Addition of α-halocarboxylic acid esters to para-substituted benzaldehydes in the presence of pentacarbonyliron

Article abstract of DOI:10.1023/A:1013175403637

Pentacarbonyliron promotes addition of α-halocarboxylic acid esters at the carbonyl group of benzaldehyde and its para-substituted analogs. The substituent in the benzene ring strongly affects the process.

Full text of DOI:10.1023/A:1013175403637

Russian Journal of Organic Chemistry, Vol. 37, No. 9, 2001, pp. 1273 1275. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 9, 2001,
pp. 1341 1343.
Original Russian Text Copyright
2001 by Terent’ev, Vasil’eva, Kuz’mina, Mysova, Chakhovskaya.
Addition of -Halocarboxylic Acid Esters to para-Substituted
Benzaldehydes in the Presence of Pentacarbonyliron
A. B. Terent’ev, T. T. Vasil’eva, N. A. Kuz’mina,
N. E. Mysova, and O. V. Chakhovskaya
Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 117813 Russia
fax: (095)1355085; e-mail: terent@ineos.ac.ru
Received September 20, 2000
Abstract Pentacarbonyliron promotes addition of -halocarboxylic acid esters at the carbonyl group of
benzaldehyde and its para-substituted analogs. The substituent in the benzene ring strongly affects the process.
We previously showed [1, 2] that Fe(CO)5 is
an efficient promotor of Reformatsky type reactions.
In some cases the yield of the adducts attained 80
Esters I III readily reacted with aldehydes IVa
IVc to give the corresponding hydroxy esters Va Vf
in good yields. However, in some cases the reactions
95%. In the present work we studied the effect of with p-methoxybenzaldehyde resulted in formation of
para-substituent in benzaldehyde on its reactions with
methyl bromoacetate (I), methyl -bromopropionate
(II), and methyl trichloroacetate (III) in the presence
of pentacarbonyliron. Benzaldehyde (IVa), p-chloro-
benzaldehde (IVb), and p-methoxybenzaldehyde
(IVc) were involved in the reaction. The molecule of
ester II contains a chiral center. For that reason we
also tried to find conditions allowing the reaction of
II with aldehydes to be performed in an inert solvent
with a minimal amount of HMPA at room temperature
(with a view to accomplish stereoselective syntheses).
The reactions of esters I III with benzaldehyde were
studied in [2, 3].
acrylic acid derivatives VI instead of the expected
hydroxy esters V, presumably due to elimination of
water (or HOCl) during the process (Scheme 1).
The reactions of methyl bromoacetate (I) with
aldehydes IVa and IVb at 130 C (in chlorobenzene)
afforded hydroxy esters V, while in the reaction with
aldehyde IVc unsaturated ester VIa was isolated.
Similar results were obtained in the reactions of
methyl -bromopropionate (II) and methyl trichloro-
acetate (III) with aldehydes IVa IVc at 80 C
(in boiling benzene) and at room temperature in the
presence of HMPA. Presumably, the effect of para-
methoxy group (compound IVc) in the reactions
Scheme 1.
I, R = Y = H, X = Br; II, R = Me, X = Br, Y = H; III, R = X = Y = Cl; IV, Z = H (a), Cl (b), MeO (c); V, R = Y = H,
Z = H (a); R = Y = H, Z = Cl (b); R = Me, Y = H, Z = H (c); R = Me, Y = H, Z = Cl (d); R = Y = Cl, Z = H (e); R = Y = Cl,
Z = Cl (f); VI, R = H, Z = MeO (a); R = Me, Z = MeO (b); R = Cl, Z = MeO (c).
1070-4280/01/3709-1273$25.00 2001 MAIK Nauka/Interperiodica

