results will then be compared with the experimentally reported radical catalyzed reaction by unraveling its mechanism computationally. Detailed analysis of the reaction coordinate would enable to trace out the various electronic and steric reasons that control the regio- and stereoselectivity of the lowest energy pathway. 2. Computational methods Characterization of the different reaction points of alkyne hydrothiolation has been carried out using molecular orbital theory program package, Gaussian 09 [24] and the visualization tool, Gauss view 5.0 [25]. The gas phase reaction mechanisms have been investigated at MP2/6-311++G(d,p)//B3LYP/6-31+G(d) level for a series of substituted acetylenes and thiols [26,27]. The reactants employed in the study and their labels used in the discussion are given in Table 1. 14 E.G. Jayasree, S. Reshma / Computational and Theoretical Chemistry 1098 (2016) 13–21 R R 'S H R'S R + R Markovnikov + R 'S R R'S E- anti -Markovnikov Z-anti-Markovnikov Scheme 1. Alkyne hydrothiolation reaction resulting in Markovnikov as well as Z and E anti-Markovnikov products. Table 1 The reactants employed in the study and their labels. Acetylene and its analogues a Substituted thiols Systems Labels used Systems Labels used (1) (2) (3) (4) (5) (6) HCCH MeCCH MeCCMe VinylCCH MeCCVinyl VinylCCVinyl (1) (2) (3) (4) (5) (6) MeSH EtSH VinylSH AllylSH C5H5SHa PhSH Acetylene Propyne But-2-yne Vinylacetylene Methylvinylacetylene Divinylacetylene Methanethiol Ethanethiol Vinylthiol Allylthiol Cyclo-Pentadienethiol Thiophenol In the case of C5H5SH, the point of attachment of C5H5 to ASH group is at the CH2 carbon atom. All the computed reaction points were confirmed by performing vibrational frequency analysis. The geometry of the concerted transition structure was characterized by having one imaginary vibrational frequency and confirmed by Intrinsic Reaction Coordinate (IRC) analysis. Natural bond orbital analysis (NBO) was performed to study the natural charge developed on the transition structures [28]. In the case of radical catalyzed reactions, precautions have been adopted via ensuring that hS2i value is not higher than 0.75 for all the characterized reaction points. 3. Results and discussion Two possible addition pathways, viz. concerted (Scheme 2a) and multistep can be proposed for the addition of thiols to alkyne. Multistep pathway can proceed through initial thiolate attack on alkyne followed by thiolic H attack or vice versa (Scheme 2b and c respectively). Various theory methods such as HF [29], B3LYP, M06-2X [30] and MP2 at 6-31+G(d) level were employed to investigate these reaction pathways for the reaction system HCCH + MeSH. The concerted pathway (Scheme 2a) could be traced out computationally by all these methods. Even though HF/6-31+G(d) could locate all the reaction points corresponding to the multistep pathway involving initial thiolate attack (Scheme 2b), none of the aforementioned higher level methods could characterize the entrance TS or the subsequent reaction points of both the multistep pathways. Thus the proposed multistep reaction pathways could be ruled out favoring only the concerted pathway. The computed reaction points for the concerted pathway in gas phase are shown below (Fig. 1). Concerted addition of thiol to alkyne involves the formation of a reaction complex initially. The TS has been computed to have elongated acetylenic C„C and thiol SAH bonds. The computed bond length values of the reactants and the TS clearly indicate this change. The C„C and SAH bond lengths in the reactants, HCCH and MeSH are 1.208 Å and 1.351 Å respectively while in the TS the respective values changes to 1.259 Å and 1.827 Å (Fig. 1 and Table 2). The C„C and SAH Wiberg Bond Index (WBI) values in the reactants, HCCH and MeSH are 2.996 and 0.967 respectively and in the computed TS (Fig. 1) the respective values are 2.358 and 0.348. The lowering of the WBI values which is a measure of bond strength points out weakening of the respective bonds. The geometrical parameters of the TS also point out the partial bond formation of C1AS6 and C3AH2. The distances of these newly forming C1AS6 and C3AH2 bonds in the TS are 2.791 Å and 1.228 Å respectively (Fig. 1 and Table 2) while those in the product are 1.772 Å and 1.087 Å respectively. The corresponding WBI values in the TS are 0.553 and 0.575 respectively while those in the product are 1.085 and 0.924 respectively. These bond lengths and WBI values suggest that SAH bond is almost broken and C3AH2 bond is nearly formed in the TS. On comparing the natural charges of computed TS with reactants, it has been found that the acetylenic C1 becomes more positive (from 0.234 to 0.245) and thiolic S becomes more negative (from 0.068 to 0.189) while C3 and H2 do not show any marked changes (Tables 2 and 3). This together with bond length values of C1AS6 and C3AH2 made the TS to be envisaged as a hypothetical ion pair (Scheme 3) involving