Diastereoselective reduction of ketimines derived from (R)-3,4-dihydroxybutan-2-one: an alternative route to key intermediates for the synthesis of anticancer agent ES-285

Article abstract of DOI:10.1016/j.tetasy.2010.02.012

A simple and convenient procedure for the diastereoselective reduction of imines derived from (R)-3,4-dihydroxybutan-2-one is described. The use of sodium borohydride as a reducing agent in the reactions with pre-synthesised imines gave aminodiol derivatives with the appropriate stereochemistry for use as intermediates in the synthesis of anticancer agent ES-285. The aminodiols were isolated in ca. 62% yield.

Full text of DOI:10.1016/j.tetasy.2010.02.012

Tetrahedron: Asymmetry 21 (2010) 503–506
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Tetrahedron: Asymmetry
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Diastereoselective reduction of ketimines derived from (R)-3,4-dihydroxybutan-
2-one: an alternative route to key intermediates for the synthesis of anticancer
agent ES-285
*
*
Ana C. Allepuz, Ramón Badorrey, María D. Díaz-de-Villegas , José A. Gálvez
Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón, Instituto Universitario de Catálisis Homogénea, Universidad de
Zaragoza-CSIC, E-50009 Zaragoza, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and convenient procedure for the diastereoselective reduction of imines derived from (R)-3,4-
dihydroxybutan-2-one is described. The use of sodium borohydride as a reducing agent in the reactions
with pre-synthesised imines gave aminodiol derivatives with the appropriate stereochemistry for use as
intermediates in the synthesis of anticancer agent ES-285. The aminodiols were isolated in ca. 62% yield.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 2 February 2010
Accepted 16 February 2010
Available online 16 March 2010
1. Introduction
OR1
R1O
CH3
+
H2NR2
Chiral imines derived from conveniently protected D-glyceralde-
OR1
hyde have proven to be extremely versatile and readily available
starting materials for the synthesis of a variety of enantiomerically
pure chiral targets such as ABT derivatives, 1,4-dideoxy-1,4-imino-
hexitols, Selfotel or pipecolic acid-lysine and glutamic acid chimeras
among others.1 We recently described the preparation of 3-amino-
1,2-butanediol derivative 5, a key intermediate in the synthesis of
anticancer agent ES-285, by the addition of methyl organometallic
reagents to the N-benzylimine derived from (R)-2,3-O-isopropylid-
eneglyceraldehyde.2 The addition of an excess of methylmagnesium
bromide to this imine in the presence of BF3ꢀOEt2 gave the required
aminodiol derivative of (2S,3S)-configuration with high diastereose-
lectivity (96:4), which allowed the isolation of the product in 69%
yield. In contrast, the addition of an excess of methylmagnesium
bromide to the N-benzylimine derived from (R)-2,3-di-O-benzyl-
glyceraldehyde led to the corresponding aminodiol derivative with
total diastereoselectivity,3 although in this case the diastereoisomer
does not have the appropriate configuration for its use as an inter-
mediate in the synthesis of ES-285.
reducing
agent
O
R1O
CH3
or
NHR2
OR1
R1O
CH3
N
R2
Scheme 1. Alternative routes to (2S,3S)-3-amino-1,2-butanediol derivatives by
diastereoselective reduction of ketimines derived from (R)-3,4-dihydroxybutan-2-
one.
Herein we report our results on the asymmetric synthesis of
(2S,3S)-3-amino-1,2-butanediol derivatives starting from conve-
niently protected (R)-3,4-dihydroxybutan-2-one.
2. Results and discussion
A different approach to obtain 3-amino-1,2-butanediol deriva-
tives of (2S,3S)-configuration would involve the diastereoselective
addition of a hydride to imines derived from conveniently pro-
tected (R)-3,4-dihydroxybutan-2-one, a process that can be per-
formed by two alternative procedures; (a) reduction of imines
obtained in situ in reductive amination processes; and (b) hydride
reduction of pre-synthesised imines (Scheme 1).
