Convenient synthesis of t-butyl Z-3-substituted glycidates under conditions of phase-transfer catalysis

Article abstract of DOI:10.1016/S0040-4039(03)00234-X

Reactions of mixtures of t-butyl E- and Z-3-substituted glycidates 1a-h with 50% aq. sodium hydroxide and a catalyst, benzyltriethylammonium chloride, TEBAC in dichloromethane (phase-transfer catalysis, PTC) led to preferential hydrolysis of the E-isomers to afford pure (90-98%) t-butyl Z-3-substituted glycidates 1a-i in good yields; PTC cleavage of glycidates additionally substituted at C-2, 1g or C-3, 1h,i suggests that an aryl group in the Z isomers hampers attack of HO^- on the carbonyl carbon atom. As described in the literature, the diastereoselective PTC synthesis of Z-3-substituted glycidates and glycidonitriles consists of fast hydrolysis of E isomers present in mixtures with Z ones.

Full text of DOI:10.1016/S0040-4039(03)00234-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2359–2361
Convenient synthesis of t-butyl Z-3-substituted glycidates under
conditions of phase-transfer catalysis
Andrzej Jonczyk* and Tomasz Zomerfeld
Warsaw University of Technology, Faculty of Chemistry, Koszykowa 75, 00-662 Warsaw, Poland
Received 22 November 2002; revised 13 January 2003; accepted 24 January 2003
Abstract—Reactions of mixtures of t-butyl E- and Z-3-substituted glycidates 1a–h with 50% aq. sodium hydroxide and a catalyst,
benzyltriethylammonium chloride, TEBAC in dichloromethane (phase-transfer catalysis, PTC) led to preferential hydrolysis of the
E-isomers to afford pure (90–98%) t-butyl Z-3-substituted glycidates 1a–i in good yields; PTC cleavage of glycidates additionally
substituted at C-2, 1g or C-3, 1h,i suggests that an aryl group in the Z isomers hampers attack of HO− on the carbonyl carbon
atom. As described in the literature, the diastereoselective PTC synthesis of Z-3-substituted glycidates and glycidonitriles consists
of fast hydrolysis of E isomers present in mixtures with Z ones. © 2003 Elsevier Science Ltd. All rights reserved.
Esters of glycidic acid are usually prepared by base-pro-
moted reaction of esters of a-halogeno acids with car-
bonyl compounds (Darzens condensation).1 A variety
of base–solvent systems have been applied for this
purpose, including alkali metal hydroxides or carbon-
ates in the presence of a quaternary ammonium salt or
a crown ether as a catalyst2 (phase-transfer catalysis,
PTC3). Methyl or ethyl chloroacetate are cleaved by
alkali metal hydroxides; therefore, Darzens condensa-
tions with these esters are carried out in the presence of
powdered potassium carbonate and a phase-transfer
catalyst4 (solid–liquid variant of PTC). On the other
hand, Darzens condensations with t-butyl chloroacetate
can be performed with alkali metal hydroxides and a
PT catalyst.5 Irrespective of the PTC conditions, these
processes are usually restricted to aromatic aldehydes
and produce mixtures of Z- and E-3-arylglycidates.
Recently, diastereoselective Darzens condensations of
a-chloroesters, amides and nitriles with aromatic alde-
hydes, carried out in the presence of powdered potas-
sium hydroxide and tetrahexylammonium bromide
(THAB) as a catalyst in THF or diethyl ether, which
led to formation of Z-glycidic acid derivatives, have
been described.6 We wish to report that, in fact, this
process consists of the formation of mixtures of E and
Z isomers of the products, the first of which hydrolyses
at a relatively high rate.