thiolate anion and protonated acetylene. The energetics of this concerted reaction pathway has been studied by computing the energy barrier values (Table 4). Both the energy barrier values were calculated as the energy difference between the TS and RC (DE⁄) and between TS and reactants (DE). The respective values computed for HCCH + MeSH reaction system are 63.59 and 60.75 kcal/mol. The study has then been extended to various reaction systems involving substituted acetylenes, R1CCR2 (R1 and/or R2 = H, Me, Vinyl) and various thiols R3SH (R3 = Me, Et, Vinyl, Allyl, C5H5, Ph). The reaction points of concerted mechanism for two systems, viz. E.G. Jayasree, S. Reshma / Computational and Theoretical Chemistry 1098 (2016) 13–21 15 Scheme 2. Proposed concerted and multistep pathways. HCCH + MeSH and MeCCH + MeSH (Markovnikov mode addition) were computed in three methods- MP2, M06-2X and B3LYP using 6-31+G(d) basis set. It was found that the reaction between MeCCH and MeSH is more feasible in all three methods and difference in energy barrier between the two systems remains more or less the same in all three methods (3 kcal/mol). Since B3LYP is the inexpensive and widely used computational method among these three it has been employed for all other computations and for better energetic considerations, single point calculations were performed at MP2/6-311++G(d,p). Symmetrical alkynes would lead to the formation of a product as in the case of HCCH + MeSH reaction system while unsymmetrical alkynes would lead to the formation of Markovnikov and anti-Markovnikov addition products (Scheme 1). In the case of reaction systems of symmetrical alkynes including HCCH, the computed TS has been shown to have more elongated C1AC3 and S6AH2 bonds with PhSH and VinylSH (Table 2). Besides C3AH2 bonds were comparatively more formed with these thiols. However, C1AS6 bond shows more elongation. It has also been found that these systems have low energy barrier values within the particular alkyne series (Table 4). These geometrical changes and low energy barrier values support the ion-pair TS argument. The near to complete C3AH2 bond formation and partially formed C1AS6 bond indicate thiolate anion-protonated alkyne ion pair TS. Identical geometrical changes were computed for reaction systems involving unsymmetrical alkynes that leads to both Markovnikov 16 E.G. Jayasree, S. Reshma / Computational and Theoretical Chemistry 1098 (2016) 13–21 Fig. 1. Optimized reaction points of concerted reaction pathway (MP2/6-311++G(d,p)//B3LYP/6-31+G(d)); The relative energy values with respect to sum of the energies of P reactants ( E(HCCH + MeSH)) in kcal/mol are given for each reaction point. Table 2 The computed bond lengths and reduced natural charges on the TS involving HCCH and MeCCH with different thiols. The numberings are taken from Fig. 1. Systems Reduced natural charges on Bond lengths (Å) C1 S6 C3 H2 C1AC3 S6AH2 C3AH2 C1AS6 TS(HCCH + MeSH) TS(HCCH + EtSH) TS(HCCH + VinylSH) TS(HCCH + AllylSH) TS(HCCH + C5H5SH) TS(HCCH + PhSH) 0.245 0.246 0.244 0.250 0.236 0.234 0.189 0.183 0.162 0.174 0.152 0.136 0.202 0.203 0.212 0.200 0.202 0.213 0.244 0.245 0.246 0.244 0.241 0.243 1.259 1.259 1.263 1.259 1.260 1.263 1.827 1.831 1.888 1.820 1.833 1.884 1.228 1.227 1.201 1.232 1.224 1.202 2.791 2.797 2.905 2.793 2.815 2.906 Markovnikov addition TS(MeCCH + MeSH) TS(MeCCH + EtSH) TS(MeCCH + VinylSH) TS(MeCCH + AllylSH) TS(MeCCH + C5H5SH) TS(MeCCH + PhSH) 0.244 0.246 0.248 0.250 0.242 0.243 0.262 0.256 0.228 0.249 0.224 0.203 0.215 0.215 0.219 0.212 0.212 0.220 0.261 0.262 0.263 0.261 0.259 0.261 1.264 1.265 1.267 1.264 1.265 1.267 1.874 1.880 1.933 1.869 1.877 1.925 1.198 1.196 1.178 1.200 1.196 1.180 2.894 2.901 2.996 2.904 2.912 2.996 Anti-Markovnikov addition TS’(MeCCH + MeSH) TS0 (MeCCH + EtSH) TS0 (MeCCH + VinylSH) TS0 (MeCCH + AllylSH) TS0 (MeCCH + C5H5SH) TS0 (MeCCH + PhSH) 0.248 0.249 0.249 0.253 0.241 0.240 0.210 0.204 0.183 0.196 0.171 0.157 0.279 0.280 0.287 0.278 0.277 0.286 0.258 0.259 0.260 0.258 0.255 0.258 1.261 1.261 1.264 1.261 1.262 1.264 1.830 1.834 1.888 1.822 1.830 1.881 1.227 1.226 1.202 1.231 1.225 1.204 2.763 2.769 2.868 2.765 2.776 2.864 and anti-Markovnikov products as well. Table 2 provides the geometrical parameters of reaction systems MeCCH + R3SH where all other values are given in the supplementary material. An analysis on the reduced natural charges of TS indicates that the stabilization of charges on S6 in comparison to the HCCH + MeSH reaction system leads to reduced energy barriers. Accordingly if the group R3 in the TS (Scheme 3) can stabilize the negative charge on the thiolate ion, that should lead to lowering of energy barrier and that was the result obtained upon computation. For example across a particular acetylene series, significant resonance stabilization of the thiolate ion in the TS involving PhSH led to lowered energy barrier [DE⁄ of TS(HCCH + MeSH) and TS E.G. Jayasree, S. Reshma / Computational and Theoretical Chemistry 1098 (2016) 13–21 Table 3 The computed natural charges on different thiols in gas phase. Systems Natural charges on MeSH EtSH VinylSH AllylSH C5H5SH PhSH S H 0.068 0.065 0.005 0.065 0.027 0.036 0.138 0.135 0.146 0.139 0.138 0.144 R2 R2 C1 S C3 H R3 C1 δ C3 R1 S R3 Hδ R1 Scheme 3. TS as a hypothetical ion pair. Table 4 Computed DE and DE⁄ values for the addition of various substituted thiols to HCCH in gas phase. The deviation in energy barrier from the parent system HCCH + MeSH is given in parentheses. Systems HCCH series HCCH + MeSH HCCH + EtSH HCCH + VinylSH HCCH + AllylSH HCCH + C5H5SH HCCH + PhSH DE⁄ = ETS ERC, while DE = ETS MP2/6-311++G(d,p)//B3LYP/6-31 + G(d) DE⁄ (kcal/mol) DE (kcal/mol) 63.59 63.41 60.68 62.82 60.61 57.33 60.75 60.71 58.20 59.04 57.31 54.74 (0.00) (0.18) (2.91) (0.77) (2.98) (6.26) P Ereactants. (0.00) (0.04) (2.55) (1.71) (3.44) (6.01) 17 (HCCH + PhSH) are 63.59 and 57.33 kcal/mol respectively (Table 4)]. This can be attributed to the resonance stabilization of the corresponding transition structure (Scheme 4). It is clear from the scheme that the negative charge on S atom is delocalized over the ring carbons thereby leading to a stabilized thiolate ion. This can be justified by the comparatively lowest natural charge computed on S atom (0.136) in this TS (Table 2). TS involving C5H5SH has the second lowest energy barrier which can be attributed to the next stabilized negative charge computed on S6 (Tables 2 and 4). TS involving VinylSH has the next lowest energy barrier that also corresponds to low computed negative charge on S (Table 4). This trend has been reproduced for all the investigated unsymmetrical alkynes leading to both Markovnikov and antiMarkovnikov product as well. Similarly in the TS (Scheme 3), if the group R2 is capable of stabilizing the positive charge developed on the C1 acetylenic carbon (to which S attacks) then the energy barrier should be lowered. The energy barriers, DE⁄ values of the reactions corresponding to TS (HCCH + PhSH) and Markovnikov TS(MeCCH + PhSH) are 57.33 kcal/mol and 56.45 kcal/mol respectively (Tables 4 and 5). Here the +I effect of Me group should stabilize the charge on C1 though not reflected in the computed reduced natural charges. Mesomeric effect of vinyl group in conjugation with the acetylenic triple bond has the effect of lowering energy barrier via charge stabilization (reduced natural charge on C1 for VinylCCH + PhSH system is 0.180, which is stabilized in comparison to the respective charge on HCCH + PhSH system, Table 2) [DE⁄ of (HCCH + PhSH) and (VinylCCH + PhSH) are 57.33 and 55.40 kcal/mol respectively]. On comparing the effect of Me and Vinyl group in lowering the energy barrier, it becomes clear that mesomeric effect dominates inductive effect. To further validate the role of the R2 group, transition structures with R2 = AOH and ANH2 were characterized. The concerned energy barriers were found to be lowered as compared to HCCH + PhSH system, i.e., in the case of TS(HCCH + PhSH), DE⁄ = 57.33 kcal/mol, whereas in the case of (H2NCCH + PhSH) and (HOCCH + PhSH) the corresponding energy barriers are 42.28 and 50.72 kcal/mol respectively. When electron withdrawing substituents such as ACF3 and ACl were attached to C1, the energy Scheme 4. 18 E.G. Jayasree, S. Reshma / Computational and Theoretical Chemistry 1098 (2016) 13–21 Table 5 Computed DE and DE⁄ values for the Markovnikov and anti-Markovnikov addition of various substituted thiols to unsymmetrical MeCCH in gas phase. The deviation in energy barrier from the MeCCH + MeSH reaction system is given in parentheses. Systems MP2/6-311++G(d,p)//B3LYP/6-31 + G(d) DE⁄ (kcal/mol) DE (kcal/mol) Markovnikov addition MeCCH series MeCCH + MeSH MeCCH + EtSH MeCCH + VinylSH MeCCH + AllylSH MeCCH + C5H5SH MeCCH + PhSH 62.51 62.39 59.58 62.05 59.45 56.45 DE⁄ = ETS ERC, while DE = ETS (0.00) (0.12) (2.93) (0.46) (3.06) (6.06) DE⁄ (kcal/mol) DE (kcal/mol) Anti-Markovnikov addition 59.99 60.01 57.46 58.17 56.59 54.08 (0.00) (0.02) (2.53) (1.82) (3.40) (5.91) 64.42 64.28 61.61 63.99 61.19 58.34 (0.00) (0.14) (2.81) (0.43) (3.23) (6.08) 61.90 61.89 59.49 60.11 58.32 55.97 (0.00) (0.01) (2.41) (1.79) (3.58) (5.93) P Ereactants. barrier values (DE⁄ values are 54.23, 54.91 kcal/mol respectively) were found to be increased as compared to the case with electron donating groups, but when compared to HCCH + PhSH system, the energy barriers are still lower. C3 has got a slight negative charge, stabilization of which favors the reaction moderately. Since the bond length analysis of TS revealed that the C3AH2 bond is almost formed, the effect of electron donating groups on C3 will have only diminished effects on the DE⁄ values as compared to that on C2. On comparing DE⁄ values of the systems HCCH and MeCCH (Me on C3, anti-Markovnikov case) it becomes clear that +I effect of Me destabilizes the charge on C3 thus leading to moderately