The reaction of aldehydes or ketones with amines in the pres-
ence of reducing agents to give amines with more substituents,
usually known as reductive amination, is among the most useful
and important tools in the synthesis of amines.4,5 This approach
has been applied to the asymmetric synthesis of aminodiol
derivatives with variable results depending on the substrate and
reaction conditions.6
Among the different possibilities that exist, the use of metal
hydrides that selectively reduce imines in the presence of carbonyl
compounds is the method of choice. In this context, acid-stable
amine-boranes,7 sodium or lithium cyanoborohydrides8 or sodium
triacetoxyborohydride9 are the most commonly used reducing
* Corresponding authors. Tel.: +34 976762274; fax: +34 976761202 (M.D.D); tel.:
+34 976762273; fax: +34 976761202 (J.A.G.).
E-mail addresses: loladiaz@unizar.es (M.D. Díaz-de-Villegas), jagl@unizar.es (J.A.
Gálvez).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.02.012

504
A. C. Allepuz et al. / Tetrahedron: Asymmetry 21 (2010) 503–506
OR1
OR1
OR1
R1O
R1O
a
b
R1O
CH3
H
CH3
O
O
OH
3, R1-R1 = isopropylidene
1, R1-R1 = isopropylidene
1
1
4
2
, R = Bn
, R = Bn
Scheme 2. Synthesis of the starting ketones 3 and 4. Reagents and conditions: (a) CH3MgBr, Et2O, ꢁ20 °C; (b) n-Pr4NRuO4, NMO, CH2Cl2, rt (R1–R1 = isopropylidene 43% two
steps Ref.10, R1 = Bn 55% two steps).
reagents. We first examined the reductive amination of conve-
niently protected (R)-3,4-dihydroxybutan-2-one with benzylamine
using these reducing agents. (R)-3,4-Dihydroxybutan-2-ones 3 and
native to the synthesis of amines from ketones.14,15 This approach
was examined next and the results are summarised in Table 2.
The reduction of imine 7 with lithium triethyl borohydride in
THF at ꢁ20 °C for 24 h gave amine 5 as an 83/17 mixture of anti/
syn diastereoisomers in 45% yield (entry 1). The use of imine 8 as
the substrate under the same reaction conditions led to a signifi-
cant decrease in the yield (entry 4) and the by-products derived
from the elimination of the terminal benzyloxy moiety (Fig. 1)
were identified. The formation of such by-products has been ob-
served previously in the addition of certain nucleophiles to imines
derived from aldehyde 2.16
4 were obtained from the corresponding D-glyceraldehyde deriva-
tives 1 and 2 according to the procedure described by Leyes and
Poulter10 for the synthesis of ketone 3, with minor modifications
required when applied to ketone 4. The reaction of the D-glyceral-
dehyde derivatives 1 and 2 with methylmagnesium bromide fol-
lowed by oxidation of the resulting diastereomeric mixture of
glycerol derivatives with tetra-n-propylammonium perruthenate11
afforded ketones 3 and 4 in 43% and 55% yield, respectively
(Scheme 2).
The results of the reductive amination of (R)-3,4-dihydroxyb-
utan-2-ones 3 and 4 (Scheme 3) are summarised in Table 1. It
can be seen that various conditions failed to give the desired amin-
odiols in preparatively useful yields and/or with high diastereose-
OR1
OR1
reducing
agent
R1O
R1O
CH3
CH3
Bn
NHBn
N
OR1
OR1
1
1
1
1
7
8
5
6
, R1-R = isopropylidene
, R = Bn
, R1-R = isopropylidene
reducing
agent
R1O
R1O
CH3
, R = Bn
CH3
+
H2NBn
Scheme 4. Diastereoselective reduction of ketimines 7 and 8.
NHBn
O
3, R1-R1 = isopropylidene
5, R1-R1 = isopropylidene
A decrease in the reaction temperature improved the diastere-
oselectivity, which was total in the reduction of ketimine 8 at
ꢁ78 °C, but was detrimental in terms of amine yield; only 16% of
amine 6 of anti configuration was obtained (entry 5).
1
1
4
6
, R = Bn
, R = Bn
Scheme 3. Diastereoselective reductive amination of ketones 3 and 4.