1274
TERENT’EV et al.
Scheme 2.
with -haloesters originates from the ability of the
methoxy group to stabilize the carbocationic center
formed via elimination of OH and H or OH and Cl
species.
It should be emphasized that just the use of HMPA
as co-catalyst in combination with Fe(CO)5 allowed
us to carry out the reaction of prochiral methyl bromo-
propionate II with aldehydes IVa IVc under as mild
conditions as possible (as applied to the given type
of the process), i.e., in benzene at room temperature.
mediate adduct reacts with aldehyde, yielding iron
alkoxide; hydrolysis of the latter (on treatment with
dilute hydrochloric acid) leads to formation of the
final product (Scheme 2). Electon-donor substituent in
the aldehyde creates most unfavorable conditions for
intramolecular attack on the CHO group by the
anionic center formed by reduction of the initial
radical species.
Thus, we revealed an unusual effect of the para-
methoxy group in the reaction of substituted benz-
aldehydes with -halocarboxylic acid esters in the
presence of Fe(CO)5: The reactions with benzaldehyde
and p-chlorobenzaldehyde yield the corresponding
hydroxy esters, whereas from p-methoxybenzaldehyde
acrylic acid derivatives are formed.
With the goal of finding conditions for stereoselec-
tive synthesis of hydroxy esters and their derivatives
we examined the reaction with aldehydes of (4R)-3-
(2-bromopropionyl)-4-phenyltetrahydrooxazol-2-one
(VII) as initial bromide. Compound (VII) was syn-
thesized by acylation of (R)-4-phenyltetrahydrooxazol-
2-one with 2-bromopropionyl bromide [4]. However,
unlike the corresponding ester II, amide VII turned
out to react quite differently under the same condi-
tions. No adducts like V or VI were formed when the
reaction was performed in boiling benzene or in the
presence of HMPA at room temperature. Moreover,
the reaction of -bromo ester II with benzaldehyde in
the presence of 10% of amide VII gave neither adduct
Vb nor VIb; this result suggests that amide VII
inhibits the main process. On the other hand, heating
of amide VII in benzene THF (10:1) under reflux
in the presence of an equimolar amount of Fe(CO)5
(no aldehyde added) resulted in reduction (with
elimination of bromine) and/or stereoselective reduc-
tive dimerization of the amide [4].
It should be noted that the substituent nature does
not affect Reformatsky type reactions [5] a priori
involving intermediate formation of organometallic
compounds which then react with substituted benz-
aldehydes. By special experiments we showed [2] that
the reaction of ester II with Fe(CO)5 gives no organo-
iron compound or at least it does not accumulate in
the reaction mixture. Nevertheless, the mechanism
of the process under study undoubtedly includes
oxidative addition of the organic substrate to penta-
carbonyliron. At this stage the equilibrium is likely
to be displaced toward initial compounds. The inter-
EXPERIMENTAL
The mass spectra were obtained on a Finnigan
MAT Magnum GC MS system using a 25-m Ultra-2
column; the oven temperature was programmed from
30 to 220 C at a rate of 2.5 deg/min. GLC analysis
was performed on an LKhM-80 chromatograph using
a 1300 3-mm steel column packed with 15% of
SKTFT-50Kh on Chromaton-N-AW; carrier gas
helium, flow rate 60 ml/min; thermal conductivity
detector; oven temperature programming from 50 to
1
250 C at a rate of 6 deg/min. The H and 13C NMR
spectra were recorded on a Bruker WP-200 instrument
(200 MHz) using CDCl3 as solvent; the chemical
shifts were measured relative to tetramethylsilane.
All organic reagents were purified by distillation;
Fe(CO)5 (Fluka; purity 97%) was used without
additional purification.
Reactions of methyl bromoacetate with benz-
aldehydes in the presence of Fe(CO)5. A solution
of 1 mmol of methyl bromoacetate (I), 1 mmol of
aldehyde IVa IVc, 2 mmol of Fe(CO)5, and 0.01 g
(0.05 mmol) of CBrCl3 in 1 ml of chlorobenzene was
refluxed (130 C) for 4 h. The mixture was treated
with dilute hydrochloric acid and extracted with
benzene, the extract was dried over Na2SO4, and
the solvent and unreacted initial compounds were
distilled off.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001

