Transition-Metal-Free C-Vinylation of Ketones with Acetylenes: A

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Transition metal-free C-vinylation of ketones with acetylenes: a quantum-chemical rationalization of similarities and differences in catalysis by superbases MOH/DMSO and tBuOM/DMSO, M = Na, K. Vladimir B. Orel, Nadezhda M. Vitkovskaya, Vladimir B. Kobychev, and Boris A. Trofimov J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00071 • Publication Date (Web): 05 Mar 2018 Downloaded from http://pubs.acs.org on March 5, 2018

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The Journal of Organic Chemistry

Transition metal-free C-vinylation of ketones with acetylenes: a quantumchemical rationalization of similarities and differences in catalysis by superbases MOH/DMSO and tBuOM/DMSO, M = Na, K. Vladimir B. Orel,†, ‡ Nadezhda M. Vitkovskaya,† Vladimir B. Kobychev,† and Boris A. Trofimov‡ ∗ †

Laboratory of Quantum Chemistry, Irkutsk State University, 1 K. Marks St., 664003 Irkutsk, Russian Federation

‡

A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky St., 664033 Irkutsk, Russian Federation

ABSTRACT Transition metal-free C-vinylation of acetone with phenylacetylene catalyzed by superbases MOH/DMSO and tBuOM/DMSO (M = Na, K) has been theoretically evaluated in B3LYP/6311++G**//B3LYP/6-31+G* approach to rationalize similarities and differences in activity of the above catalytic systems. The close solvate surroundings of sodium and potassium tert-butoxides has been studied. Formation of tBuOM·nDMSO complexes, their structure and thermodynamic stability is discussed in comparison with similar complexes of alkali metal hydroxides MOH·nDMSO. Activation barriers of the title reaction in the presence of tBuOM·nDMSO complexes are found to be less than those with the MOH·nDMSO complexes participation. 1. INTRODUCTION In the last decade, application of the superbasic reagents and catalysts has paved the route to conceptionally new acetylene-based syntheses of fundamental organic compounds.1–6 Recently discovered C-vinylation of ketones with acetylenes7 catalyzed by superbase systems of the MOH/DMSO or tBuOM/DMSO (M = Na, K) now serves as a springboard to trigger transition metal-free one-pot cascade assemblies of such fundamental organic compounds as functionalized cyclopentenes,2 furans,4,8 oxazoles,1 pyrazoles,9,10 benzoxepine,11 pyrimidines,12 analogs of natural pheromones.1 A number of syntheses based on this reaction is rapidly extending, but there are still ∗

Corresponding author. Boris A. Trofimov Tel.: +7-3952-422-423; fax: +7-3952-419-346; e-mail: [email protected] 1 ACS Paragon Plus Environment