Alkaline borohydrides were next tested as reducing agents. The
reduction of an ethanolic solution of imine 7 with sodium borohy-
dride at room temperature gave amine 5 as a 75/25 mixture of anti/
syn diastereoisomers in 90% yield (entry 6). The use of lithium or
potassium borohydride did not improve the diastereoselectivity
of the reduction process and was detrimental in terms of yield (en-
tries 7 and 8). The reaction yield and the level of diastereoselectiv-
ity in the reduction of ketimine 7 with sodium borohydride were
shown to be almost independent of the reaction temperature; a
change in the temperature from room temperature to ꢁ78 °C led
only to slight changes in the anti/syn ratio (compare entry 6 with
entries 9 and 10).
lectivities. The best results in the first screen were obtained in the
reductive amination of ketone 4 with benzylamine using sodium
triacetoxyborohydride/acetic acid (1 mmol) in 1,2-dichloroethane
(DCE) at room temperature (entry 6). Under these conditions the
corresponding amines12 were obtained in 46% yield and with a
74/26 diastereomeric ratio. A decrease in the reaction temperature
led to an increase in the diastereoselectivity of the reaction (entry
7), but below 0 °C this was accompanied by a decrease in the reac-
tion yield (entry 8).
The reduction of the preformed ketimines, obtained by the liter-
ature procedures,13 with metal hydrides is a useful synthetic alter-
Table 1
Diastereoselective reductive amination of ketones 3 and 4 according to Scheme 3
Entry
Ketone
Conditions
Molar ratio
Time (h)
Yieldc (%)
anti:synd
1
2
3
4
5
6
7
8
3
4
3
4
3
4
4
4
NaBH3CN, MeOH, rt
NaBH3CN, MeOH, rt
1/1.4a
22
40
6
28
24
52
46
22
43
46
32
53/47
50/50
54/46
58/42
81/19
74/26
81/19
79/21
1/1.4a
PicBH3, MeOH/HOAc (10:1), rt
PicBH3, MeOH/HOAc (10:1), rt
NaBH(OAc)3/HOAc, DCE, rt
NaBH(OAc)3/HOAc, DCE, rt
NaBH(OAc)3/HOAc, DCE, 0 °C
NaBH(OAc)3/HOAc, DCE, ꢁ20 °C
1/1a
1/1a
6
1/1.4/1b
1/1.4/1b
1/1.4/1b
1/1.4/1b
48
24
30
96
a
b
c
Moles of substrate/moles of reducing agent.
Moles of substrate/moles of reducing agent/moles of acetic acid.
Mixture of diastereoisomers. Determined by 1H NMR from crude reaction mixtures using 1,3,5-trimethoxybenzene as an internal standard.
d
Determined by 1H NMR in CDCl3 (5) or C6D6 (6) from crude reaction mixtures.

A. C. Allepuz et al. / Tetrahedron: Asymmetry 21 (2010) 503–506
505
Table 2
Diastereoselective reduction of ketimines 7 and 8 according to Scheme 4
Entry
Ketimine
Conditions
Molar ratioa
Time (h)
Yieldb (%)
anti:sync
1
2
3
4
5
6
7
8
7
7
7
8
8
7
7
7
7
7
8
8
8
LiEt3BH, THF, ꢁ20 °C
LiEt3BH, THF, ꢁ40 °C
LiEt3BH, THF, ꢁ78 °C
LiEt3BH, THF, ꢁ20 °C
LiEt3BH, THF, ꢁ78 °C
NaBH4, EtOH, rt
LiBH4, EtOH, rt
KBH4, EtOH, rt
NaBH4, EtOH, ꢁ20 °C
NaBH4, EtOH, ꢁ78 °C
NaBH4, EtOH, rt
1/1.5
1/1.5
1/1.5
1/1.5
1/3
1/2
1/2
1/2
1/2
24
30
72
48
84
1.5
1.5
1.5
1.5
1.5
1
45
38
25
38
16
90
51
79
91
90
50
60
72
83/17
88/12
91/9
91/9
>98/2
75/25
74/26
74/26
74/26
72/28
76/24
79/21
85/15
9
10
11
12
13
1/2
1/1.2
1/1.2
1/1.2
NaBH4, EtOH, ꢁ20 °C
2
2
NaBH4, EtOH, ꢁ78 °C
a
b
c
Moles of substrate/moles of reducing agent.
Mixture of diastereoisomers. Determined by 1H NMR on crude reaction mixtures using 1,3,5-trimethoxybenzene as an internal standard.
Determined by 1H NMR in CDCl3 (5) or C6D6 (6) from crude reaction mixtures.