increased energy barrier [DE⁄ of (HCCH + PhSH) and (MeCCH + PhSH) are 57.33 and 58.34 kcal/mol respectively (Tables 4 and 5)]. Similarly on comparing MeCCH + PhSH-Markovnikov addition (56.45 kcal/mol) and MeCCMe + PhSH (56.97 kcal/mol) systems it becomes clear that +I effect of Me on C3 is not so influential. Electron donating groups such as ANH2 and AOH as R1 destabilizes the charge on C3, thereby increasing the energy barrier in comparison to HCCH + PhSH system (DE⁄ values are 59.44 and 59.70 kcal/mol respectively). Similarly electron withdrawing substituents such as ACF3 and ACl on C3 have been found to decrease the energy barrier values (DE⁄ values are 53.70, 55.90 kcal/mol respectively). Thus, in Fig. 2. Concerted trans addition TS. general, it can be concluded that any factor that stabilize the ion pair would favor the reaction. As mentioned earlier, the cis addition pathway leading to E-anti-Markovnikov products for the unsymmetrical alkynes with the various substituted thiols were unraveled and energetics were also analyzed (Table 5). By comparing the Markovnikov’s and E-anti-Markovnikov’s addition reactions, it has been found that most of the computed systems favor Markovnikov product formation. Small energy difference between the two makes the E-anti-Markovnikov product formation also a feasible reaction. Concerted trans addition of thiol to alkyne involves the attack of the thiolic hydrogen to one of acetylenic carbon atom in a trans manner along with the sulfur attack on the other carbon. Such a transition structure for HCCH + MeSH reaction has been computed (Fig. 2) and the result leads to a high energy barrier (9.63 kcal/mol greater than that for the cis case). The concerted trans TS employing other acetylene analogues were not attempted further due to this high energy barrier. Literature reports showed that base or radical catalyzed reaction proceeds in favor of the (E/Z) anti-Markovnikov products [19,21]. Thus a radical catalyzed multistep pathway has been computationally explored here as an attempt to look at the energy barrier in comparison to uncatalyzed gas phase reactions. Proposed reaction mechanism involves initiation by a hydroxyl radical that abstracts a hydrogen free radical from ASH group of thiol. Thus generated methane thiyl radical triggers the addition reaction by attacking on one of the acetylenic carbon. Finally a water molecule comes in, thus separating the product with the regeneration of the catalyst. The characterized reaction points (at MP2/6-311++G(d,p )//B3LYP/6-31+G(d) level) are shown in Fig. 3. The entrance TS, TS1 (Fig. 3) corresponds to thiol activation by a hydroxyl radical. The single imaginary frequency of 669.45 cm1 and elongated thiol SAH bond length of 1.396 Å (WBI = 0.189) indicates that hydrogen free radical is getting abstracted from thiol molecule (the computed SAH bond distance in MeSH is 1.351 Å, WBI = 0.967). This step corresponds to an energy barrier of 4.46 kcal/mol. It is evident from the energy barrier values that the next step involving the thiyl addition to the acetylenic carbon (TS2) is the rate determining step for the concerned radical catalyzed reaction (see Fig. 4), where the single imaginary frequency of -534.38 cm1 depicts the CAS bond formation. In the exit TSTS3, an elongated OAH bond length (1.215 Å, WBI = 0.135) in water indicates its tendency to break and a new CAH bond has been started forming (1.294 Å, WBI = 0.087) leading to the desired product, vinyl sulfide (actual computed OAH bond distance in H2O and CAH bond distance in vinyl sulfide are 0.969 Å (WBI = 0.758) and 1.090 Å (WBI = 0.924) respectively). An energy barrier of 21.39 kcal/mol has been computed for this step. In order to get an idea about the regio- and stereoselectivity of this particular pathway, the TS corresponding to the rate determin- E.G. Jayasree, S. Reshma / Computational and Theoretical Chemistry 1098 (2016) 13–21 19 Fig. 3. Hydroxyl radical catalyzed alkyne hydrothiolation reaction of HCCH and MeSH and the corresponding energy barrier values. Fig. 4. Energy profile diagram for the radical catalyzed pathway is shown. Here zero energy value is assigned to the sum of energy of all 5 moieties present in the catalytic cycle viz., OH radical, H2O, HCCH, MeSH, MeS radical; VS indicates the product vinyl sulfide. ing step (TS2) and further points were regenerated using MeCCH and MeSH. The regioselectivity of the reaction depends upon the mode of addition of methane thiyl radical (Fig. 5). It has been found that the step involving anti-Markovnikov attack of methane thiyl radical to MeCCH (rate determining step), showed a deduction in the energy barrier by 3.33 kcal/mol in comparison to Markovnikov case (see DE⁄ values; Fig. 5). This expected trend can be attributed to the greater radical stability of the anti-Markovnikov TS. Similar regioselectivity has been reproduced at M06-2X level with an energy barrier difference of 2.51 kcal/mol