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topical issues related to the mechanistic features of these processes as well as to the special role of the above superbases. Among diverse superbases, the KOH/DMSO pair proved to be the most suitable for the systematic application in the acetylene chemistry as the simplest, most easily prepared and versatile system. A characteristic feature of this system is its autostabilization (self-tuning): its basicity is maintained at one level due to the absorption of water (if it is formed in the reaction) by the solid phase (KOH); the concentration of KOH in the liquid phase is small (~ 0.04 M for pure DMSO) and is replenished in the case of consumption from the solid phase, i.e. is automatically maintained constant, which promotes a gentle flow of chemical processes. In the syntheses of methylene-6,8dioxabicyclo[3.2.1]octanes from 1,5-diketones,13 aliphatic and alicyclic ketones14 and acetylene, the KOH/DMSO system is even more effective than the superbasic media based on potassium tertbutoxide. As to the tBuOM/DMSO pair, they are strong enough to deprotonate some hydrocarbons and weak CH-acids.15 Although similar acidity of water (pKa = 31.416) and tert-butanol (pKa = 32.216) in dimethyl sulfoxide, the potassium tert-butoxide is readily soluble in DMSO,17 which ensures homogeneity of the reaction mixture and a high concentration of base in it. This superbase is widely used to effect β-elimination reactions and isomerizations of unsaturated systems.18 In the reactions of vinylation of ketones7 and carbohydrates,1 annulation of fluorophenylacetylenes with ketones,11 syntheses of 4,5-dihydropyrazoles,9 acylterphenyls19 and furans,8 alkali metal tert-butoxide-tailored systems prove to be more effective than those based on hydroxides. For example, promoting activity of the MOR/DMSO systems in the α-vinylation of acetone with phenylacetylene increases threefold when superbase changes from KOH/DMSO to tBuOK/DMSO.7 Analogously, the αvinylation of cyclohexanone with phenylacetylene in presence of potassium tert-butoxide provides up to 90% yield of (E)-2-styrylcyclohexanone for 30 minutes, whereas in the presence of KOH, even only twice as long, only 60% yield is achieved.7 Quantum chemical modeling of transition metal-free C-vinylation of ketones with acetylenes should help understanding the mechanism of these reactions as well as identifying similarities and differences between MOH/DMSO and tBuOM/DMSO systems. Our recent studies on the structure of solvated complexes of potassium and sodium hydroxides have shown that the closest solvate surrounding of non-dissociated molecules of NaOH and KOH consists of four and five molecules of a dimethyl sulfoxide, respectively.20 The simulation of nucleophilic addition of acetone to phenylacetylene (C-vinylation of acetone) in the presence of KOH·5DMSO indicated that elementary acts of the studied reaction occured on the periphery of the superbasic complex.21 Thus, differences in activity of alkali metal hydroxides and tert-butoxides could be caused by the structural peculiarities of the formed solvated-loosened pairs 2 ACS Paragon Plus Environment

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of the type K+(Na+)/(Me2SO)n/OH(OtBu) and by the degree of such a loosening, which characterizes activity of the anion.20,21 Another important reason is the difference in a structure of the reaction center (transition state) in the course of the reaction. So, the water molecule, formed in the MOH/DMSO systems in the reactions of nucleophilic addition to acetylene, decreases catalytic activity of the superbases.20 The systematic structural studies of the superbase reactive centers and sequences of their transformations during the reactions with their participation would gain a clearer insight into the mechanisms of superbase catalysis. The present work reports a quantum-chemical study of the nearest solvate surrounding of hydroxides and tert-butoxides of sodium and potassium, formation of tBuOM·nDMSO complexes, their structure and thermodynamic stability is discussed in comparison with similar complexes of alkali metal hydroxides MOH·nDMSO. Using C-vinylation of acetone with phenylacetylene as a model reaction (Scheme 1), catalytic activity of the superbasic systems tBuOM/DMSO and MOH/DMSO is compared.

Scheme 1. Addition of acetone to phenylacetylene.7 A role of the tBuO–, HO– anions and the alkali metal cations at the stage of acetone molecule deprotonation is evaluated. The effect of the formed tert-butyl alcohol in comparison with water molecule on the nucleophilic addition of enolate-ion to phenylacetylene is determined. Activation barriers of the reaction in question with tBuOM·nDMSO complexes explicitly included are calculated.

2. COMPUTATIONAL DETAILS Structural parameters of the systems under study were optimized by density functional theory (DFT) at the B3LYP22,23 level of theory using the 6-31+G* basis set. The vibrational corrections to enthalpies and entropies were calculated at the same level of theory (B3LYP/6-31+G*) for a standard temperature 298.15 K. For stationary points of PES the number of negative eigenvalues of the Hessian matrix was calculated;

the

connection

of

the

transition

states

found

with

the

corresponding PES minima was proved by the reaction coordinate (IRC) following using the local quadratic approximation algorithm (LQA).24 Further, the energies at the stationary points were refined by using the extended basis set B3LYP/6-311++G**. The energies of some stationary points on the vinylation reaction pathway were also refined using the MP2/6-311++G** approach. Solvation energy in DMSO was computed by the polarizable dielectric model using the IEFPCM model.25 3 ACS Paragon Plus Environment


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To estimate activation free energy in the solution we have used approach, which based upon results by Wertz,26 suggested in article27. Being applied to dimethyl sulfoxide solutions28 this approach suggests that the entropy in DMSO solution Ssol can be obtain from Sharm, the entropy found in the harmonic approximation for ideal gas, as Ssol = 0.74Sharm – 3.21cal·mol–1·K–1

