Journal of Computational Methods in Molecular Design, 2015, 5 (3):150-154

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Understanding, the regio- and stereoselective in McKenna Reaction using

DFT calculation
Abdellah Zeroual1*, Ali Barhoumi2, Redouan Hammal1, Salem Bakkas2
and Abdeslam El Hajbi1
1

Physical Chemistry Laboratory, Department of Chemistry, Faculty of Science, Chouab Doukkali University, El
Jadida, Morocco
2
Laboratory of Organic and Bioorganic Chemistry and Environment, Department of Chemistry, Faculty of Science,
Chouab Doukkali University, El Jadida, Morocco
_____________________________________________________________________________________________
ABSTRACT
In this study, we used DFT B3LYP/6-31G(d) to determine certain thermodynamic properties, global indices and
chemical potentials of the reaction between phosphine and bromotrimethylsilane (McKenna Reaction). Our results
show that phosphine behaves as a nucleophile, while bromotrimethylsilane behaves as an electrophile. The
nucleophilic attack takes place preferentially at the oxygen atom of the double bond of phosphine. The reaction is
exothermic, regioselective and stereoselectivite.
Keywords: DFT B3LYP/ 6-31(d), regioselectivity, stereoselectivity, nucleophilicity, Parr functions.
_____________________________________________________________________________________________
INTRODUCTION
Phosphonic acids having a hetero atom in position and have attracted much attention in recent years because
they are involved in many biological processes such inhibitors, these compounds have been widely applied in
medicine and biochemistry, as antibacterial agents, enzymes renin, thrombin, and anti-HIV agents. [1]
Acid bis-naphthyl -ketophosphonate, for example, appears as a new non-peptide inhibitor of neutrophil cathepsin G
(Ki = 38M) and chymase (Ki = 2,3M). [2] The glutamyl--ketophosphonate adenosine (Glu-KPA) is a
competitive inhibitor of glutamyl-tRNA synthetase from Escherichia coli (GluRS) with the Ki 18m, while the , difluoro--cetophosphonates serve as 'effective inhibitors of protein tyrosine phosphatase. [3]
Regarding similar --ctophosphonates of glutarate, they are known to inhibit the activity of the isolated ctoglutaratedshydrognase complex from the brain and cultured cells. [4]
For these reasons, the development of simple and stereoselective methods to prepare phosphonates has become
important in organic synthesis. [5] Even though there are numerous methods for their syntheses, [6] those relying on
the formation of silicon-phosphorous bonds by transition metal catalyzed cross coupling or addition reactions are
particularly noteworthy due to their overall efficiency and selectivity. [7] Our aim in this work is to present a
theoretical study of McKenna Reaction, Which Oxygen Attacks Bromotrimethylsilane? (Figure 1) and compared the
results of our calculations with experimental results available in the literature. [8]

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J. Comput. Methods Mol. Des., 2015, 5 (3):150-154
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TS1

O
H3C
H3CO

Si(CH3)3
O
H3C
P (S) + CH3Br
*O
H3CO

P1

P + Br Si
TS2

O
2

H3C

P (R) + CH3Br
*
H3CO
O Si(CH3)3

P2

Fig. 1: Reaction between bromotrimethylsilane

MATERIALS AND METHODS

COMPUTATIONAL METHODS
DFT computations were carried out using the B3LYP functional, [9] together with the standard 6-31G basis set.
[10] The optimizations were carried out using the Berny analytical gradient optimization method. [11] The
stationary points were characterized by frequency computations in order to verify that TSs have one and only one
imaginary frequency. The IRC paths [12] were traced in order to check the energy profiles connecting each TS to
the two associated minima of the proposed mechanism using the second order GonzlezSchlegel integration
method. [13]
Solvent effects of acetonitrile were taken into account through single point energy calculations using the polarisable
continuum model (PCM) as developed by Tomasis group [14] in the framework of the self-consistent reaction field
(SCRF). [15] The electronic structures of stationary points were analyzed by the natural bond orbital (NBO) method.
[16] All computations were carried out with the Gaussian 09 suite of programs. [17] The global electrophilicity
index [18] , is given by the following expression, = ( 2/2), in terms of the electronic chemical potential and
the chemical hardness . Both quantities may be approached in terms of the one-electron energies of the frontier
molecular orbital HOMO and LUMO, eH and eL, as = (eH - eL)/2 and = (eL - eH), respectively. [19] Recently,
we introduced an empirical (relative) nucleophilicity index N, [20] based on the HOMO energies obtained within the
KohnSham scheme, [21] and defined as N = EHOMO(Nu) - EHOMO(TCE). The nucleophilicity is referred to
tetracyanoethylene (TCE), because it presents the lowest HOMO energy in a large series of molecules already
investigated in the context of polar cycloadditions. This choice allows us to handle conveniently a nucleophilicity
scale of positive values. Electrophylic
and nucleophilic
Parr functions, [22] were obtained through the
analysis of the Mulliken atomic spin density (ASD) of the radical anion and radial cation of the reagents. The local
electrophilicity indices and local nucleophilicity indices, [22] were evaluated using the following expressions: k =
.
, Nk= N.
. [22]
RESULTS AND DISCUSSION
3.1. Analysis of the reactivity indices of the reactants.
The static global properties, namely electronic chemical potential , chemical hardness , global electrophilicity
index and global nucleophilicity index N of phosphite and bromotrimethylsilane are the chemical properties which
we used to analyse reactivity at the various sites in the reactants (Table1).
Table 1: DFT/B3LYP/6-31G(d) Electronic chemical potential, , chemical hardness, , electrophilicity , and nucleophilicity N values, in
eV

phosphite
Bromotri-methylsilane

6.90
8.08

-3.43
-3.52

0.85
0.76

N
2.64
1.96

We can deduce from table 1 that:

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The electronic chemical potential of phosphite is greater than that of the bromotrimethylsilane, which implies that
electron transfer takes place from phosphite to the bromotrimethylsilane.
The nucleophilicity index of the phosphite (2.64 eV) is greater than that of the bromotrimethylsilane (1.96 eV),
implying that in this reaction phosphite behaves as a nucleophile while the bromotrimethylsilane behave as
electrophiles.
3.2. Prediction of the regioselectivity of the reaction using local electrophilicity and local nucleophilicity
indices.
According to Chattaraj's polar model, the local philicity indices (k and Nk) can be used to reliably predict the most
favoured interaction between two polar centres.24,25 The most favourable attack is that which is associated with the
highest local electrophilicity index k of the electrophile and the highest local nucleophilicity index Nk of the
nucleophile. We calculated the values Nk for phosphite and k for bromotrimethylsilane in order to predict the most
likely electrophile/nucleophile interaction throughout the reaction pathway and so explain the regioselectivity of the
reaction.

O P (O1)= 0.94
N1=2.48
-

H 3C
H3CO P

P+(Br)= 0.16
Br W(Br)=0.13
Si

O
H 3C

P (O2)= 0.02
N2=0.05

P+(Si)=0.80
W(Si)=0.68

Figure 2: Local nucleophilicity Nk (eV) of phosphine and local electrophilicity k (eV) of bromotrimethylsilane
The silane atom of bromotrimethylsilane is the most electrophilic active site (Si= 0.68 eV). The O1 (NO1= 2.48 eV) atom of the double
bond of phosphine is more nucleophilic and more active than O2 (NO2= 0.05 eV) atom. Figure 2 shows the most active sites of phosphine
and bromotrimethylsilane. We can therefore deduce that the most favored interaction will take place between the O1 atom of the double
bond of phosphine and the Si atom of bromotrimethylsilane.

3.3. Kinetic study of the two modes of attack (Determination of the kinetic parameters).
Calculation of the enthalpies, free energies and entropies of the reactants, the products obtained, TS1 and TS2. Show
that the attack is kinetically preferred at oxygen atom O1 (Table 2). Using the data given in Table 1, we can sketch
the energy profile of the reaction (Fig. 3).
Table 2: B3LYP/ 6-31(d) Gibbs free energies (G in kcalmol-1, enthalpies (H in kcal mol-1), entropies (S in cal mol-1 K-1), and),
computed at gaz and in acetonitrile for the reactions S and R

G#
G
H#
H
S#
S

Reaction S
Gaz
acetinitrile
11.92
10.66
-56.47
-48.94
89.10
87.22
-91.61
+40.78
-30.30
-31.87
9.21
11.33

Reaction R
Gaz
acetinitrile
30.74
22.59
-52.08
-48.31
108.55
101.02
-35.76
+40.78
-27.169
-27.34
10.68
9.33

This shows that: The activation Gibbs free energies corresponding to the attack at the two oxygen atoms O1 and O2
of the phosphine are 11.92 kcal mol1 at O1 and 30.74 kcal mol1 at O2. The difference between the activation Gibbs
free energies of P1 and P2 is around 20.82 kcal mol1, showing that the formation of S isomers is kinetically
preferred to the formation of R isomers. This result is in agreement with experimental results. The formation of P1
and P2 is exothermic, by 56.47 and 48.31 kcal mol1, respectively. The formation of P1 and P2 is
thermodynamically favorable.

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Fig.3: B3LYP/6-31G(d) Gibbs free energy profile (G, in kcal/mol) of the reaction between phosphine and bromotrimethylsilane.
Relative Gibbs free energies, in kcal/mol, are in italics

The geometries of the TSs involved in the regioisomeric pathways of these reactions between phosphine and
bromotrimethylsilane are given in Fig. 4. The lengths of the O1Si and CBr forming bonds at the configuration R
are 3.026 and 2.001 A, while the lengths of the O2Si and CBr forming bonds at the configuration S are 3.312 and
2.643 A. Some appealing conclusions can be drawn from these geometrical parameters: (i) the most favourable
configuration R is more asynchronous than the configuration S; (ii) the TSs involved in the configuration R
reaction are more asynchronous than those involved in the configuration S.

Fig. 4: Geometries of the TSs involved in the regioisomeric pathways associated between phosphine and bromotrimethylsilane. Distances
are given in Angstroms

CONCLUSION
The regio- and stereoselectivity of the reaction between phosphine and bromotrimethylsilane was studied using
DFT/B3LYP/6-31G(d). Analysis of the global electrophilicity and nucleophilicity indices showed that phosphine
behaves as a nucleophile, while bromotrimethylsilane behaves as an electrophile. The regioselectivity found
experimentally was confirmed by local indices of electrophilicity and nucleophilicity k and Nk. Calculation of the
transition states shows that the formation of the product S is most favored than product R.
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