The efficient allylations of 2-oxocarboxylic acids. Synthesis of 2-allyl derivatives of 2-hydroxycarboxylic acids

Article abstract of DOI:10.1055/s-2002-22710

2-Oxocarboxylic acids or their sodium salts undergo indium-mediated allylation with allyl bromide cinnamyl bromide and ethyl 4- bromocrotonate to provide the corresponding 2-allyl derivatives of glycolic lactic mandelic and malic acids. In the case of rea

Full text of DOI:10.1055/s-2002-22710

LETTER
573
The Efficient Allylations of 2-Oxocarboxylic Acids. Synthesis of 2-Allyl
Derivatives of 2-Hydroxycarboxylic Acids
Synthesis of
2
u
D
eriva
b
tive
s
of 2-H
o
ydroxycarbo
d
xylic
A
cids h Kumar,* Pervinder Kaur, Swapandeep Singh Chimni
Department of Chemistry, Guru Nanak Dev University, Amritsar -143 005, India
E-mail: subodh.kumar@angelfire.com
Received 11 February 2001
hydroxycarboxylic acids 3g–i but the diastereoselectivity
is lowered to 86:14 (3g, 3i) and 90:10 (3h). In the case of
3h after crystallization the diastereomeric ratio could be
increased to 98:2 Therefore allylation with cinnamyl bro-
Abstract: 2-Oxocarboxylic acids or their sodium salts undergo in-
dium-mediated allylation with allyl bromide cinnamyl bromide and
ethyl 4- bromocrotonate to provide the corresponding 2-allyl deriv-
atives of glycolic lactic mandelic and malic acids. In the case of re-
actions with cinnamyl bromide or ethyl 4-bromocrotonate high mide proceeds in a highly diastereoselective manner with
diastereoselectivity is achieved.
ethyl 4-bromocrotonate the diastereoselectivity is lower.
Key words: allylation reactions, hydroxycarboxylic acids, diaste-
reoselective
Table 1 Reactions of 2-Oxocarboxylic Acids 1 with Allyl
Bromides 2
The protonolysis of organometallic reagents by substrates
possessing labile protons is the most detrimental aspect in
carrying out allylation and other organometallic additions.
In recent years indium mediated allylation1 of C = X
(X = O NR) moiety in presence of alcohol,2,3 phenol4 or
active methylene functionalities5 have enormously in-
creased the score of allylation reaction. Also indium me-
diated reactions show better chelation control2a in water
than that attained with magnesium chromium and copper
reagents in anhyd medium. Recently mixed bimetal sys-
tems [BiCl3 Zn(0), BiC13 Mg(0)]6 or presynthesized allyl
boronates,7 and allylsilanes8 have been applied in the ally-
lation of 2-oxocarboxylic acids. Here we report that indi-
um mediated Barbier allylation of 2-oxocarboxylic acids
or their sodium galts with allylbromides 2a–c proceeds ef-
ficiently in THF–H2O (2:1) to provide 2-allyl derivatives
of glycolic lactic mandelic and malic acids. Cinnamyl
bromide and ethyl 4-bromocrotonate provide diastereose-
lective allylation and the -addition product is always iso-
lated.
Entry Reactants R1
R2
Prod- Yield dr
uct
3a
3b
3c
3d
3e
3f
(%)
70
86
66
86
96
95
66
97
96
1
2
3
4
5
6
7
8
9
1a and 2a
H
H
-
1b and 2a C6H5
1c and 2a CH3
H
-
H
-
1d and 2a CH2-CO2H
H
-
1a and 2b
1b and 2b C6H5
1a and 2c
H
C6H5
C6H5
CO2C2H5
CO2C2H5
CO2C2H5
>98:2
>98:2
86:14
90:10
86:14
H
3g
3h
3i
1b and 2c C6H5
1c and 2c CH3
A solution of 1a allyl bromide (2a) and indium metal (sus-
pension) (1:15:1) in THF–H2O (2:1) on stirring at 30 °C
provides9 3a after HCl hydrolysis CHCl3 extraction and
chromatography. Similarly 1b–d with allyl bromide give
2-hydroxycarboxylic acids6,7 3b–d (Table 1) in moderate
to good yields. In order to extend the score of this reaction
to achieve diasteroselective allylation the reactions of 1
have been performed with cinnamyl bromide and ethyl 4-
bromocrotonate. 2-Oxocarboxylic acids la and 1b under-
go allylation with 2b to provide 3e and 3f in high yield.10
The 1H NMR spectra of these products show that only one
diastereomer is formed. Furthermore 1a–c with ethyl 4-
bromocrotonate (2c) provide the corresponding 2-
a Stereochemistry is not known.
b After single crystallization increases to >98:2
Indium mediated allylations are known to generally pro-
ceed through chelation.2a We envisaged that the 2-oxocar-
boxylates due to the presence of negative charge would
exhibit better chelation and might induce higher diastere-
oselectivity. However sodium pyruvate (4c) did not un-
dergo allylation with 2c in THF–H2O but on controlling
the pH of the reaction mixture between 4.7 0.2,9,11 the al-
lylation proceeded quite smoothly and in a highly diaste-
reoselective manner to provide 3i (Table 2). The yield of
3i was only 50%. On using indium (2 equiv) and 2c (3
equiv), the yield of 3i could be increased to 90%. Similar-
ly 4a and 4b undergo diastereoselective allylation with 2c
Synlett 2002, No. 4, 29 03 2002. Article Identifier:
1437-2096,E;2002,0,04,0573,0574,ftx,en;G18801ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

574
S. Kumar et al.
0.2 to provide 3g and 3h10, respectively
LETTER
(3) Kumar, S.; Kumar, V.; Singh, S.; Chimni, S. S. Tetrahedron
Lett. 2001, 42, 5073.
(4) Kumar, S.; Kumar, V.; Chimni, S. S. J. Chem. Res., Synop.
2000, 314.
(5) (a) Li, C. J.; Lu, Y. Tetrahedron Lett. 1995, 36, 2721.
(b) Fujiwara, N.; Yamamoto, Y. J. Org. Chem. 1999, 64,
4095.
at pH 4.7
(Table 2). These allylation reactions of 4a–c took less
time (4–6 h) für completion than taken for reactions of
1a–c (18–24 h).
Table 2 Reactions of Sodium 2-Oxocarboxylates 4a–c with 2c
(6) (a) Wada, M.; Honna, M.; Kuramoto, Y.; Miyoshi, N. Bull.
Chem. Soc. Jpn. 1997, 70, 2265. (b) Wada, M.; Fukuma, T.;
Morioka, M.; Takahashi, T.; Miyoshi, N. Tetrahedron Lett.
1997, 38, 8045.
(7) (a) Wang, Z.; Meng, X.; Kabalka, G. W. Tetrahedron Lett.
1991, 32, 4619. (b) Wang, Z.; Meng, X.; Kabalka, G. W.
Tetrahedron Lett. 1991, 32, 5677.
(8) Wang, Z.; Xu, G.; Wang, D.; Pierce, M. E.; Confalone, P. N.
Tetrahedron Lett. 2000, 41, 4523.
Entry
Substrate
R1
Product
3g
Yield (%)
dr
(9) General Procedure: The 2-oxocarboxylic acid 1 (0.5 mmol),
allyl bromide (0.75 mmol), indium metal (0.5 mmol) were
taken in THF–H2O (2:1) mixture and the reaction mixture
was stirred at 30 °C until the indium metal dissolved. The
turbid reaction mixture was treated with dilute HCl and
extracted with CHCl3. The solvent was distilled off and the
residue was column chromatographed (silica gel, 60–120
mesh) to isolate the allyl addition product. In the case of
reactions with sodium 2-oxocarboxylate (0.5 mmol), 2 C
(1.5 mmol) and indium (1.0 mmol) the pH (4.7) of the
reaction was controlled initially by addition of HOAc and
during the course of reaction with aq NaOH (2%).
(10) 1 H NMR spectral data for the representative cases are given
here. 3e: 2.18 (s,1 H, OH, exchanges with D2O), 3.86 (dd,
J1 = 7.6 Hz, J2 = 4 Hz, 1 H, CH), 4.59 (d, J = 4 Hz, 1 H, CH),
5.20–5.29 (m, 2 H, =CH2), 6.17–6.32 (m, 1 H, =CH), 7.22–
7.37 (m, 5 H, ArH) (For Na salt: mp >300 °C, found C 61.4;
H 5.1%. C11 H11O3Na requires C 61.7; H 5.1%). 3f: mp
168 °C; 4.39 (s, 1 H, OH, exchanges with D2O), 4.4 (d,
J = 9.5 Hz, 1 H, CH), 4.79–4.99 (m, 2 H, =CH2), 5.89–6.03
(m, 1 H, =CH), 7.19–7.41 (m, 8 H, ArH), 7.72–7.73 (m, 2 H,
ArH) (Found C 76.3; H 5.99%. C17H16O3 requires C 76.1; H
5.97%). 3g : 1.31 (t, J = 7 Hz, 3 H, CH3), 2.09 (s, 1 H, OH,
exchanges with D2O), 3.62 (dd, J1 = 8.4 Hz, J2 = 3.6 Hz,
1 H, CH), 4.20 (s, 1 H, OH, exchanges with D2O), 4.22 (q,
J = 7 Hz, 2 H, OCH2) 4.47 (d, J = 3.6 Hz, 1 H, CH), 5.26–
5.38 (m, 2 H, =CH2), 5.77–6.07 (m, 1 H, =CH) (For Na salt:
mp >300 °C; found C 45.4, H 4.9. C8H11O5Na requires C
45.7; H, 5.2%). 3 h: mp 97–98 °C; 1.29 (t, J = 7.2 Hz,
3 H,CH3), 2.20 (s, 1 H, OH, exchanges with D2O), 4.14 (d,
J = 8.2 Hz, 1 H, CH), 4.22 (q, J = 7.2 Hz, 2 H, OCH2), 5.02–
5.17 (m, 2 H, =CH2), 5.56–5.68 (m, 1 H, =CH), 7.29–7.42
(m, 8 H, ArH), 7.58–7.63 (m, 2 H, ArH). (Found C 63.3;
H 6.0%. C14 H16O5 requires C 63.3; H 6.06%).
1
2
3
4a
4b
4c
H
85
75
90
>98:2
>98:2
>98:2
C6H5
CH3
3h
3i
Both higher diastereoselectivities and shorter reaction
time for completion of reactions at pH 4.7 0.2 point to-
wards better participation of the carboxylate ion in the
chelation than the carboxylic acid moiety. The allylation
of imine derivatives of 2-oxocarboxylic acids to achieve
unnatural -amino acids is under investigation.
Acknowledgement
We thank CSIR New Delhi for financial assistance [01(1530)/98].
References
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(11) Similar increase in both rate of reaction and
diastereoselectivity of allylation at pH 4.0 and slowed
allylation at pH 7.0 was reported earlier (ref. 2d).
Synlett 2002, No. 4, 573–574 ISSN 0936-5214 © Thieme Stuttgart · New York