ADDITION OF -HALOCARBOXYLIC ACID ESTERS
1275
Methyl 3-hydroxy-3-phenylpropionate (Va).
Yield 41% [3].
aldehyde IVa IVc, and 2 mmol of Fe(CO)5 in 1 ml
of benzene was refluxed (80 C) for 2 h (method a) or
was kept for 3 days at room temperature in DMF
(method b). The mixture was then treated as described
above.
Methyl 2-chloro-3-phenylacrylate (method a) [2].
Yield 41%; cis trans ratio 1:5.
Methyl 2,2-dichloro-3-hydroxy-3-phenylpropio-
nate (Ve) (method b) [3]. Yield 30%.
Methyl 3-hydroxy-3-(p-chlorophenyl)propionate
(Vb). Yield 26%. Mass spectrum, m/z (Irel, %): 214
(19) [M]+ , 196 (42) [M OH]+, 165 (90) [M H2O
1
OMe]+, 141 (100) [M CH2COOMe]+. H NMR spec-
trum, , ppm: 2.64 m (2H, CH2), 3.63 s (3H, OMe),
3.92 br.s (1H, OH), 5.04 m (1H, CH).
Methyl p-chlorocinnamate. Yield 3%. Mass
spectrum, m/z (Irel, %): 196 (60) [M]+, 165 (100)
[M OMe]+, 137 (30) [M COOMe]+, 85 (1).
Methyl 2-chloro-3-p-chlorophenylacrylate
1
(method a). Yield 50%; cis trans ratio 1:5. H NMR
Methyl p-methoxycinnamate (VIa). Yield 31%.
Mass spectrum, m/z (Irel, %): 192 (80) [M]+ , 161
(100) [M OMe]+, 133 (30) [M COOMe]+, 118 (8),
spectrum, , ppm: 3.71 s, 3.85 s (3H, OCH3); 7.77 s,
7.81 s (1H, CH); 7.29 7.32 m (5H, Harom). Mass
spectrum, m/z (Irel, %): 230 (95) [M]+ , 199 (40)
[M OMe]+, 195 (100) [M Cl]+, 171 (20) [M
COOMe]+.
Methyl 2,2-dichloro-3-(p-chlorophenyl)-3-hy-
droxypropionate (Vf) (method b). Mass spectrum,
m/z (Irel, %): 282 (0) [M]+ , 265 (1) [M OH]+, 237
(25) [M OH CO]+, 141 (100) [CCl2COOMe,
ClC6H4CHOH]+, 113 (30) [CCl2OMe]+, 77 (85)
[C6H5]+.
Methyl 2-chloro-3-p-methoxyphenylacrylate
(VIc) (method a). Yield 50%; cis trans ratio 1:4.5.
1H NMR spectrum, , ppm: 3.80 s, 3.84 s (6H,
OCH3); 6.88 s, 6.92 s (1H; CH); 8.27 8.30 m (5H,
Harom). Mass spectrum, m/z (Irel, %): 226 (100) [M]+ ,
195 (30) [M OMe]+, 191 (35) [M Cl]+, 167 (15)
[M COOMe]+.
1
102 (5). H NMR spectrum, , ppm: 3.77 s, 3.81 s
(6H, OCH3); 6.26 d, 6.34 d, 7.60 d, 7.69 d (1H, CH,
J = 4 Hz; Jtrans = 53 Hz); 6.85 d, 6.89 d
(1H, CH, J = 2 Hz, Jcis = 24 Hz).
Reactions of methyl 2-bromopropionate with
benzaldehydes in the presence of Fe(CO)5. A solu-
tion of 1 mmol of methyl 2-bromopropionate (II),
1 mmol of aldehyde IVa IVc, 2 mmol of Fe(CO)5,
and 2 mmol of HMPA in 1 ml of benzene was kept
for 5 days at room temperature. The mixture was then
treated as described above. The ratio of diastereo-
isomers was determined from the 1H NMR spectra.
Methyl 3-hydroxy-2-methyl-3-phenylpropionate
(Vc). Yield 54% [3]. Diastereoisomer ratio 1.5:1.
1H NMR spectrum, , ppm: 0.95 d, 0.98 d; 1.09 d,
1.12 d (3H, CH3CH, J = 8.7 Hz); 2.75 br.s (1H, OH);
3.61 s, 3.67 s (3H, CH3O); 4.75 m; 5.07 m (1H, CH);
7.3 m (Harom).
REFERENCES
Methyl 3-(p-chlorophenyl)-3-hydroxy-2-methyl-
propionate (Vd). Yield 69%. Diastereoisomer ratio
1.5:1. Mass spectrum, m/z (Irel, %): 228 (5) [M]+ ,
210 (3) [M H2O]+ , 197 (1) [M OMe]+, 141, 143
(42) [ClC6H4CHOH]+, 88 (100) [CH3CH2COOMe]+ .
1H NMR spectrum, , ppm: 0.95 d, 0.98 d; 1.09 d,
1.12 d (3H, CH3CH, J = 7.9 Hz); 2.75 br.s (1H, OH);
3.61 s, 3.67 s (3H, CH3O); 4.75 m, 5.07 m (1H, CH),
7.3 m (Harom).
Methyl 3-p-methoxyphenyl-2-methylpropenoate
(VIb). Yield 25%. Mass spectrum, m/z (Irel, %):
206 (100) [M]+ , 175 (38) [M H2O OMe]+, 147
(43) [M H2O COOMe]+, 146 (75) [MeOC6H4-
CH C CH2]+ .
1. Terentiev, A.B., Vasilieva, T.T., Kuz’mina, N.A.,
Mysov, E.I., Kuznetzov, N.Yu., and Belokon’, Yu.N.,
J. Chem. Res., Synop., 1998, p. 306; M., pp. 1281
1289.
2. Terent’ev, A.B., Vasil’eva, T.T., Kuz’mina, N.A.,
Mysov, E.I., Kuznetsov, N.Yu., and Belokon’, Yu.N.,
Izv. Ross. Akad. Nauk, Ser. Khim., 1999, no. 6,
pp. 1132 1138.
3. Terent’ev, A.B., Vasil’eva, T.T., Kuz’mina, N.A.,
Chakhovskaya, O.V., Brodskii, E.S., and Belo-
kon’, Yu.N., Izv. Ross. Akad. Nauk, Ser. Khim., 2000,
no. 4, pp. 718 720.
4. Kuznetsov, N.Yu., Khrustalev, V.N., Terent’ev, A.B.,
and Belokon’, Yu.N., Izv. Ross. Akad. Nauk, Ser.
Khim., 2001, no. 3, pp. 525 528.
Reactions of methyl trichloroacetate with benz-
aldehydes in the presence of Fe(CO)5. A solution
of 1 mmol of methyl trichloroacetate (III), 1 mmol of
5. Zhang, Y. and Wu, W., Tetrahedron: Asymmetry,
1997, vol. 8, no. 21, pp. 3575 3579.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001