When we carried out the condensation of t-butyl
chloroacetate with benzaldehyde in the presence of 50%
aq. sodium hydroxide and benzyltriethylammonium
chloride (TEBAC) as a catalyst in dichloromethane at
10–15°C for 1 h, the formation of white solid product
was noticed. This material was isolated and identified
(1H NMR, transformation into phenylacetaldehyde7) as
the slightly impure sodium salt of E-3-phenylglycidic
acid. The experiment described above indicates that
t-butyl 3-phenylglycidate 1a is prone to basic hydroly-
sis, to some extent. The organic products from the
reaction were conventionally worked-up and distilled to
afford t-butyl-3-phenylglycidate 1a, E/Z ca. 0.25 (yield
65%).
This observation prompted us to investigate hydrolysis
of a mixture of t-butyl E- and Z-3-phenylglycidate 1a
under PTC conditions. Stirring such a mixture (E/Z ca.
0.25) with 50% aq. sodium hydroxide and TEBAC as a
catalyst, in dichloromethane at 10–15°C, indicated that
the E isomer is cleaved at a much higher rate than the
Z isomer. After ca. 6 h, the crude mixture contained
]97% of the Z isomer which, after isolation and
distillation, was obtained in a yield of 84%8,9 (with
>0.5% of the E isomer and 2.5% of impurities deter-
mined by GC) (Table 1, entry 1). Without the catalyst,
not less than ca. 80% of ester 1a of practically the same
E/Z ratio was recovered. To determine the scope of this
reaction, mixtures of Z and E isomers of t-butyl glyci-
dates substituted at C-3 with aryl 1b–d, heteroaryl, 1e
or cyclohexyl, 1f groups were hydrolysed under the
same PTC conditions, to afford Z isomers 1b–f of high
purity and in good yield9 (Table 1, entries 2–6). Simi-
Keywords: phase transfer; hydrolysis; esters.
* Corresponding author. Tel.: +48-22-621-4230; fax: +48-22-628-2741;
e-mail: anjon@ch.pw.edu.pl
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00234-X

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A. Jonczyk, T. Zomerfeld / Tetrahedron Letters 44 (2003) 2359–2361
Table 1. Hydrolysis of glycidates 1a–j under conditions of PTC. Reagents and conditions: (i) 50% aq. NaOH, cat. TEBAC,
CH2Cl2, 10–15°C, 5–6 h
Entry
1
R1
R2
R3
E/Z in starting 1a
Z-1
Yield (%)
Purity (%)a
1b
2
3
4
5
6
7
8
9
a
b
c
d
e
f
g
h
i
Ph
H
H
H
H
H
H
H
Me
Ph
H
H
H
H
H
H
Me
H
H
0.25
0.40
0.21
0.32
2.95
0.93
0.56
0.40
–
84
78
75
66
70
68
86
60
50d
98
97
97
2-FC6H4
2-MeC6H4
4-ClC6H4
3-C4H3S
c-C6H11
Ph
98
90c
93c
95
Ph
Ph
95
92d
a Determined by GC.
b i-Propyl 3-phenylglycidate (1j, E/Z:0.69) gives after 0.5h Z-1a in yield of 51% (purity 95%).
c 5% of isomer E.
d Recovered ester 1g.
larly, mixtures of E- and Z-3-phenylglycidates substi-
tuted with a methyl group at C-2, 1g or C-3, 1h gave Z
isomers (Table 1, entries 7 and 8). In accordance with
expectation, the E isomer of i-propyl 3-phenylglycidate
1j was cleaved much faster than the analogous t-butyl
ester 1a (Table 1, entry 1). t-Butyl Z-3-arylglycidates
can be prepared by this two-step procedure in higher
yield than by previously described methodology.6
PTC systems (conc. aq. sodium hydroxide and a cata-
lyst, Aliquat 336) are not suitable for hydrolysis of
alkyl mesitoates while they are efficiently cleaved by
powdered potassium hydroxide with the same cata-
lyst.12 Thorough investigations indicate that PTC
hydrolysis of esters carried out in the presence of 50%
aq. sodium hydroxide depends on their structure, type
of solvent and catalyst used.13 Even t-butyl benzoate is
cleaved by means of 60% aq. potassium hydroxide
under conditions of triphase catalysis in high yield.14
When we repeated the reaction of t-butyl chloroacetate
with benzaldehyde under the conditions described,6,10
samples taken after 2 h and analysed by GC showed the
presence of both isomers of 1a (E/Z:0.41); the E
isomer was removed when a second portion of pow-
dered potassium hydroxide was added and the reaction
was carried out for 22 h.