OBn
O
OBn
O
1,2-O-isopropylidene-
D
-glyceraldehyde with methylmagnesium
bromide followed by oxidation of the resulting diastereomeric mix-
ture of glycerol derivatives, as previously described in the litera-
CH3
CH3
ture.10
(S)-N-(1-(2,2-Dimethyl-1,3-dioxolan-4-yl)ethylidene)-1-
phenylmethanamine 7 was prepared from (R)-2,2-dimethyl-1,3-
dioxolan-4-yl methyl ketone according to a literature procedure.13
FT-IR spectra of oils were recorded as thin films on NaCl plates
and FT-IR spectra of solids were recorded as KBr pellets, using a
Thermo Nicolet Avatar 360 FT-IR spectrophotometer; mmax values
expressed in cmꢁ1 are given for the main absorption bands. Optical
rotations were measured on a Jasco P-1020 polarimeter at k
by-product A
by-product B
Figure 1. By-products identified in the reduction of imine 8 with lithium triethyl
borohydride.
The reduction of imine 8 with sodium borohydride at room
temperature led to a 76/24 mixture of anti/syn diastereoisomers
of amine 6 but only 50% yield was obtained (entry 11). In this case
a decrease in the reaction temperature increased both the diaste-
reoselection and the reaction yield (compare entry 11 with entries
12 and 13). Working at ꢁ78 °C amine 6 with the (2S,3S)-configura-
tion could be isolated in 61% yield.
589 nm and 25 °C in a cell with 10 cm path length, [a] values
D
are given in 10ꢁ1 deg cm2 gꢁ1 and concentrations are given in g/
100 mL. 1H NMR and 13C NMR spectra were acquired on a Bruker
AV-400 instrument operating at 400 MHz for 1H NMR and
100 MHz for 13C NMR using a 5-mm probe. The chemical shifts
(d) are reported in parts per million and are referenced to the resid-
ual solvent peak. Coupling constants (J) are quoted in Hertz. The
following abbreviations are used: s, singlet; d, doublet; m, multi-
plet; dd, doublet of doublets; qd, quartet of doublets, br s, broad
signal. High resolution mass spectra were recorded using a Bruker
Daltonics MicroToF-Q instrument from methanolic solutions using
the positive electrospray ionisation mode (ESI+).
3. Conclusion
It can be concluded from this study that the best way to obtain
(2S,3S)-3-amino-1,2-butanediol derivatives from imines derived
from (R)-3,4-dihydroxybutan-2-one is to perform the metal hy-
dride reduction of pre-synthesised imines using sodium borohy-
dride as the reducing agent. Reduction of imines 7 or 8 under the
appropriate reaction conditions allowed the isolation of aminodiol
derivatives 5 or 6 with the required anti configuration in 64% or
61% yield, respectively. This constitutes as a new approach to the
asymmetric synthesis of the useful intermediates for the antican-
cer agent ES-285.
4.2. (R)-3,4-Bis(benzyloxy)butan-2-one 4
A
solution of (R)-2,3-di-O-benzylglyceraldehyde (3.98 g,
14.7 mmol) in dry diethyl ether (15 mL) was added under argon
to a cooled (ꢁ20 °C) 3 M ethereal solution of methylmagnesium
bromide (14.8 mL, 44.3 mmol) in dry diethyl ether (150 mL). The
cooling bath was removed and the mixture was stirred for 12 h
at room temperature. The reaction mixture was treated with satu-
rated aqueous NH4Cl (15 mL) and the aqueous layer was extracted
with diethyl ether (3 ꢂ 20 mL). The combined organic layers were
dried over anhydrous MgSO4, filtered and evaporated in vacuo to
afford a diastereomeric mixture of alcohols, which was used in
the next step without further purification.