favoring the antiMarkovnikov product. This value has also been found comparable to the value of 1.61 kcal/mol obtained for familiar bromine radical addition to MeCCH which also favors the same regioselectivity. Thus it could be elucidated that the radical catalyzed pathway proceeds with high degree of regioselectivity leading to the antiMarkovnikov products which is in agreement with the experimental result [19,21]. Stereoselectivity of the final product is decided by the step corresponding to transition structures analogous to TS3 in Fig. 3. This step involves approach of water molecule either in a cis/trans manner leading to the E/Z product respectively and their corresponding transition structures are given in Fig. 6. Comparison of the corresponding energy barriers (Fig. 6) revealed that the formation of Z product is favourable by 0.33 kcal/mol. This small energy difference between the two isomers suggest that our result goes hand in hand with the experimental reports on the unselective mixture of (E/Z) anti-Markovnikov products for the concerned reaction [19,21]. In comparison to gas phase reactions, these radical catalyzed reactions were also found highly feasible due to its relatively small energy barriers. Our present study and its results accomplished a detailed analysis on the mechanistic and energetic aspects of uncatalyzed and radical catalyzed alkyne hydrothiolation reaction. Based on these results and already available transition metal catalysts, studies to unravel sustainable regio- and stereoselective catalysts for this reaction are underway. 4. Conclusions The present work explored the reaction mechanism for alkyne hydrothiolation reactions in gas phase. Two possible addition mechanisms- concerted pathway and multistep reaction pathway were proposed and the present study confirmed the concerted pathway ruling out the latter. Analysis of the reduced natural charges developed on the transition structure and the computed geometrical parameters indicated that the TS could be envisaged 20 E.G. Jayasree, S. Reshma / Computational and Theoretical Chemistry 1098 (2016) 13–21 Fig. 5. Optimized geometries of TS2-both Markovnikov and anti-Markovnikov cases with corresponding energy barrier values. Fig. 6. Optimized geometries of TS3- both E-anti-Markovnikov and Z-anti-Markovnikov cases with corresponding energy barrier values. as a hypothetical ion pair involving thiolate anion and protonated acetylene. It could also be concluded that any factor that stabilize the ion pair would favor the reaction. By comparing the Markovnikov’s and E-anti-Markovnikov’s addition reactions, it has been found that most of the computed systems favor Markovnikov product formation. Small energy difference between the two makes the E-anti-Markovnikov product formation also a feasible reaction. A hydroxyl radical catalyzed multistep pathway has been computationally explored as an attempt to look at the energy barrier in comparison to uncatalyzed reactions. It could be elucidated that the radical catalyzed pathway proceeds with high degree of regioselectivity, while it lacks stereoselectivity, leading to an unselective mixture of (E/Z) anti-Markovnikov product in agreement with experimental results. Acknowledgment This work was supported by the Department of Science and Technology – Science and Engineering Research Board (DST-SERB), New Delhi [grant number SB/FT/CS-078/2013] and the Kerala State Council for Science, Technology and Environment (KSCSTE) [grant number 73/2016/KSCSTE]. Appendix A. 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See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles. methyl-4,5,6,7-tetrahydro-4,7-methano-2-indazolyl]pyridine (9): yield method A, 11%, method C, 60%; mp 132.5-134 °C; NMR ymlI (KBr) 2900,1590,1440,1360,1290, 940, 780 cm-1; (300 MHz) 5h 0.73 (s, 3 H, syn-8"-CHg), 1.00 (a, 3 H, anti-8"-CHJ, 1.24 (m, 1 H, endo-H5"), 1.35 (s, 3 H, 7"-CH3), 1.43 (m, 1 H, endo-H6"), 1.90 (m, 1 H, exo-H6"), 2.13 (m, 1 H, exo-H5"), 2.31 (s, 3 H, S'-CHa), 2.74 (s, 3 H, 5'-CH3), 2.83 (d, 1 , H4"), 6.01 (s, 1 , H4'), 7.62 (dd, 1 H), 7.68 (dd, 1 , H3 and H5) 7.80 (dd, 1 , H4), 7.98 (s, 1 , H3"); 13C NMR Sc 10.6 (7"-CH3), 13.6 O'-CHs), 15.1 (S'-CHg), 19.0 (onít-8"-CH3), 20.7 (syn-8"-CH3), 27.5 (C5"), 33.7 (C6"), 47.1 (C4"), 50.3 (C8"), 60.0 (C7"), 107.8 (C5), 109.2 (C4'), 110.4 (C3), 118.6 (C3"), 129.4 (C3a"), 140.5 (C4), 141.2 (C5'), 149.8 (C3'), 170.0 (C7a"). Anal. Caled for C^H^: C, 72.6; H, 7.3; N, 20.2. Found: C, 72.0; H, 7.3; N, 19.9. 