Hydroxide anion associated with Q+ is inefficiently
transferred from water into an organic phase, particu-
larly when more lipophilic anions like Cl− or Br− are
present. This is the case in the reactions studied; chlo-
ride anion is introduced by the TEBAC catalyst. Fur-
thermore, phenylglycidate anions produced during the
reaction form ion pairs with Q+ which also seem to be
lipophilic. Thus, interfacial mechanisms of ester hydrol-
ysis cannot be discarded though results obtained with-
out the TEBAC catalyst are in favour of a reaction via
Q+OH− extracted into the organic phase.
Reaction of chloroacetonitrile with benzaldehyde car-
ried out under the same conditions,6,10 gave after 8 h a
mixture of E- and Z-3-phenylglycidonitrile (E/Z:
1.32), but after 100 h only the Z isomer was detected by
GC. So, the diastereoselective6 Darzens condensations
leading to esters and nitriles of Z glycidic acids are
actually based on selective hydrolysis of the E isomers
of E/Z mixtures.
Our investigations open the question as to why E
isomers of glycidates and glycidonitriles are more easily
hydrolysed than Z ones. The results described above, as
well as the rather slow rate of cleavage of 3,3-diphenyl
substituted glycidate 1i (Table 1, entry 9) suggest that
the aryl groups in Z isomers hampers attack by hydrox-
ide on the carbonyl carbon of the t-butoxycarbonyl or
the cyano group.15 Further work aimed at an explana-
tion of the experimental data is in progress.
The literature indicates that cleavage of esters carried
out in a two-phase system can be accelerated by a PT
catalyst. Thus dimethyl adipate hydrolyses exothermi-
cally in the presence of 50% aq. sodium hydroxide and
a Q+X− catalyst while no reaction occurs without the
catalyst. On the other hand, hydrolysis of methyl tetra-
decanoate is arrested after ca. 35% of reaction. In the
latter case, the Q+ ion associates with the long chain
carboxylate anion rather than with HO−, hampering
extraction of Q+OH− into the organic phase, and the
catalytic process is arrested.11 Typical liquid–liquid
Nevertheless, our paper reports a simple and efficient
method for preparation of t-butyl Z-3-arylglycidates
which are useful substrates in organic synthesis.16

A. Jonczyk, T. Zomerfeld / Tetrahedron Letters 44 (2003) 2359–2361
2361
References
27.42, 52.56, 55.05, 82.20, 114.46 (d, J=20.0), 120.78 (d,
J=13.4), 123.39 (d, J=3.5), 128.76 (d, J=3.5), 129.63 (d,
J=8.3), 161.00 (d, J=246), 165.37; anal. calcd for
C13H16O3F C, 65.55, H, 6.30; found C, 65.11, H, 6.39%;
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CH3), 3.77 (d, J=4.3, 1H, CHCO2But), 4.20 (d, J=4.3,
1H, CHPh), 7.0–7.5 (m, 4H, ArH); t-butyl Z-3-(4-
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58°C (MeOH); H NMR: 1.17 [s, 9H, C(CH3)3], 3.82 (d,
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ArCH), 7.11 (dd, J=5.0, J=1.2, 1H, ArH), 7.26 (dd,
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1