4. Experimental
4.1. General experimental
All the reagents for the reactions were of analytical grade and
were used as obtained from commercial sources. All manipulations
with air-sensitive reagents were carried out under a dry argon atmo-
sphere using standard Schlenk techniques. Anhydrous solvents
were used with the exception of methanol. Wherever possible the
reactions were monitored by TLC. TLC was performed on precoated
silica gel polyester plates and the products were visualised using UV
light (254 nm) and ninhydrin or phosphomolybdic acid as visualis-
ing agents followed by heating. Column chromatography was
A
solution of N-methylmorpholine oxide (NMO) (9.1 g,
77.7 mmol) in dichloromethane (100 mL) was treated with MgSO4
(6.0 g, 49.9 mmol) and the mixture was stirred for 20 min at room
temperature. The drying agent was removed by filtration and 4 Å
molecular sieves and a solution of the obtained diastereomeric
mixture of alcohols (3.7 g, 12.94 mmol) in dichloromethane
(20 mL) were added. The solution was stirred for 10 min and tet-
ra-n-propylammonium perruthenate (149 mg, 0.42 mmol) was
added. The mixture was stirred for 1 h at room temperature, fil-
performed using silica gel (60 Å, 35–70
dioxolan-4-yl methyl ketone 3 was prepared by the reaction of
lm). (R)-2,2-Dimethyl-1,3-

506
A. C. Allepuz et al. / Tetrahedron: Asymmetry 21 (2010) 503–506
tered through CeliteÒ and evaporated in vacuo. Purification of the
crude product by silica gel column chromatography (eluent:
EtOAc/hexanes 1:8) afforded 2.21 g (55%) of compound 4 as a pale
pure compound 6 of anti configuration as a colourless oil.
½
a 2D5
ꢃ
¼ ꢁ3:5 (c 0.70, CHCl3); IR (neat, cmꢁ1): mmax 3330, 1069; 1H
NMR (400 MHz, CDCl3) d 1.00 (d, J = 6.4 Hz, 3H), 1.63 (br s, 1H),
2.98–2.90 (m, 1H), 3.58 (d, J = 13.2 Hz, 1H), 3.50–3.65 (m, 3H),
3.71 (d, J = 13.2 Hz, 1H), 4.43 (d, J = 12.4 Hz, 1H), 4.47 (d,
J = 12.4 Hz, 1H), 4.50 (d, J = 12.0 Hz, 1H), 4.64 (d, J = 12.0 Hz, 1H),
yellow oil. ½a 2D5
ꢃ
¼ þ32:2 (c 0.91, CHCl3); IR (neat, cmꢁ1):
mmax 1716,
1105; 1H NMR (400 MHz, CDCl3) d 2.23 (s, 3H), 3.75 (d, J = 4.0 Hz,
2H), 3.98 (dd, J = 4.0, 4.0 Hz, 1H), 4.52 (d, J = 12.4 Hz, 1H), 4.56 (d,
J = 12.4 Hz, 1H), 4.59 (d, J = 12.0 Hz, 1H), 4.67 (d, J = 12.0 Hz, 1H),
7.16–7.27 (m, 10H); 13C NMR (100 MHz, CDCl3) d 27.1, 70.1, 72.5,
73.4, 83.9, 127.6, 127.6, 127.8, 127.9, 128.3, 128.4, 137.3, 137.6,
209.2.; HRMS (ESI+): m/z [M+Na+] calcd for C18H20NaO3 (MNa+)
307.1305, found 307.1318.
7.10–7.40 (m, 15H); 1H NMR (400 MHz, C6D6)
d 1.00 (d,
J = 6.4 Hz, 3H), 2.87 (qd, J = 6.4, 3.6 Hz, 1H), 3.56 (d, J = 13.2 Hz,
1H), 3.56 (dd, J = 9.2, 3.2 Hz, 1H), 3.67 (d, J = 13.2 Hz, 1H), 3.60–
3.70 (m, 2H), 4.30 (d, J = 12.0 Hz, 1H), 4.34 (d, J = 12.0 Hz, 1H),
4.54 (d, J = 12.0 Hz, 1H), 4.72 (d, J = 12.0 Hz, 1H), 7.05–7.40 (m,
15H); 13C NMR (100 MHz, CDCl3) d 15.9, 51.5, 53.2, 71.1, 72.5,
73.3, 80.8, 126.7, 127.4, 127.5, 127.5, 127.7, 128.0, 128.2, 138.3,
138.8, 140.6.; HRMS (ESI+): m/z [M+H+] calcd for C25H30NO2
(MH+) 376.2271, found 376.2281.