(1)

(see Supplementary for details). All calculations were carried out using the GAUSSIAN-09 program package.29 For complexes of superbases, we searched for the global minimum using the Coalescence Kick (CK) program.30 The CK method subjects large populations of randomly generated structures to a coalescence procedure, in which all atoms are pushed gradually to the molecular center of mass to avoid generation of fragmented structures and then optimized to the nearest local minima. Then preliminary optimization of the generated structures was performed using semiempirical approach realized in Laykov’s PRIRODA program.31 The isomers with relative energies < 25 kcal/mol were further recalculated at B3LYP/6-311++G**//B3LYP/6-31+G* level of theory.

3. RESULTS AND DISCUSSION The first coordination shell of tBuONa and tBuOK in a dimethyl sulfoxide solution. The developed models of the superbasic systems MOH/DMSO (M = Na, K)20 are based on their known physical-chemical properties, namely weak dissociation of alkali metals hydroxides (Table 1)32 and a specific solvation of the corresponding cations33 in dimethyl sulfoxide. Calculation of the dissociation energies of NaOH and KOH in dimethyl sulfoxide, which accounts only for nonspecific solvation at the level of PCM continuation model, predicts an incorrect ratio ∆GNaOH < ∆GKOH (Table 1, PCM (M+)). When the only molecule of dimethyl sulfoxide is included in the calculations for the reactions MOH·DMSO → M+·DMSO + OH–, a good agreement with the experimental results is reached (Table 1, PCM (DMSO·M+)). The experimental data on the degree of dissociation of alkali metals tert-butoxides in DMSO are lacking in the literature. Our calculation predicts that the molecules of potassium and sodium tert-butoxides like their hydroxides very limitedly dissociate in DMSO (Table 1). We have studied the structure of tBuONa and tBuOK complexes with molecules of nearest solvate surrounding by analogy with NaOH·4DMSO and KOH·5DMSO complexes investigated earlier. Table 1. Free dissociation energies in kcal·mol-1 of potassium and sodium hydroxides and tertbutoxides (MOR) in DMSO calculated both using the continuum model only (I) and with an additional molecule of dimethyl sulfoxide (II) compared to experimental values. 4 ACS Paragon Plus Environment

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MOR

I

II

Exp.32

NaOH

7.2

4.3

6.4

KOH

7.4

2.2

4.2

tBuONa

7.6

3.8

–

tBuOK

7.9

1.4

–

On the potential energy surfaces (PES) of tetrasolvate complexes of sodium hydroxide NaOH·4DMSO 120 and sodium tert-butoxide tBuONa·4DMSO 2, global minima correspond to the structures of distorted trigonal bipyramid (Fig. 1). Noteworthy, decrease in the system enthalpy, observed during the formation of complex 2 from tBuONa and four molecules of DMSO, is 11.7 kcal/mol that is only by 2.2 kcal/mol less than the decrease of the system enthalpy for the formation of complex 1 from NaOH and four molecules of DMSO (Table 2).

Figure 1. Structure of global minima of complexes NaOH·4DMSO 1, tBuONa·4DMSO 2, and local minima of complexes КOH·5DMSO 3, tBuOK·5DMSO 4 (bond lengths are given in Å)

Table 2. Enthalpies ∆H of MOR·nDMSO complexes formation from the isolated molecules of MOR bases and n molecules DMSOa, energies ∆E of interaction of MOR bases with a solvate shell of nDMSO (this energies have been calculated at geometry of MOR·nDMSO complex)b and energies ∆EDMSO–DMSO of interaction of DMSO molecules with each other in the complexes MOR·nDMSOc, in kcal/mol.

a

MOR

∆H

∆E

∆EDMSO–DMSO

NaOH

–13.9

–22.6

5.2

NaOtBu

–11.7

–20.3

4.4

KOH

–9.9

–18.3

1.2

KOtBu

–7.7

–17.3

0.9

∆H = H(MOR·nDMSO) – nH(DMSO) – H(MOR), (M = Na+, n = 4; M = K+, n = 5) b ∆E = E(MOR·nDMSO) – E(nDMSO) – E(MORcomp.) c

∆EDMSO–DMSO = E(nDMSO) – nE(DMSO)

5 ACS Paragon Plus Environment


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In the complex NaOH·4DMSO 1, a hydroxide ion forms four hydrogen bonds with four methyl groups of two DMSO molecules (Fig. 1). In the complex tBuONa·4DMSO 2, the tert-butyl moiety spatially hinders the interaction of the tBuO– anion oxygen atom with dimethyl sulfoxide molecules to form only two hydrogen bonds of a tert-butoxide ion with two methyl groups of DMSO molecule DMSO (Fig. 1). These differences in formation of the hydrogen bonds in complexes 1 and 2 slightly influence the energy of interactions between NaOR bases with a solvate shell 4DMSO of these complexes (∆E, Table 2). Besides, in both complexes 1 and 2, the Na–O bond lengths, 2.220 Å and 2.214 Å, respectively, become significantly increased with respect to those in isolated NaOH (1.926 Å) and NaOtBu (1.964 Å) (Fig. 1). These loosening of the bonds are caused by specific interactions with DMSO molecules. When only nonspecific interactions with the solvent are taken into account, i.e. optimization of the base molecule geometry using the PCM model, these bond lengths increase to a lesser extent to R(Na-OH) = 2.137 Å and R(Na-OtBu) = 2.112 Å. In both complexes, DMSO molecules equally strongly repulse from each other (∆EDMSO–DMSO, Table 2). The pentasolvate complex of potassium hydroxide KOH·5DMSO 3 has pseudo-octahedral structure (Fig. 1),20 characteristic for coordination number 6 of a potassium cation. The complex tBuOK·5DMSO 4 has a similar structure (Fig. 1). Decrease in the system enthalpy in complexes 3 and 4 formed from free molecules of a base and five molecules of DMSO as well as in complexes with sodium cation differs slightly. This value is only by 1.3 kcal/mol higher for the complex KOH·5DMSO 3 (Table 2). In the complexes KOH·5DMSO 3 и tBuOK·5DMSO 4, unlike the complexes with sodium cation 1 and 2, DMSO molecules weakly repulse from each other (∆EDMSO–DMSO, Table 2) and energies of KOR base interaction with a solvate shell of 5DMSO differ only by 1 kcal/mol (∆E, Table 2). Specific interactions of KOH and tBuOK with DMSO molecules leads to significant loosening of the K–O bonds with respect to the isolated molecules: ∆R(К-OtBu) = 0.394Å in 4 and ∆R(К−OH) = 0.390Å in 3. Nonspecific interactions result in considerably smaller changes, the

increase in the bond length upon optimization of geometry using the PCM model being only ∆R(К−OH) = 0.214 Å and ∆R(К-OtBu) = 0.194 Å with respect to the isolated molecules KOH and

tBuOK. Thus, the complexes formed by sodium and potassium tert-butoxides with the solvent molecule of first solvate shell are qualitatively and quantitatively similar to the corresponding complexes of their hydroxides. Vinylation of acetone with phenylacetylene: effect of the base nature. Stage of nucleophile initial complex formation. Interaction of the superbase complexes 1 – 4 with an 6 ACS Paragon Plus Environment

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acetone molecule represents an initial stage of the vinylation reaction of acetone with phenylacetylene. The superbasic complexes deprotonate acetone molecule to generate Cnucleophile, enolate-ion. For O-, S- and acetylenic C-nucleophiles (for example, phenylacetylene), deprotonation occurs without activation barriers.20,21,34 Significantly lower mobility of the proton bonded with sp3-hybridized α-carbon atom of ketone causes appearance of the activation barrier (∆G‡ = 9.4 kcal/mol, MP2/6-311++G**//B3LYP/6-31+G*) in the course of stable enolate-ion formation.20 The superbasic complexes NaOH·4DMSO 1 and tBuONa·4DMSO 2 deprotonate an acetone molecule with activation barriers ∆G‡ = 13.1 kcal/mol and ∆G‡ = 13.7 kcal/mol, respectively (Fig. 2) to afford the complexes of sodium enolate, Na+[CH2(CO)CH3]–·H2O·4DMSO 5 (∆H = –6.7 kcal/mol) and Na+[CH2(CO)CH3]–·HOtBu·4DMSO 6 (∆H = –6.0 kcal/mol) (Fig.3).

Figure 2. The reaction profiles of formation of sodium (5 and 6) and potassium (7 and 8) enolate complexes, relative free energies ∆G and enthalpies ∆H (in brackets) of stationary points in kcal/mol.



Figure

3.

Structure

of

the

Na+[CH2(CO)CH3]–·H2O·4DMSO

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5,

Na+[CH2(CO)CH3]–

·HOtBu·4DMSO 6, K+[CH2(CO)CH3]–·H2O·5DMSO 7 and K+[CH2(CO)CH3]–·HOtBu·5DMSO 8. Similar to the systems with a sodium cation, deprotonation of acetone under the action of complexes KOH·5DMSO 3 and tBuOK·5DMSO 4 leads to formation of stable complexes of potassium enolate (Fig. 3), K+[CH2(CO)CH3]–·H2O·5DMSO 7 (∆H = –9.6 kcal/mol) and K+[CH2(CO)CH3]–·HOtBu·5DMSO 8 (∆H = –7.2 kcal/mol). The proton transfer to hydroxide ion in the complex KOH·5DMSO 3, like in the system with sodium hydroxide, is associated with a slightly lower activation barrier (∆∆H‡ = 0.3 kcal/mol and ∆∆G‡ = 1.3 kcal/mol) than the proton transfer to tert-butoxide ion in the complex tBuOK·5DMSO 4 (Fig. 2). The smallest activation barrier ∆G‡ = 11.1 kcal/mol is obtained in the presence of potassium hydroxide complex KOH·5DMSO 3. Further, the barriers increase in the series KOH·5DMSO 3 < tBuOK·5DMSO 4 < NaOH·4DMSO 1 < tBuONa·4DMSO 2 and do not exceed ∆G‡ = 13.7 kcal/mol. At the stage of nucleophile formation, activity of the superbasic systems tBuOM/DMSO turns out to be even slightly lower than that of the system MOH/DMSO. Nucleophilic addition of enolate-ion complexes to phenylacetylene. The reactions of vinylation with phenylacetylene proceeds via a transition state with trans-distortion of the acetylenic fragment to generate carbanions of E-configuration.21 Nucleophilic addition of the sodium enolate

complexes,

Na+[CH2(CO)CH3]–·H2O·4DMSO 5 and Na+[CH2(CO)CH3]–

·HOtBu·4DMSO 6, to a molecule of phenylacetylene furnishes sodium E-4-oxo-5-phenylpentenide complexes, Na+[PhC=CH-CH2(CO)CH3]–·H2O·4DMSO 9 and Na+[PhC=CH-CH2(CO)CH3]– ·HOtBu·4DMSO 10 (Table 3). Carbanion [PhC=CH–CH2(CO)CH3]– in complexes 9 and 10 can be coordinated at sodium cation either by the carbonyl oxygen atom C=O···Na+ or by the carbanionic 8 ACS Paragon Plus Environment

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site CH=PhC–···Na+. In the first case the H2O (or HOtBu) molecule is located at the O–Na+ distance 3.6–4.1 Å comparable to the spacing of DMSO methyl groups. Therefore, this types of location can be characterized as a position in the first solvate shell, and we shall notice complexes with such an inner position of water or tert-butyl alcohol as inner-. In the second case the molecule of H2O (or HOtBu) leaves the nearest solvation shell to locate at a distance 5.9–6.1 Å, being denoted as outer-. The formation of inner-9 complex relates to increase in the system enthalpy by 12.7 kcal/mol and occurs with an activation barrier ∆H‡ = 18.0 kcal/mol, ∆G‡ = 25.2 kcal/mol through the transition state inner-TS5→9, in which the molecule of phenylacetylene is remote from sodium cation, and the hydrated enolate ion retains the initial coordination relative to cation by the carbonyl oxygen atom (Table 3).



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Table 3. Enthalpies ∆H‡, free activation energies ∆G‡ and thermal effects ∆H of the formation of sodium E-4-oxo-5-phenylpentenide carbanion complexes 9–12 in kcal/mol and the related transition states. Transition states

inner-TS5→9

outer-TS5→9

inner-TS6→10

outer-TS6→10

TS7→11

a

TS8→12

Carbanion complexes

∆H‡

∆G‡

∆H

18.0

25.2

12.7

19.8

26.7

6.8

16.7

24.3

6.9

16.6

22.5

2.9

17.8 (11.7)a

24.6 (18.5)

7.0

15.5 (9.9)

21.3 (15.8)

4.6

inner-9

outer-9

inner-10

outer-10

11

12

The activation barriers in the MP2/6-311++G**//B3LYP/6-31+G* approach are given in brackets.


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The formation of outer-9 complex proceeds through the transition state outer-TS5→9 and is accompanied by a lower by 5.9 kcal/mol increase of the enthalpy, but a higher (by ∆∆H‡ = 1.2 kcal/mol, ∆∆G‡ =1.5 kcal/mol) activation barrier, than with the formation of the complex inner-9 (Table 3). In the transition state outer-TS5→9, the triple bond of phenylacetylene molecule is oriented toward the sodium cation, while enolate ion and water molecule, coordinate with this ion, are remote from the cationic center. In the system with tert-butyl alcohol, outer-complex Na+[PhC=CH-CH2(CO)CH3]– ·HOtBu·4DMSO 10 is also thermodynamically more favorable (by ∆∆H = 4.0 kcal/mol). However, its formation via the transition state outer-TS6→10 is associated with a lower by ∆∆H‡ = kcal/mol 1.3 kcal/mol and ∆∆G‡ = 1.8 kcal/mol activation barrier than formation of inner-10 complex through the transition state inner-TS6→10 (Table 3). It should be noted that in the transition states TS6→10, the enolate ion is coupled with a molecule of tert-butyl alcohol, which is located either in the surroundings of the cation inner-, or out of it (outer-) (Table 3). Localization of tert-butyl alcohol in the second solvate shell, for example, in the complexes of sodium or potassium enolates, Na+[CH2(CO)CH3]–·HOtBu·4DMSO 6 and K+[CH2(CO)CH3]– ·HOtBu·5DMSO 8, with formation of the corresponding outer-complexes (Fig. 4) proceeds without significant barriers, enthalpy of the system being increased by no more than 0.5 kcal/mol. Therefore such rearrangement of HOtBu molecule almost does not effect on energy values of the transition state. Also, in the system with tert-butyl alcohol, a lower activation barrier is associated with formation of thermodynamically more stable carbanioin complex outer-10 that agrees with Hammond postulate.

Figure 4. Structure of sodium and potassium enolate complexes Na+[CH2(CO)CH3]– ·HOtBu·4DMSO 6 K+[CH2(CO)CH3]–·HOtBu·5DMSO 8 with localization of tert-butyl alcohol in the second solvate layer At the same time, for the system with a water molecule, a higher energy of the transition state outer-TS5→9 in comparison with energy of the transition state inner-TS5→9 is due to considerable energy consumption for transition of a water molecule in complexes of the superbases 11 ACS Paragon Plus Environment


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to the next solvate layer (~ 4.5 kcal/mol for NaOH·4DMSO·H2O and ~ 3 kcal/mol for KOH·5DMSO·H2O).20 In general, nucleophilic addition of sodium enolate complex, Na+[CH2(CO)CH3]– ·HOtBu·4DMSO 6, containing a molecule of tert-butyl alcohol, to phenylacetylene occurs with a lower (by ∆∆H‡ = 2.0 kcal/mol, ∆∆G‡ = 2.7 kcal/mol) activation barrier than nucleophilic addition of sodium enolate complex Na+[CH2(CO)CH3]–·H2O·4DMSO 5 containing a water molecule (Table 3, Fig. 5).

Figure 5. Reaction profiles of nucleophilic addition of sodium (5 and 6) and potassium (7 and 8) enolate complexes to a molecule of phenylacetylene, relative free energies ∆G and enthalpies of ∆H (in brackets) of stationary points in kcal/mol. Vinylation of potassium enolate complex, K+[CH2(CO)CH3]–·HOtBu·5DMSO 8, containing also tert-butyl alcohol, by a molecule of phenylacetylene is related to even lower (by 1.2 kcal/mol) activation barrier (Table 3, Fig. 5) than vinylation of sodium enolate complex, Na+[CH2(CO)CH3]– 12 ACS Paragon Plus Environment

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·HOtBu·4DMSO 6. At the same time, the activation barrier of vinylation of the potassium enolate hydrated complex, K+[CH2(CO)CH3]–·H2O·5DMSO 7, is higher (by ∆∆H‡ = 3.4 kcal/mol, ∆∆G‡ = 3.3 kcal/mol) than a barrier of complex 8 vinylation (Table 3, Fig. 5). Formation of potassium E-4oxo-5-phenylpentenide complexes K+[PhC=CH-CH2(CO)CH3]–·H2O·5DMSO 11 and K+[PhC=CHCH2(CO)CH3]–·HOtBu·5DMSO 12 is accompanied by increase in the system enthalpy by 7.0 and 4.0 kcal/mol, respectively (Fig. 5). Note that the activation barriers of nucleophilic addition of 7 and 8 to phenylacetylene obtained using the MP2/6-311++G**//B3LYP/6-31+G* approach (given in brackets in Table 3) become slightly smaller than those found by the B3LYP/6311++G**//B3LYP/6-31+G* method. Nevertheless, both MP2 and DFT approaches predict similar lowering of the activation energy when changing the water complex 7 with the tert-buthyl alcohol complex 8. Activation barriers of potassium and sodium enolate complexes nucleophilic addition to a molecule of phenylacetylene, which is a rate-determining stage in the formation of β,γ-unsaturated ketones, in the systems with tert-butyl alcohol are lower than those in the systems containing a water molecule. The values of activation barrier for vinylation of enolate ions with phenylacetylene decrease in the series Na+[CH2(CO)CH3]–·H2O·4DMSO 5 > K+[CH2(CO)CH3]–·H2O·5DMSO 7 > Na+[CH2(CO)CH3]–·HOtBu·4DMSO 6 > K+[CH2(CO)CH3]–·HOtBu·5DMSO 8 (Fig. 5). These results are in good agreement with experimentally observed increase in yields of products of acetone vinylation in the series of superbasic systems NaOH/DMSO (10%) < KOH/DMSO (20%) < KOtBu/DMSO (70%).7 It is known that the presence of water hinders the vinylation reactions in superbasic media.35,36 Our quantum-chemical calculations20 show that water molecules can hydrate the initial nucleophile, reducing its activity, and the activation barrier of the reaction being increased owing a larger stabilization of the starting reagents relative to the corresponding transition state. The activation barrier of nucleophilic addition of "anhydrous" complex of potassium enolate, K+[CH2(CO)CH3]–·5DMSO, to the triple bond of phenylacetylene is estimated to be ∆H‡ = 15.7 kcal/mol, ∆G‡ = 23.4 kcal/mol that is lower (by ∆∆H‡ = 1.0 kcal/mol, ∆∆G‡ = 1.2 the kcal/mol) than the vinylation barrier in complex 7 containing a water molecule. Indeed, the presence of a water molecule stabilizes the sodium enolate complex, K+[CH2(CO)CH3]–·5DMSO, in a larger extent than the corresponding transition state (Table 4).



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Table 4. Relative enthalpies of reagents (HR) and transition states (HTS) and enthalpies and free

