Triethylamine-promoted elimination from (R,R)-PhCHORCHClCO2Me (R = MeCO, PhCO, 4-MeC6H4, 4-MeOC6H4, MeSO2 and 4-MeC6H4SO2) in various solvents

Article abstract of DOI:10.1039/a806946h

The rates and stereochemistry of elimination from a number of (R,R)- PhCHORCHClCO₂Me (R = MeCO, PhCO, 4-MeC₆H₄, 4-MeOC₆H₄, MeSO₂ and 4- MeC₆H₄SO₂) with trie

Full text of DOI:10.1039/a806946h

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138 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 138±139$
Triethylamine-promoted Elimination from
(R,R)-PhCHORCHClCO2Me (R ˆ MeCO, PhCO,
4-MeC6H4, 4-MeOC6H4, MeSO2 and 4-MeC6H4SO2)
in Various Solvents$
Rosana S. Montani,a Elisabet Gilb and Mercedes C. Cabaleiro*a
aInstituto de Quimica Organica, Universidad Nacional del Sur, 8000 Bahia Blanca, Argentina
bInstituto de Quimica Organica and Area de Fisicoquimica, Universidad Nacional del Sur,
8000 Bahia Blanca, Argentina
The rates and stereochemistry of elimination from a number of (R,R)-PhCHORCHClCO2Me (R ˆ MeCO, PhCO,
4-MeC6H4, 4-MeOC6H4, MeSO2 and 4-MeC6H4SO2) with triethylamine in tetrahydrofuran, acetone, methanol,
dimethylformamide and acetonitrile as solvents led to the conclusion that the elimination process occurs through an
(E1cB)I mechanism.
Kinetic results, together with stereochemical evidence,
obtained from the triethylamine-promoted dehydroacetoxy-
lation from methyl (R,R)-2-chloro-3-acetoxy-3-phenyl-
propanoate (1) in methanol have been interpreted as
proceeding via an E1cB process of the irreversible type.1
We report here an examination of the response of the
elimination to the e€ect of substitution of the acetyl±methyl
portion (1) by some aromatic groups as well as the
behaviour of some related compounds.
ecient values (Table 1) it follows that the relative degree of
reactivity of these compounds is associated with the change
in the dielectric constant of the solvent, which again is in
accordance with the view that the rate-controlling stage
involves an anionic species.4±6 However, the sensitivity of
the reaction rates to the solvent change appears to be less
pronounced with an increase in the inductive stabilising
in¯uence exerted by the 3-substituent on the carbanion. A
likely explanation for this might lie in the assumption that
the anion stabilisation through electrostatic solvation should
become weaker as the electron-attracting power of the
3-substituent dissipates the degree of negative charge
concentration.
Although the structural characteristics of substrates 5
and 6 are not strictly analogous to those of the remaining
compounds, the kinetic evidence (Table 1) seems to suggest
that the previous considerations also apply to them. As
regards the stereochemical outcome of the outcome of the
reactions, the results arising from those carried out in the
less polar solvents (tetrahydrofuran and acetone respect-
ively) show that all the substrates a€ord, exclusively, the
thermodynamically more stable ole®n (Z), which argues in
favour of a carbanionic process.% As to methanol (MeOH),
dimethylformamide (DMF) and acetonitrile (AN) the stereo-
speci®city of the eliminations in these solvents appears to
depend on both the nature of the 3-substituent and the
polarity of the reaction medium. The data in Table 2 reveal
that the product ratio Z:E decreases with increasing di-
electric constant of the solvent. This e€ect is comparable to
that reported for the TEA-mediated elimination from (R,R)-
PhCHORCHClCO2Me (R ˆ Ac, CH2ClCO, CHCl2CO and
CCl3CO), which was rationalised in terms of a polar
solvent-induced increase of the population of the rotational
To obtain further information about these eliminations,
the e€ect of solvents of di€erent dielectric constants upon
both the kinetic and the stereochemical behaviour of the
eliminations was also analysed.
According to the structural analogy between methyl
(R,R)-2-chloro-3-acetoxy-3-phenylpropanoate (1) and com-
pounds 2, 3 and 4, it seems not unreasonable to assume the
involvement of a carbanionic species in the methanolic
triethylamine (TEA)-induced elimination from the latter
substrates. Support for this suggestion is found in a com-
parison of the data recorded in Table 1, which indicates
that the variation in reactivity along the series 1±4 is
qualitatively consistent with that expected on the grounds of
the di€erent stabilizing e€ects of the electron-withdrawing
3-substituent on the rate-determining 2-carbanion for-
mation.1±3 Moreover, from examination of the rate co-
Table 1 Kinetic dataa for elimination from (R,R)-PhCHORCHClCO2Meb with TEAc in various solvents at 30 8C
THF
(7.6e)
Acetone (Acet)
(20.7e)
MeOHd
(31.5e)
DMF
(36.7e)
Acetonitrile (AN)
(37.6e)
R
kAN/kMeOH
kDMF/kAcet
1 Ac
2 PhCO
3 4-MeC6H4CO
4 4-MeOC6H4CO
5 MeSO2
0.05
0.05
0.03
0.02
0.145
0.184
0.043
0.034
0.029
0.021
0.805
1.41
0.104
0.088
0.071
0.049
1.54
0.132
0.113
0.109
0.078
1.73
0.139
0.124
0.120
0.111
1.92
1.34
1.41
1.83
2.27
1.25
1.10
3.07
3.32
3.76
3.90
2.15
1.54
6 4-MeC6H4SO2
2.14
2.19
2.36
1
.
3
3
.
3
ak2 ˆ dm3 mol 1 min
b[Subst.] ˆ 0.003 mol dm
.
c[TEA] ˆ 0.06 mol dm
d[TEA] ˆ 0.06 mol dm 3, [TEA±HCl] ˆ 0.03 mol dm
.
eDielectric constant.
*To receive any correspondence.
%The possibility of an E2 mechanism for these compounds can be
dismissed on the basis that the eliminations a€ord exclusively or
predominantly the Z ole®n, which is not what should be predicted
for a concerted pathway.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).

View Article Online
J. CHEM. RESEARCH (S), 1999 139
conformer of the intermediate carbanion with a geometry
closely related to that of the (E)-ole®n.1
Table 2 Olefinic product distribution (Z:E) for the elimination
from (R,R)-PhCHORCHClCO2Me in various solvents
Compd. THF
Acetone
MeOH
DMF
AN
1
2
3
4
5
6
100:00
100:00
100:00
100:00
100:00
100:00
100:00
98:02
98:02
100:00
100:00
100:00
100:00
76:24
81:19
84:16
86:14
97:03
98:02
63:37
66:34
81:19
85:15
93:07
96:04
100:00
100:00
100:00
100:00
100:00
(Found: C, 63.9; H, 4.8; Cl, 10.2. C17H15ClO4 requires C, 64.1;
H, 4.7; Cl, 11.2%); d (ppm) (CCl4) 7.85 (2H, m), 7.20 (8H, m), 5.90
(1H, d), 4.34 (1H, d) and 3.38 (3H, s). Methyl (R,R)-2-chloro-3-(4-
methylbenzoyloxy)-3-phenylpropanoate (Found: C, 65.0, H, 5.2; Cl,
10.4. C18H17ClO4 requires C, 65.0, H, 5.15; Cl, 10.65%); d (ppm)
(CCl4) 7.72 (2H, d), 7.12 (5H, m), 6.78 (2H, d), 5.88 (1H, d), 4.32
(1H, d), 3.45 (3H, s) and 2.22 (3H, s). Methyl (R,R)-2-chloro-3-(4-
methoxybenzoyloxy)-3-phenylpropanoate (Found: C, 61.5; H, 4.8; Cl,
10.0. C18H17ClO5 requires C, 2.0; H, 4.9; Cl, 10.2%); d (ppm)
(CCl4) 7.58 (2H, d), 6.95 (5H, m), 6.48 (2H, d), 5.82 (1H, d), 4.22
(1H, d), 3.35 (3H, s) and 3.27 (3H, s). For the preparation of
Methyl (R,R)-2-chloro-3-tosyloxy-3-phenylpropanoate, tosyl chloride
(13.2 mmol) was slowly added to a solution of methyl (R,R)-
2-chloro-3-hydroxy-3-phenylpropanoate (11.6 mmol, 36 cm3) in
pyridine±dichloromethane (1:1) at 0 8C. The mixture was stored at
0 8C for 6 days and then worked-up as described for the aroyl
derivatives (Found: C, 55.1; H, 4.8; Cl, 9.4. C17H17ClO5S requires
C, 55.4; H, 4.2; Cl, 9.5%); d (ppm) (CCl4) 7.22 (2H, d), 7.09 (5H,
s), 6.86 (2H, d), 5.48 (1H, d), 4.20 (1H, d), 3.58 (3H, s), 2.24 (3H, s).
Methyl (R,R)-2-chloro-3-mesyloxy-3-phenylpropanoate was obtained
following the procedure described for the tosyl derivative (Found:
C, 45.3; H, 4.45; Cl, 12.0. C11H13ClO5S requires C, 45.1; H, 4.5; Cl,
12.11%); d (ppm) (CCl4) 7.15 (5H, m), 5.48 (1H, d), 4.30 (1H, d),
3.58 (3H, s), and 2.08 (3H s).
Kinetic Procedure.ÐRates were measured at 3020.05 8C. The
reactions were started by adding a solution of TEA (12 mmol,
100 cm3) to a solution of the corresponding substrate (0.6 mmol) in
the appropriate solvent. In the case of MeOH the basic solution
also contained TEA±HCl (6 mmol). The progress of the reaction
was checked by quenching aliquots (40 cm3) in water acidi®ed
with hydrochloric acid and extracted with dichloromethane. The
worked-up fractions were analysed by 1H NMR integration. The
total area corresponding to the aromatic region minus that due to
the unreacted material, as estimated from the area under the
aliphatic proton signals, gave the area arising from the aromatic
protons of the elimination product. Second-order rate constants
were obtained in the usual way from those of pseudo-®rst order.
Product Analysis.ÐThe product compositions were estimated by
1H NMR integration of the areas under the methoxy carbonyl
signals for reaction mixtures quenched after eight half-lives.
On the other hand, the decrease in the proportion of the
(E)-ole®n formed along the series 1, 5, 6 in MeOH, DMF
and AN, respectively, is qualitatively analogous to the
sequence previously found for TEA-induced elimination
from methyl (R,R)-2-chloro-3-bromo-3-phenylpropanoate
with a similar change of solvents.4 This was interpreted as a
function of the ability of the 3-substituent to increase the
lifetime of the intermediate and hence to enhance the possi-
bility to attain the appropriate geometry leading to the ther-
modynamically favoured ole®n (Z). However, a di€erent
trend emerges from comparison of the results arising from
compounds 1, 2, 3 and 4, which indicates a negative corre-
lation between the Z:E ratio and the electron-attracting
eciency of the 3-substituent. If the degree of (E)-ole®n
formation were to re¯ect only the in¯uence of the factors
that seem to govern the rate-controlling pathway, then the
sequence of the relative e€ect of the 3-substituent upon the
stereospeci®city of the elimination for the whole series of
compounds should be comparable to that on the reaction
rate. An important factor that possibly in¯uences the ®nal
stereochemistry, which should be considered at this stage of
the elimination process, is the leaving power of the depart-
ing 3-group. Inspection of the data in Table 2 indicates that
the stereospeci®city of the reactions for the series 1±4
increases with decreasing leaving group ability. A justi®ca-
tion for this observation could be found in the fact that
reluctant leaving groups will allow the intermediate to select
the route to the more stable ole®n. Thus, the increase in the
Z-proportion obtained in MeOH, DMF and AN appears to
be favoured when the factors that enhance the lifetime of
the carbanion are dominant. For the intermediate cases,
however, the e€ect of the solvent polarity seems to be mani-
fested. Therefore, the stereochemical evidence obtained for
the elimination of the present series of compounds might
partly be accounted for on the grounds of the simultaneous
operation of three main factors that govern the product-
forming pathway: (i) the carbanion stabilising power of
the 3-substituent, (ii) its departing capability, and (iii) the
in¯uence of the solvent polarity; the combination of these
factors results in the observed stereochemistry.
Received, 7th September 1998; Accepted, 20th October 1998
Paper E/8/06946H
References
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Experimental
1H NMR spectra were recorded with a Varian EM 360L instru-
ment. Compound 1 was obtained as described in the literature.1
The aroyl derivatives 2, 3 and 4 were prepared by the reaction
of methyl (R,R)-2-chloro-3-hydroxy-3-phenylpropanoate (7.7 mmol)
with the corresponding aroyl chloride (10.5 mmol) in dry pyridine
(20 cm3) at 30 8C. After the reaction was complete (25±30 h) the
mixture was poured into
a
10% HCO3Na solution (20 cm3),
extracted with chloroform (3Â 10 cm 3) and washed with water.
The solvent was removed under reduced pressure and the residue
puri®ed by recrystallisation from methanol. Analytical data were
as follows: Methyl (R,R)-2-chloro-3-benzoyloxy-3-phenylpropanoate