4.3. (S)-N-[3,4-Bis(benzyloxy)butan-2-ylidene]-1-phenylmethan-
amine 8
Benzylamine (0.62 mL, 5.1 mmol) and triethylamine (1.2 mL,
8.45 mmol) were successively added dropwise to a solution of ke-
tone 4 (1.2 g, 4.2 mmol) in dry dichoromethane (10 mL) under ar-
gon at room temperature. The solution was cooled to ꢁ78 °C and a
1 M solution of titanium tetrachloride in dichloromethane (2.1 mL,
2.1 mmol) was carefully added dropwise, while maintaining the
temperature below ꢁ78 °C. The resulting suspension was warmed
to room temperature and stirred for 5 h. The reaction mixture was
treated with ice-cold water (15 mL) and filtered through CeliteÒ.
The filtrate was cooled to 0 °C and treated with cooled (0 °C) 1 M
aqueous NH4Cl (15 mL). The organic layer was washed with ice-
cold water (15 mL), dried over anhydrous MgSO4, filtered and
evaporated in vacuo to afford ketimine 8, which was used in the
next step without further purification. 1H NMR (400 MHz, CDCl3)
d 1.89 (s, 3H), 3.69 (dd, J = 10.5, 5.4 Hz, 1H), 3.73 (dd, J = 10.5,
6.0 Hz, 1H), 4.23 (dd, J = 6.0, 5.4 Hz, 1H), 4.45–4.62 (m, 6H), 7.10–
7.40 (m, 15H).
Acknowledgements
The financial support of the Spanish Ministry of Science and
Innovation and European Regional Development Fund (CTQ2008-
00187/BQU) and the Government of Aragón (GA E-71) is
acknowledged.
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To a solution of ketimine 7 (233 mg, 1.0 mmol) in ethanol
(10 mL) at ꢁ78 °C under argon was added sodium borohydride
(75.6 mg, 2.0 mmol) and stirring was continued for 1.5 h at the
same temperature. The solvent was removed by evaporation in va-
cuo and water (3 mL) was added to a solution of the resulting res-
idue in diethyl ether (10 mL). The mixture was treated with
saturated aqueous NH4Cl (15 mL) and extracted with diethyl ether
(3 ꢂ 15 mL). The combined organic layers were dried over anhy-
drous MgSO4, filtered and concentrated to give 5 as a 75/25 anti/
syn mixture of diastereoisomers. Purification of the crude product
by silica gel column chromatography (first eluent: diethyl ether/
hexanes 1:1, second eluent: diethyl ether/hexanes 3:1) afforded
151 mg (64%) of pure compound 5 of anti configuration, the phys-
ical and spectroscopic data for which fully agree with those previ-
ously described.2
ˇ
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4.5. (2S,3S)-N-Benzyl-3,4-bis(benzyloxy)butan-2-amine 6
12. Aminodiol derivatives
5 with an anti-configuration and 6 with a syn-
configuration are known compounds and were identified by comparison of
their spectroscopic and physical data with those of authentic samples (see
Refs. 2,3).
To a solution of ketimine 8 (373 mg, 1.17 mmol) in ethanol
(10 mL) at ꢁ78 °C under argon was added sodium borohydride
(45.4 mg, 1.2 mmol) and stirring was continued for 2 h at the same
temperature. The solvent was removed by evaporation in vacuo
and water (3 mL) was added to a solution of the resulting residue
in diethyl ether (10 mL). The mixture was acidified with 2 M
hydrochloric acid, neutralised with saturated aqueous NaHCO3
and extracted with diethyl ether (3 ꢂ 15 mL). The combined organ-
ic layers were dried over anhydrous MgSO4, filtered and concen-
trated to give 6 as an 85/15 anti/syn mixture of diastereoisomers.
Purification of the crude product by silica gel column chromatogra-
phy (eluent: diethyl ether/hexanes 1:3) afforded 229 mg (61%) of
13. Palomo, C.; Aizpurua, J. M.; García, J. M.; Galarza, R.; Legido, M.; Urchegui, R.;
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2079.
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Synthesis; Trost, B. N., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 8,
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16. See for example: (a) Badorrey, R.; Cativiela, C.; Díaz-de-Villegas, M. D.; Díez, R.;
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Díaz-de-Villegas, M. D.; Gálvez, J. A. Tetrahedron Lett. 2003, 44, 9189–9192.