2-Bromo-6-(3,5-diinethyl-lV-pyrazolyl)pyridine (10): yield method A, 52%; mp 75.5-76.5 °C (KBr) 1570,1420,1400, NMR (300 MHz) SH 2.28 (s, 3 H, 1110, 970, 780, 710 cm-1; y-CHg), 2.65 (s, 3 H, S'-CHg), 5.99 (s, 1 , H4'), 7.29 (d, 1 , H3), 7.60 (t, 1 , H4), 7.84 (d, 1 H, H5); 13C NMR 5C 13.6 (3'-CH3), 14.7 (S'-CHa), 109.7 (C4'), 113.5 (C5), 124.2 (C3), 138.8 (C2), 140.2 (C4), 142.2 (C5')> 150.5 (C3')· Anal. Caled for C10H10BrN3: C, 47.6; , 4.0; N, 16.7. Found: C, 47.8; H, 3.8; N, 16.9. Supplementary Material Available: 1H and 13C NMR spectra of all new ligands. Preparations, elemental analyses and IR spectra of the copper complexes of the ligands (15 pages). Ordering information is given on any current masthead page. Three-Center Transition Structures for Alkene Hydroboration and Alkylborane Rearrangement lb MP2/6-31G* 2b MP2Z6-31G· HF/6-31G* and MP2/6-31G* optimized structures for the «--complex of dimethylborane and ethylene and the transition structure for hydroboration. Figure Nicolaas J. R. van Eikema Hommes and Paul von Ragué Schleyer* 1. Instituí für Organische Chemie der Friedrich-Alexander Universit&t Erlangen-Nürnberg, Henkestrasse 42, D-8520 Erlangen, Germany Received December 4,1990 The mechanistic details of alkene hydroboration,1 one of the basic reactions in modern organic chemistry,2 3have intrigued both experimental and theoretical chemists for more than three decades.3-7 Several basic questions remain unanswered, which we will address in this paper using high-level ab initio theory: (1) Is there a «--complex in- 3 termediate in the hydroboration reaction? (2) What is the Figure 2. MP2/6-31G** optimized transition structure for in- (1) Brown, H. C.; Subba Rao, B. C. J. Am. Chem. Soc. 1959,81,6423, 6428. (2) (a) Brown, H. C. Hydroboration; W. A Benjamin: New York, 1962. (b) Brown, H. C. Boranes in Organic Chemistry; Cornell University Press: Ithaca, NY, 1972. (3) For a review, see: Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Comprehensive Organometallic Chemistry; Pergamon Press: Oxford, 1982; Vol. 7, p 153 ff. (4) (a) Dasgupta, S.; Datta, . K.; Datta, R. Tetrahedron Lett. 1978, 1039. (b) Dewar, M. J. S.; McKee, M. L. Inorg. Chem. 1978,17,1075. (c) Sundberg, K. R.; Graham, G. D.; Lipscomb, W. N. J. Am. Chem. Soc. 1979,101,2863. (d) Egger, M.; Keese, R. Helv. Chim. Acta 1987, 70,1843. (5) (a) Clark, T.; Schleyer, P. v. R. J. Or ganóme t. Chem. 1978,156, 191. (b) Nagase, S.; Ray, N. K.; Morokuma, K. J. Am. Chem. Soc. 1980, 102, 4536. (c) Houk, K. N.; Rondan, N. G.; Wu, Y.-D.; Metz, J. T.; Paddon-Row, . N. Tetrahedron 1984, 40, 2257. (d) Koga, N.; Ozawa, T.; Morokuma, K. J. Phys. Org. Chem. 1990, 3, 519. (6) Wang, X.; Li, Y.; Wu, Y.-D.; Paddon-Row, . N.; Rondan, N. G.; Houk, K. N. J. Org. Chem. 1990, 55, 2601. (7) (a) Streitwieser, A., Jr.; Verbit, L; Bitman, R. J. Org. Chem. 1967, 32,1530. (b) Pasto, D. J.; Kang, S.-Z. J. Am. Chem. Soc. 1968,90, 3797. structure of the transition state? Does it have four-center4-6 or three-center7 character? (3) Does the alkylborane rearrangement occur intramolecularly, or does it proceed intermolecularly, by Brown’s2 dissociation/recombination mechanism? We also emphasize the importance of including electron correlation in the geometry optimizations. Prior semiempirical4 56and Hartree Fock ab initio6,6 calculations on model olefin hydroboration reactions indicate the formation of weakly bound -complexes, four-center transition states, and activation barriers between 6 and 12 kcal/mol. However, the barriers decrease when electron correlation is taken into account.6,8 Indeed, for the parent reaction of borane and ethylene, no transition structure 0022-3263/91/1956-4074$02.50/0 tramolecular rearrangement of ethylborane. (8) Wilcox, C. F.; Schleyer, P. v. R., unpublished results, Erlangen, 1988. © 1991 American Chemical Society J. Org. Chem., Vol. 56, No. 12, 1991 Notes H2C=CH„ HBiCHg),, C2H4 + C2H7B -complex TS 2 1 6-31G* 77.60099 103.91885 181.51984 181.52250 181.48431 78.03172 104.49263 182.52435 182.52580 182.49142 0.9 0.0 21.6 1.7 0.0 20.3 1 TS 2 78.29486 104.84309 183.13795 183.14303 183.14017 78.28503 104.82892 183.11395 183.11930 183.11591 3.4 0.0 1.8 C(l) C(2) B H(B) “HBR2" C(l)-C(2) -0.416 -0.416 78.31980 104.87984 183.19964 183.29436 183.19774 -0.426 -0.426 -0.412 -0.415 2.1 TS 3 corr corr -0.394 -0.394 -0.259 0.330 0.059 0.270 (0.322) 0.037 (-0.003) 0.716 0.784 0.669 -0.122 -0.007 -0.091 -0.054 2.028 0.007 0.007 0.000 0.966 1.849 0.047 0.047 0.001 0.933 0.933 2 -0.334 (-0.340) -0.474 (-0.448) -0.097 0.966 3.0 0.0 4.2 -0.248 -0.596 0.779 1.885 MP4SDTQ 2.7 -0.415 -0.425 -0.118 2.034 MP3 0.0 5.4 Table III. NAO Charges and NAO-Wiberg Bond Indexes1 TS -complex 1 corr HF corr HF C(l)-B C(2)-B C(1)-H(B) B-H MP4SDTQ 3.4 0.0 C2H4 + C2H7B HF MP3 78.30597 104.86453 183.17050 183.17480 183.16615 Table II. Relative Energies (kcal/mol) 6-31G* MP2fc MP2fu/6-31G* 3-21G compound C2H4 + C2H7B -complex Table I. Absolute Energies (-au) MP2fc MP2fu/6-3lG* 3-21G compound 4075 0.021 -0.252 1.370 0.357 0.571 0.192 0.709 1.456 0.325 0.403 0.071 0.799 (1.526) (0.287) (0.341) (0.045) (0.840) 1.463 0.377 0.377 0.036 0.876 HF: RHF-NAO charges and bond indexes for RHF-optimized structures. Corr: Correlated (MP4) NBO charges and bond indexes at MP2-optimized structures. Values for 6-31G* augmented with p-type polarization functions on H(B) are given in parentheses. 1 exists at the MP2/6-31G* level.® The experimental data Fehlner9 reported a free energy of activation of 2 ± 3 kcal/mol for this reaction in the gas phase, but this has been attributed to the entropy contribution.® Higher barriers are expected with alkylboranes, due to substituent stabilization and steric effects. Hence, we have now examined the reaction of dimethylborane and ethylene at correlated levels and have optimized the -complex and the transition structure at MP2/6-31G*.10 Furthermore, we investigated a structural alternative for the -complex of ethylene and borane, which might be involved in alkylborane rearrangements. The HF/6-31G* and MP2/6-31G* structures for the dimethylborane-ethylene -complex 1 and the transition structure 2 are compared in Figure 1. Absolute and relative energies are given in Tables I and II, respectively. The HF/6-31G* complexation energy for dimethylborane with ethylene is only -0.9 kcal/mol, but this increases with are sparse. correlation to -3.0 kcal/mol (MP4SDTQ/6-31G*// MP2/6-31G*). As a consequence of the greater binding energy at correlated levels, the borane becomes considerably more pyramidal and the distance to the C-C double bond decreases by more than 0.8 A (see Figure 1). Changes due to correlation also are apparent from the NBO charges1" and Wiberg bond indexes10* listed in Table III. -Donation from ethylene into the empty boron p orbital (9) Fehlner, T. J. Am. Chem. Soc. 1971, 93, 6366. (10) (a) GAUSSIAN « Frisch, M. J.; Head-Gordon, M.; Schlegel, . B.; Raghavachari, K.; Binkley, J. S.; Gonzalez, C.; DeFrees, D. J.; Fox, D. J.; Whiteside, R. A; Seeger, R.; Melius, C. F.; Baker, J.; Kahn, L. R.; Stewart, J. J. P.; Fluder, E. M.; Topiol, S.; Pople, J. A, Gaussian, Inc., Pittsburgh, PA. (b) Cadpac: Amos, R. D.; Rice, J. E. The Cambridge Analytical Derivatives Packages, Issue 4.0; Cambridge, 1989. (c) 3-21G basis set: Binkley, J. S.; Pople, J. A; Hehre, W. J. J. Am. Chem. Soc. 1980,102, 939. (d) 6-31G* basis set: Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta 1973,28, 213. Francl, . M.; Pietro, W. J.; Hehre, W. J.; Binkley, J. S.; Gordon, M. S.; DeFrees, D. J.; Pople, J. A. J. Chem. Phys. 1982, 77, 3664. (e) Meller-Plesset theory: Pople, J. A.; Binkley, J. S.; Seeger, R. Int. J. Quantum Chem., Symp. 1976,10,1 and references cited therein, (f) Natural bond orbital analysis method: Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988,88,899 and references cited therein, (g) Wiberg bond index: Wiberg, K. Tetrahedron 1968, 24, 1083. Figure 3. HF/6-31G** optimized structures for the -complex of ethylene and borane. amounts to 0.054 e in the MP2-optimized complex; a C-B bond index of about 0.05 results. In contrast, these interactions in the RHF complex are almost neglegible. Electron correlation changes the interpretation of the nature of the transition structure (TS). At HF/6-31G*, the TS 2a (which resembles that described by Houk et al.®) appears to involve four centers: H(B) is only 1.7 A away from C(l), and the two C-B distances differ by 0.12 A in length. In contrast, the MP2-optimized TS 2b has three-center character! The H(B) is farther away from C(l), and the two C-B distances are nearly the same. This conclusion is supported by the bond orders in Table III. Use of p-type polarization functions on the migrating hydrogen increases the C(1)-H(B) distance even further and leads to even weaker bonding (Figure 1, Table III, values in parentheses). At MP2, the transition structure comes earlier along the addition path than that located at the RHF level. At MP4SDTQ/6-31G*, the overall activation barrier from the separated reactants is 1.2 kcal/mol, and 4.2 kcal/mol from the complex. These differences between RHF- and MP2-optimized transition structures for the hydroboration reaction may have some important consequences: RHF-optimized structures have been used for the analysis of endo vs exo J. Org. Chem. 1991, 56, 4076-4078 4076 Scheme I additions to norbornene50 and for the development of molecular mechanics force fields for the study of regioselectivity.5” It would be desirable to ascertain if the MP2 geometries give significantly different results. We also investigated a new structure 3 for the complex of borane and ethylene, in which the unique B-H is perpendicular rather than parallel to the C-C double bond (Figure 2). Indeed, 3 is the only minimum for the complex at the RHF level (the B-H parallel form, studied by earlier investigators,5,6 is a transition structure at RHF; see Figure 3). However, 3 is a transition structure when optimized at MP2. The imaginary vibration corresponds to rotation of the BH3 unit; the reaction path then leads directly to ethylborane.6 Hence, complex 3 represents the transition structure for degenerate rearrangement of ethylborane, H2BCH2CH3 í 3 p! CH3CH2BH2. The three-center bonding in transition structure 3 is characterized by a substantial ir-donation, 0.252 e, from ethylene to boron and by C-B and C-C bond indexes comparable to those found in the transition structure for addition, 2b (Table III). Such intramolecular boron migrations occur stereospecifically, as was found experimentally, e.g., with cyclic substrates under mild reaction conditions.11 At higher temperatures, mixtures are obtained, as expected from Brown’s alternative dehydroboration/hydroboration mechanism.2 Our results agree nicely. We calculate the migration barrier (AEJ in ethylborane to be 23 kcal/mol RC02H RCONR1R2 2 1 UODU j_> 1 3 [swp®-s®] r [ Ph3Sb(OCOR)2 ] RCOSH -- · 4 4 + 2 PhjSbO 3 Table I. Ph,SbO/P4S10-Catalyzed Amidation of Carboxylic Acids” amides AcNH-n-Hex4 method” T(°C) t (h) yields6 (%) A 40 80 80 80 40 60 60 50 40 60 50 80 80 80 80 80 30 30 30 30 30 5 90 0 0 0 80 75 69 A' Af A‘ AcNH-t-Bu AcNEti AcNHPh AcNHCH2CH2OH AcNHCH2CH=CH2 Cl2CHCONHPr CHz—CHCONH-t-Pr t-BuCONH-t-Bu t-BuCONHPh (MP4SDTQ/6-3lG**//MP2/6-3lG**), whereas dissocia- (CH2CH2CO)2(NHPr)2 tion into ethylene and borane requires 31.5 kcal/mol. The latter process, however, is favored by entropy. For this model reaction, we calculate the free energies of activation to be nearly equal at 300 K, 22.5 kcal/mol. The dissociation mechanism prevails at higher temperatures, while intramolecular rearrangement is favored below this temperature. Note Added in Proof. After this note was submitted, we located the TS for reaction of borane and ethylene at the RQCISD/6-31G** level, which also exhibits threecenter character. The activation barrier, relative to the -complex, is 0.05 kcal/mol at RQCISD(T)/6-311+G**/ /RQCISD/6-31G**. BzNH-t-Bu BzNHPh Z-Gly-Gly-OEt Z-Phe-Leu-OEt Z-Leu-Phe-OMe Z-Ser-Gly-OEt Z-Tyr-Gly-OEt A A A B B A1' A B A A A A C C C C C 12 12 24 6 12 5 1 0.5 8 6 12 5 6 24 5 0.5 2 2 2 2 956 906 96 56 886 87 65 65 75 83 75 73 71 79 "Reaction conditions: l/2/Ph3SbO/P4Si0 = 5/5/0.25/0.75; 20 mL of solvent. 6 Isolated yield. c Details of methods A, B, and C are given in the Experimental Section. dn-Hex denotes n-CeHl3. "No P4S10 was present. fNo Ph3SbO was present. 1 Neither 6 Ph3SbO nor P4S10 was present. Yield based on 1. ’CHC13 was the solvent. popularity is markedly lower than that of acyl chlorides, anhydrides, and such active esters as thiol esters.3 This has much to do with their limited availability,4 higher susceptibility to autoxidation,5 and unpleasant odor. In our continuing studies on the utilization of organoantimony compounds in organic synthesis, triphenylstibine oxide (Ph3SbO) was found to catalyze several condensation reactions,6 including the aminolysis of thiocarboxylic acids by amines to give amides.2 It was also found that, in the presence of tetraphosphorus decasulfide (P4S10), Ph3SbO accelerated the thiolation of carboxylic acids to the corresponding thiocarboxylic acids 4.7 Thus, we deduced that Acknowledgment. This work was supported by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and Convex Computer Corporation. N.J.R.v.E.H. thanks the Alexander von Humboldt foundation for a research fellowship. (11) (a) Wood, S. E.; Rickbom, B. J. Org. Chem. 1983, 48, 555. (b) Field, L. D.; Gallagher, S. P. Tetrahedron Lett. 1985, 26, 6125. Facile One-Pot Amidation of Carboxylic Acids by Amines Catalyzed by Triphenylstibine Oxide/Tetraphosphorus Decasulfide (2) Nomura, R.; Wada, T.; Yamada, Y.; Matsuda, H. Chem. Express 1988, 3, 543. (3) Sandler, S. R.; Karo, W. Organic Functional Group Preparations, 2nd ed.; Academic Prese: San Diego; 1983; Chapter 11. Jones, J. H. In The Peptides; Gross, E., Meienhofer, J., Eds.; Academic Press: New York, 1979; Vol. 1, Chapter 2. (4) So far, methods for the preparation of thiolcarboxylic acids have been largely limited to the classical hydrogen sulfide-promoted thiolation and hydrolysis of thiocarboxamides. See: Schóberl, A.; Wagner, A. In Methoden der organischen Chemie, 4th ed.; Müller, E., Ed.; Thieme: Stuttgart, 1955; Vol. 9, Chapter 23. (5) Janssen, M. J. In The Chemistry of Carboxylic Acids and Esters; Patai, S., Ed.; Interscience: New York, 1969; p 723. (6) (a) Nomura, R.; Yamada, Y.; Matsuda, H. Appl. Organomet. Chem. 1988, 2, 557. (b) Nomura, R.; Yamamoto, M.; Matsuda, H. Ind. Eng. Chem. Res. 1987,26,1056. (c) Nomura, R.; Wada, T.; Yamada, Y.; Matsuda, H. Chem. Lett. 1986,1961. (d) Matsuda, H.; Baba, A.; Nomura, R.; Kori, M.; Ogawa, S. Ind. Eng. Chem. Prod. Res. Dev. 1985, 24, 239. (e) Nomura, R.; Kori, M.; Matsuda, H. Chem. Lett. 1985, 579. (Ph,SbO/P4S10) Ryoki Nomura,* Takahiro Nakano, Yasuhiro Yamada, and Haruo Matsuda Department of Applied Chemistry, Faculty of Engineering, Osaka University, Yamada-Oka, Suita, Osaka 565 Japan Received November 1, 1990 Although thiocarboxylic acids are useful acylating reagents for the synthesis of amides and peptides,1,2 their (1) Yamashiro, D.; Blake, J. Int. J. Pept. Prot. Res. 1981, 18, 383. Blake, J.; Yamashiro, D.; Ramsharma, K.; Li, C.-H. Ibid. 1986,28, 468. 0022-3263/91/1956-4076$02.50/0 Ph3SbO/P4S10 +r1r2nh © 1991 American Chemical Society