activation

energies

in

K+[CH2(CO)CH3]–·5DMSO,

kcal/mol

of

nucleophilic

addition

K+[CH2(CO)CH3]–·H2O·5DMSO

7,

of

the

complexes

K+[CH2(CO)CH3]–

·HOtBu·5DMSO 8 to phenylacetylene. K+[CH2(CO)CH3]–·5DMSO·nHOR + PhCCH n

HOR

HR

HTS

∆ H‡

∆G‡

0

–

0.0

15.7

15.7

23.4

1

H2 O

–8.7

9.1

17.8

24.6

HOtBu

–3.3

12.1

15.4

21.3

On the contrary, a molecule of tert-butyl alcohol, provides better stabilization of the transition state when compared to the potassium enolate complex, K+[CH2(CO)CH3]–·5DMSO, (Table 4) that decreases the activation barrier of vinylation reaction in the presence of HOtBu. Protonation of carbanions 9, 10, 11 and 12 affording Z-5-phenylpent-5-en-2-one complexes, PhCH=CH-CH2(CO)CH3·NaOH·4DMSO Z-13, PhCH=CH-CH2(CO)CH3·NaOtBu·4DMSO Z-14, PhCH=CH-CH2(CO)CH3·KOH·5DMSO Z-15, PhCH=CH-CH2(CO)CH3·KOtBu·5DMSO Z-16, is associated with significant decrease in enthalpy (by 29.5 kcal/mol, 17.9 kcal/mol, 21.4 kcal/mol and 20.3 kcal/mol, Fig. 5) and completes the reaction of nucleophilic addition of acetone to phenylacetylene with regeneration of a superbase. The experimentally observed formation of only E-isomers of 5-phenylpent-5-en-2-ones is due to further rotational Z-E-isomerization of the PhCHin anionic form [PhCH-CH=CH(CO)CH3]– (the mechanism of this isomerization was studied in detail in our article21), which additionally decreases enthalpy of the system during the formation of complexes E-13, E-14, E-15 and E-16 by 3.0 kcal/mol, 4.1 kcal/mol, 3.4 kcal/mol and 3.5 kcal/mol, respectively (Fig. 5).

4. CONCLUSIONS Energy profiles obtained for the C-vinylation of acetone with phenylacetylene in the presence of superbases, represented by the complexes MOH·nDMSO and tBuOM·nDMSO, indicate that the nucleophilic addition of the acetone anions to the phenylacetylene molecule is the rate-determining stage of reactions under investigation. The calculated activation energies of this reaction stage decrease upon transition from systems based on alkali metal hydroxides to those derived from tertbutoxides, which is in good agreement with experimentally observed increase in yields of acetone vinylation products in the series of superbasic systems NaOH/DMSO (10%) < KOH/DMSO (20%) < KOtBu/DMSO (70%).


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While the initial solvate complexes of potassium and sodium hydroxides and tert-butoxides are structurally and compositionally similar, the structure of MOH/DMSO and tBuOM/DMSO reaction centers becomes noticeably different during the course of the reaction. The formation of complexes of acetone anions under the action of both types of superbases occurs with similar activation barriers. However, in the case of alkali metal hydroxides, the water molecules formed can hydrate the initial nucleophile, reducing its activity, the activation barrier of nucleophilic addition to phenylacetylene increases due to a higher stabilization of the starting reagents relative to the corresponding transition state. A molecule of tert-butyl alcohol binds the formed nucleophilic particle to a lesser extent, moves easily to the outer coordination sphere and does not prevent stabilization of the transition state with metal cation at the stage of the nucleophilic addition to phenylacetylene. As a whole, this decreases activation barrier of the vinylation reaction in the presence of HOtBu.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI:

Complete ref 31, calculated imaginary frequencies of all transition states species, and tables of Cartesian coordinates and electronic energies for all of the calculated structures and a description of Wertz26 entropy correction for dimethyl sulfoxide (PDF)

AUTHOR INFORMATION Corresponding Author * Tel.: +7-3952-422-423; Fax: +7-3952-419-346; E-mail: boris_troﬁ[email protected] ORCID Boris A. Troﬁmov: 0000-0002-0430-3215 NOTES The authors declare no competing financial interest. ACKNOWLEDGMENTS V.O. gratefully acknowledges A.E. Favorsky Irkutsk Institute of Chemistry for the financial support. N.V., V.K., and V.O. gratefully acknowledge Grant No.4.1671.2017/4.6 from the Ministry of education and science of the Russian Federation and RFBR Grant No. 18-03-00573a. Boris Trofimov acknowledges Russian Scientific Foundation (Project No. 14-13-00588).



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Transition-Metal-Free C-Vinylation of Ketones with Acetylenes: A

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