Z-3-cyclohexylglycidate 1f: bp 140°C/10 Torr; H NMR:
1.1–1.9 (m, 11H, c-hexyl), 1.45 [s, 9H, C(CH3)3], 2.79 (dd,
J=9.2, J=4.6, 1H, c-hexyl-CH), 3.37 (d, J=4.6, 1H,
CHCO2But); 13C NMR: 25.1, 27.9, 28.6, 30.4, 36.1, 53.1,
61.3, 82.1 167.3; t-butyl Z-2-methyl-3-phenylglycidate 1g:
bp 100–104°C/0.8 Torr; H NMR: 1.12 [s, 9H, C(CH3)3],
1.68 (s, 3H, CH3), 3.97 (s, 1H, CHPh), 7.2–7.4 (m, 5H,
ArH); t-butyl Z-3-methyl-3-phenylglycidate 1h: bp
1
1
130°C/0.6 Torr; H NMR: 1.11 [s, 9H, C(CH3)3], 1.71 (s,
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7. This reaction was carried out as described in Ref. 1 p. 428
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ArH); t-butyl 3,3-diphenylglycidate 1i: bp 140°C; mp
1
59–61°C (MeOH), H NMR: 1.20 [s, 9H, C(CH3)3], 3.88
for
conversion
of
3-phenylglycidic
acid
into
(s, 1H, CHCO2But), 7.3–7.5 (m, 10H, ArH); i-propyl
Z-3-phenylglycidate 1j, 1H NMR 0.98 [d, J=6.8, 3H,
CH(CH3)(CH3)], 0.99 [d, J=6.8, 3H, CH(CH3)(CH3)],
3.79 (d, J=4.6 Hz, 1H, HCPh), 4.25 (d, J=4.6 Hz, 1H,
HCCO2Pr-i), 4.85 [qq, 1H, J=6.8, J=6.8, CH(CH3)2],
7.2–7.5 (m, 5H, ArH).
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9. Procedure: t-butyl 3-phenylglycidates 1a, E/Z ca. 0.25
(1.15 g, 5.2 mmol), 50% aq. sodium hydroxide (4 mL),
TEBAC (0.05 g, 0.22 mmol) and CH2Cl2 (4 mL) were
vigorously stirred at 10–15°C for 6 h. The mixture was
diluted with water, the phases were separated, the aqueus
phase was extracted with CH2Cl2 (2×10 mL), the com-
bined organic extracts were washed with water, dried
(MgSO4), the solvent was evaporated, and the residue
was distilled in a Kugelrohr apparatus (bath temperature
120°C/0.6 Torr) to give t-butyl Z-3-phenylglycidate 1a
(0.75 g, yield 84%, based on the amount of Z isomer in
the substrate) of purity ]97% (GC). 1H NMR (400
MHz, CDCl3): l 7.41–7.26 (m, 5H, ArH), 4.22 (d, J=4.8
Hz, 1H, HCCO2Bu-t), 3.71 (d, J=4.8 Hz, 1H, HCPh),
1.17 (s, 9H, t-Bu). Characterisation data for compounds
10. Tetra-octylammonium bromide as a catalyst was used in
this reaction.
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15. Selective hydrolysis of the ethoxycarbonyl group in the E
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propanecarboxylate (NaOH, EtOH, H2O) has been
described. See: Kaiser, C.; Weinstock, J.; Olmstead, M. P.
Org. Synth. 1970, 50, 94–97.
16. Procedures for transfomation of E into Z glycidates, see:
(a) Adger, B. M.; Barkley, J. V.; Bergeron, S.; Cappi, M.
W.; Flowerdew, B. M.; Jackson, M. P.; McCague, R.;
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1
1b–g: H NMR spectra were measured at 400 MHz, 13C
NMR spectra at 100 MHz in CDCl3 solution, chemical
shifts (l) are given in ppm relative to TMS and coupling
constant (J) in Hz. All distillations were carried out in a
Kugelrohr apparatus. t-Butyl Z-3-(2-fluoro)phenyl-
1
glycidate 1b: bp 89–94°C/0.4 Torr; H NMR: 1.19 [s, 9H,
C(CH3)3], 3.69 (d, J=4.7, 1H, CHCO2But), 4.16 (d,
J=4.7, 1H, CHPh), 7.0–7.6 (m, 4H, ArH); 13C NMR: