Preparation of Nd/Na heterogeneous catalyst from bench-stable and inexpensive Nd salt for an anti-selective catalytic asymmetric nitroaldol reaction

Article abstract of DOI:10.1016/j.tetlet.2016.03.041

A Nd/Na heterobimetallic complex prepared from an amide-based chiral ligand, Nd alkoxide, and NaHMDS is a highly efficient heterogeneous catalyst for an anti-selective catalytic asymmetric nitroaldol reaction. Nd alkoxide is sensitive to moisture, expensi

Full text of DOI:10.1016/j.tetlet.2016.03.041

Tetrahedron Letters 57 (2016) 1815–1819
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Preparation of Nd/Na heterogeneous catalyst from bench-stable
and inexpensive Nd salt for an anti-selective catalytic asymmetric
nitroaldol reaction
⇑
⇑
Akihito Nonoyama, Kazuki Hashimoto, Akira Saito, Naoya Kumagai , Masakatsu Shibasaki
Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A Nd/Na heterobimetallic complex prepared from an amide-based chiral ligand, Nd alkoxide, and
NaHMDS is a highly efficient heterogeneous catalyst for an anti-selective catalytic asymmetric nitroaldol
reaction. Nd alkoxide is sensitive to moisture, expensive, and scarce, making it difficult to use the Nd/Na
catalyst in large-scale applications. Herein we describe a new protocol that allows for catalyst prepara-
tion from bench-stable and inexpensive NdCl3Á6H2O with comparable catalytic activity.
Ó 2016 Elsevier Ltd. All rights reserved.
Received 13 February 2016
Revised 9 March 2016
Accepted 12 March 2016
Available online 15 March 2016
Keywords:
Nitroaldol
Neodymium
Bimetallic complex
Flow reaction
Enantioselective
The nitroaldol (Henry) reaction, a carbon–carbon bond-forming
reaction of nitroalkanes and carbonyl compounds (typically alde-
hydes), offers expeditious access to vicinal amino alcohols after
reducing the nitro group.1,2 Given the ready availability of these
substrates and the established synthetic utility of vicinal amino
alcohols, particularly for medicinal chemistry,3 the nitroaldol reac-
tion is one of the most widely used C–C bond-forming reactions in
the organic reaction toolbox (Scheme 1). Since our first report ren-
dering this reaction in a catalytic and asymmetric manner with
syn-diastereoselectivity,4 major challenges in this field have been
simultaneous control of the diastereo- and enantioselectivity,
allowing for stereoselective access to one of the four vicinal
nitroalkanols.5 Shortly after Ooi’s report on the catalytic anti-selec-
tive and enantioselective nitroaldol reaction,6 we disclosed an Nd/
Na heterobimetallic complex as an effective heterogeneous cata-
lyst for producing anti-nitroaldol products with a broad substrate
scope (Scheme 2).7,8 The Nd/Na catalyst was readily prepared using
an amide-based ligand 1, NdO1/5(OiPr)13/5, and NaHMDS in THF/
EtNO2; self-assembly of 1/Nd/Na proceeded with incorporation of
EtNO2 to give the powdered heterogeneous catalyst.7b,9 Catalyst
preparation in the presence of multi-walled carbon nanotubes
(MWNT) allowed for self-assembly in the fibrous matrix of the
Scheme 1. Overview of nitroaldol (Henry) reaction.
Scheme 2. Overview of the previously developed Nd/Na heterobimetallic hetero-
geneous catalyst for anti-selective nitroaldol reaction.
smaller catalyst clusters that enabled higher catalytic efficiency,
catalyst reuse, and reactions in a continuous-flow platform.10
An inherent problem, however, remained unsolved—the insta-
bility and limited availability of NdO1/5(OiPr)13/5. This Nd alkoxide
is (1) expensive;11 (2) unstable to moisture; (3) and requires
MWNT, thereby affording
a MWNT-confined catalyst with
⇑
Corresponding authors.
E-mail addresses: nkumagai@bikaken.or.jp (N. Kumagai), mshibasa@bikaken.or.
jp (M. Shibasaki).
http://dx.doi.org/10.1016/j.tetlet.2016.03.041
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.

1816
A. Nonoyama et al. / Tetrahedron Letters 57 (2016) 1815–1819
Table 1
Screening of Nd saltsa
A
For entries 1–3
1
Nd salt
3 mol%
in THF
ligand
NaHMDS
6 mol%
30 mM
rt
3 mol%
300 mol%
EtNO2 centrifuge
3
precipitate + supernatant
B For entries 4–9
self-
Nd salt NaHMDS ligand 1 NaHMDS
assembly
3 mol%
in THF
9 mol%
3 mol%
6 mol%
60 °C
30 mM
rt
12 h
OH
O
precipitate
Ph
+
THF, –40 °C, 20 h
Ph
H
NO2
NO2
2a
3
4a
Entry
Nd salt
Ambient conditions
€/g-Ndb
Prepn
Yieldc (%)
anti/synd
eee (%)
1f
2
3
4
5
6
7
8
9
NdO1/5(OiPr)13/5
Nd(HMDS)3
Nd(OH)3
Nd(NO3)3Á6H2O
Nd(OAc)3ÁH2O
NdF3
À
À
+
+
+
+
+
+
+
239
240
17
3.3
1.8
0.9
11
A
A
A
B
B
B
B
B
B
99
>99
<5
<5
<5
<5
99
<5
42
>20/1
>20/1
1.7/1
2.7/1
1.7/1
1.2/1
>20/1
1.9/1
6.8/1
92
94
ndg
ndg
ndg
ndg
93
NdCl3
NdCl3Á6H2O
1.6
40
ndg
33
NdBr3
a
b
c
d
e
f
2a: 0.4 mmol, 3: 4.0 mmol.
Cited references are described in ESI.
Determined by 1H NMR analysis of the crude mixture with DMF as an internal standard.
Determined by 1H NMR analysis of the crude mixture.
Ee of anti diastereomer. Determined by chiral stationary-phase HPLC analysis.
Data from Ref. 7b. Nd salt in THF was mixed into ligand 1/THF.
nd: not determined.
g
Table 2
Screening of Na saltsa
A
For entries 1–3,5–8
y [mM]
z [°C]
1
Nd salt
3 mol%
in THF
ligand
Na salt
x
3 mol%
mol%
300 mol%
EtNO2 centrifuge
3
precipitate + supernatant
B For entry 4
self-
Nd salt
3 mol%
in THF
Na salt
x mol%
ligand 1
assembly
3 mol%
y
z
[mM]
[°C]
OH
O
precipitate
THF, –40 °C, 20 h
Ph
+
Ph
H
NO2
NO2
4a
2a
3
Entry
Nd salt
Na salt
€/g-Ndb
€/g-Nab
Prepn
Yieldc (%)
anti/synd
eee (%)
x
y
z
1
2
3
4
5
6
7
8f
NdCl3
NaHMDS
18
18
18
18
12
18
18
18
11
35
35
A
A
A
B
A
A
A
A
30
30
40
40
40
40
40
40
rt
rt
93
97
98
<5
40
98
>99
97
>20/1
>20/1
>20/1
5.2/1
>20/1
>20/1
>20/1
>20/1
93
95
93
ndg
95
94
93
93
NdCl3Á6H2O
NdCl3Á6H2O
NdCl3Á6H2O
NdCl3Á6H2O
NdCl3Á6H2O
NdCl3Á6H2O
NdCl3Á6H2O
NaHMDS
NaOtBu
NaOtBu
NaOtBu
NaOtAm
NaOEt
1.6
1.6
1.6
1.6
1.6
1.6
1.6
0.6
0.6
0.6
2.7
0.3
0.6
60
60
60
60
60
60
NaOtBu
a
b
c
d
e
f
2a: 0.4 mmol, 3: 4.0 mmol.
Cited references are described in ESI.
Determined by 1H NMR analysis of the crude mixture with DMF as an internal standard.
Determined by 1H NMR analysis of the crude mixture.
Ee of anti diastereomer. Determined by chiral stationary-phase HPLC analysis.
18 mg of MWNT was added before adding EtNO2 (3a).
nd: not determined.
g

A. Nonoyama et al. / Tetrahedron Letters 57 (2016) 1815–1819
1817
alternative that produced a similar reaction outcome as NdO1/5(Oi-
Pr)13/5 in the nitroaldol reaction of benzaldehyde (2a) and EtNO2
(3). The cost and instability, however, remained comparable, and
thus further modifications were needed (Table 1, procedure A,
entries 1, 2). We searched for bench-stable and neutral Nd salts
to prepare the catalyst with a greater amount of NaHMDS to com-
pensate for the basicity and facilitate self-assembly. Because
potentially basic Nd(OH)3 was ineffective for catalyst preparation,
likely due to insolubility in THF (entry 3), in situ preparation of Nd
(HMDS)3 from various readily available and inexpensive Nd salts
was examined with a 3-fold excess of NaHMDS (Table 1, procedure
B).12 The highly cost-effective Nd salts, e.g., Nd(OAc)3ÁH2O, Nd
(NO3)3Á6H2O, and NdF3, barely afforded the catalysts sufficiently
active to promote the nitroaldol reaction (entries 4–6). In contrast
to NdF3, the catalyst prepared from NdCl3 produced a nearly simi-
lar reaction outcome to that obtained using NdO1/5(OiPr)13/5 (entry
1 vs entry 7). NdBr3 delivered less effective catalyst to afford pro-
duct 4a with an inferior yield and stereoselectivity (entry 9).
Although the hydrate form of NdCl3 was much less expensive,
the use of NdCl3Á6H2O in the identical catalyst preparation proce-
dure afforded only trace amounts of product 4a (entry 8).
Scheme 3. Schematic representation of new preparation protocol of the Nd/Na
heterogeneous catalyst. The solid white object is a magnetic stirring bar.
handling in a glove box under an inert atmosphere, which hampers
widespread use of this particularly useful catalyst. Herein we
report a new catalyst preparation procedure using an alternative
bench-stable and inexpensive NdCl3Á6H2O as the Nd salt. The pre-
viously required NaHMDS as a Na source was also replaced with
more common and less expensive Na alkoxides. The newly formed
catalyst was characterized by XRD and STEM, and exhibited cat-
alytic activity comparable to that of NdO1/5(OiPr)13/5
.
We selected NdO1/5(OiPr)13/5 as the Nd salt of choice due to its
high solubility in the preferred reaction solvent, e.g., THF, and its
basic character was also suitable for self-assembly with phenolic
ligand 1. Based on these criteria, Nd(HMDS)3 was an appropriate
Figure 1. STEM image of MWNT-confined catalyst prepared by new protocol (NdCl3Á6H2O/NaOtBu). (a) STEM image; (b) merged image of STEM and EDS mapping for Nd, F,
and Cl; (c) EDS mapping analysis for Nd detection; (d) EDS mapping analysis for F detection; (e) EDS mapping analysis for Cl detection.

1818
A. Nonoyama et al. / Tetrahedron Letters 57 (2016) 1815–1819
Given the lower cost of NdCl3 (11 euro/1 g-Nd) compared with
The Nd/Na heterobimetallic heterogeneous catalysts prepared
by the original (NdO1/5(OiPr)13/5/NaHMDS)7b and new
(NdCl3Á6H2O/NaOtBu) protocol were analyzed by powder XRD
analysis.16 As expected based on the comparable reaction out-
comes in the nitroaldol reaction, we observed nearly identical
diffraction patterns. Several unique peaks observed for the new
catalyst were assigned as peaks derived from NaCl. STEM and
EDS mapping images of the MWNT-confined catalyst confirmed
that the catalyst clusters were trapped in the fibrous network of
the MWNT (Fig. 1); characteristic X-ray areas of fluorine (derived
from ligand 1), chlorine, and Nd were superimposed with the cat-
alyst image. Chloride anions derived from NdCl3Á6H2O, which is
absent in the original method, located uniformly in the catalyst
and had no negative effect on the catalyst activity.
NdO1/5(OiPr)13/5 (239 euro/1 g-Nd),11 we directed our attention to
establishing a reliable and cost-effective protocol based on its
hydrate form, NdCl3Á6H2O (1.6 euro/1 g-Nd) (Table 2).11 Pre-incu-
bation of NdCl3 and 3-fold excess of NaHMDS could be omitted
for operational simplicity; mixing 6-fold excess of NaHMDS with
NdCl3/ligand 1 in THF gave a similar result (Table 1, entry 7 vs
Table 2, procedure A, entry 1). This simplified procedure was valid
for NdCl3Á6H2O, presumably due to the presence of ligand 1 upon
contact with Nd and Na salts, which reduced the negative effect
of the hydrates (entry 2). NaHMDS (35 euro/1 g-Na) was also
replaced with less expensive and more readily available NaOtBu
(0.6 euro/1 g-Na) under more concentrated conditions (40 mM in
ligand 1) at a higher temperature (60 °C),11 affording the nitroaldol
product 4a without any detrimental effects on the reaction out-
come (entry 3).13
The Nd/Na catalyst prepared via the new protocol was evalu-
ated using various substrates in comparison with the catalyst pre-
pared via the original protocol (Table 3). The results of the original
catalyst using the same catalyst loading (based on Nd) are shown
in parentheses,7b and almost identical reaction outcomes were
Formation of the Nd/Na heterogeneous catalyst under these
conditions is delineated in Scheme 3.14 Unexpectedly, pre-incuba-
tion of NdCl3Á6H2O and NaOtBu in the absence of ligand 1 under
otherwise identical conditions gave a solid material with almost
no catalytic activity (procedure B, entry 4), presumably because
NdCl3Á6H2O and NaOtBu produced an insoluble aggregate and
therefore no productive complexation with 1 proceeded. The
amount of base was also important; reducing NaOtBu to 4-fold
excess reduced the catalytic efficiency (entry 5).15 Other Na alkox-
ides under otherwise identical conditions produced similar reac-
tion outcomes (entries 6, 7). Under the optimized conditions for
catalyst preparation, mixing the MWNT before adding EtNO2 pro-
duced MWNT-confined catalyst for potential use in a flow reaction
(vide infra). The MWNT-confined catalyst had increased durability,
was easily filtered for recovery, and produced similar reaction out-
come in a batch system (entry 8). Replacing the Nd and Na salts
from NdO1/5(OiPr)13/5/NaHMDS to NdCl3Á6H2O/NaOtBu resulted in
a ca. 120-fold cost reduction.
obtained for
a series of aldehydes (entries 1–10). ortho-
Substituent, electron-donating and -withdrawing substituents at
para position were tolerated to afford the nitroaldol products in
high yields, anti-selectivity, and enantioselectivity (entries 2–5),
albeit with
nitrobenzaldehyde (2f) (entry 6). Although the reaction with
cinnamaldehyde (2g) as an archetypal ,b-unsaturated aldehyde
a
little erosion in stereoselectivity for 4-
a
afforded reasonable yields and stereoselectivity without forming
a 1,4-adduct (entry 7), lower diastereoselectivity was generally
observed for aliphatic aldehydes (entries 8–10).
A branched
aldehyde, e.g., cyclohexanecarboxaldehyde (2h) exhibited better
stereoselectivity (entry 8) and self-condensation of aliphatic
aldehydes was barely detected (entries 8–10).
The MWNT-confined Nd/Na heterobimetallic catalyst prepared
via the new protocol was applied to a continuous-flow reaction
(Scheme 4).17 The MWNT-confined catalyst was suspended in
THF with dried Celite and packed in a stainless steel column with
end-capping disk frits (2 lm) (62.2 lmol based on Nd). Benzalde-
Table 3
hyde (2a) (0.1 M/THF) and EtNO2 (3) (1.0 M/THF) were introduced
in separate streams at 4.2 mL/h using syringe pumps and 2a was
passed through an MS3A column and a NaHCO3 column to remove
trace amounts of water and acidic impurities. The two streams
merged in a mixer and the resulting substrate mixture was pre-
cooled to À40 °C before entering the catalyst column. The flow sys-
tem was operated for 24 h with high conversion and
stereoselectivity to afford 1.63 g of product 4a (90% yield, anti/
syn = 20/1, 90% ee, TON = 145). The flow system is advantageous
because (1) the heterogeneous catalyst was prepared by simple
Substrate generality of the nitroaldol reaction promoted by the Nd/Na heterobimetal-
lic catalyst via new protocol (NdCl3Á6H2O/NaOtBu)a
NdCl3•6H2O 3 mol%
1
ligand
3 mol%
NaOtBu
18 mol%
3
EtNO2 ( ) 300 mol%
precipitate
OH
O
R1
+
THF, –40 °C, 20 h
R1
H
NO2
NO2
2
3
4
Entry
Aldehyde 2
4
Yieldb,c (%)
anti/synb,d
eeb,e (%)
R1=
Ph
1
2
3
2a
2b
2c
2d
2e
2f
2g
2h
2i
4a
4b
4c
4d
4e
4f
4g
4h
4i
96 (99)
95 (99)
87 (89)
91 (88)
92 (99)
92 (99)
95 (96)
90 (92)
94 (99)
90 (93)
>20/1 (>20/1)
>20/1 (>20/1)
>20/1 (>20/1)
19/1 (15/1)
>20/1 (>20/1)
6.5/1 (5.7/1)
>20/1 (>20/1)
6.8/1 (8.3/1)
4.4/1 (4.9/1)
3.3/1 (3.4/1)
93 (92)
99 (98)
99 (97)
97 (94)
96 (96)
88 (86)
98 (97)
94 (95)
82 (77)
85 (87)
2,4-Me2C6H3
4-BnOC6H4
4-NCC6H4
4-MeO2CC6H4
4-NO2C6H4
(E)-PhCH@CH
cHex
4
5f
6
7
8g,h
9g
10g
PhCH2CH2
nC8H17
2j
4j
a
2a: 0.4 mmol, 3a: 4.0 mmol.
Data in parentheses are obtained from the catalyst prepared from the original
b
protocol (NdO1/5(OiPr)13/5/NaHMDS).7b
c
Isolated yield of diastereomixture.
d
Determined by 1H NMR analysis of the crude mixture.
e
Ee of anti diastereomer. Determined by chiral stationary-phase HPLC analysis.
Run for 14 h.
DME was used as solvent with 6 mol% of catalyst.
Run for 22 h.
f
g
Scheme 4. Nitroaldol reaction in a continuous-flow platform with MWNT-confined
Nd/Na heterogeneous catalyst prepared via new protocol.
h

A. Nonoyama et al. / Tetrahedron Letters 57 (2016) 1815–1819
1819
mixing without any covalent linkage;18 (2) no work-up procedure
was required and evaporation of the eluent gave the crude pro-
duct; (3) the cooling volume was significantly reduced to decrease
the electric power required for cryogenic conditions. The nitro pro-
duct of 4a can be readily reduced to give (À)-norephedrine.8e
In conclusion, we established a new preparation protocol for an
Nd/Na heterobimetallic heterogeneous catalyst. Replacing of
NdO1/5(OiPr)13/5/NaHMDS with NdCl3Á6H2O/NaOtBu allowed us to
prepare the catalyst under ambient conditions with a ca. 120-fold
reduction in the cost. The catalyst prepared via the new protocol
was characterized by XRD and STEM, which indicated the catalyst
was essentially identical to that prepared with the original proto-
col, a finding supported by the similar reaction outcomes in
nitroaldol reactions. The new protocol was compatible with MWNT
confinement and the MWNT-confined catalyst was operative in a
continuous-flow platform.
8. For anti-selective catalytic asymmetric nitroaldol reactions, see: (a) Handa, S.;
Nagawa, K.; Sohtome, Y.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed.
2008, 47, 3230; (b) Sohtome, Y.; Kato, Y.; Handa, S.; Aoyama, N.; Nagawa, K.;
Matsunaga, S.; Shibasaki, M. Org. Lett. 2008, 10, 2231; (c) Uraguchi, D.;
Nakamura, S.; Ooi, T. Angew. Chem., Int. Ed. 2010, 49, 7562; (d) Lang, K.; Park, J.;
Hong, S. Angew. Chem., Int. Ed. 2012, 51, 1620; (e) Xu, K.; Lai, G.; Zha, Z.; Pan, S.;
Chen, H.; Wang, Z. Chem. Eur. J. 2012, 18, 12357; For partially successful
(moderate stereoselectivity) examples, see: (f) Blay, G.; Domingo, L. R.;
Hernández-Olmos, V.; Pedro, J. R. Chem. Eur. J. 2008, 14, 4725; (g) Ube, H.;
Terada, M. Bioorg. Med. Chem. Lett. 2009, 19, 3895; (h) Noole, A.; Lippur, K.;
Metsala, A.; Lopp, M.; Kanger, T. J. Org. Chem. 2010, 75, 1313; (i) Blay, G.;
Hernández-Olmos, V.; Pedro, J. R. Org. Lett. 2010, 12, 3058; (j) Ji, Y. Q.; Qi, G.;
Judeh, Z. M. A. Eur. J. Org. Chem. 2011, 4892; (k) Yao, L.; Wei, Y.; Wang, P.; He,
W.; Zhang, S. Tetrahedron 2012, 68, 9119; (l) Boobalan, R.; Lee, G.-H.; Chen, C.
Adv. Synth. Catal. 2012, 354, 2511; (m) Arai, T.; Joko, A.; Sato, K. Synlett 2015,
209.
9. For reviews for the utility of amide-based ligand 1 in combination with rare-
earth metals, see: (a) Kumagai, N. Chem. Pharm. Bull. 2011, 59, 1; (b) Kumagai,
N.; Shibasaki, M. Angew. Chem., Int. Ed. 2013, 52, 223.
10. (a) Ogawa, T.; Kumagai, N.; Shibasaki, M. Angew. Chem., Int. Ed. 2013, 52, 6196;
(b) Sureshkumar, D.; Hashimoto, K.; Kumagai, N.; Shibasaki, M. J. Org. Chem.
2014, 79, 3272; (c) Hashimoto, K.; Kumagai, N.; Shibasaki, M. Org. Lett. 2014,
16, 3496.
Acknowledgments
11. Retail prices of Nd and Na salts are summarized in Supplementary material.
12. (a) Schuetz, S. A.; Way, V. W.; Sommer, R. D.; Rheingold, A. L.; Belot, J. A. Inorg.
Chem. 2001, 40, 5292; (b) Dash, A. K.; Razavi, A.; Mortreux, A.; Lehmann, C. W.;
Carpentier, J.-F. Organometallics 2002, 21, 3238.
This work was financially supported by ACT-C, JST, and
KAKENHI (20229001) from JSPS. N.K. thanks the Japan Agency for
Medical Research and Development (AMED) for financial support.
SCAS (Sumika Chemical Analysis Service) is gratefully thanked for
XRD and STEM analyses.
13. Grinded NdCl3Á6H2O was used to reduce the fluctuation depending on the
production lot.
14. Representative experimental procedure:
A
flame dried test tube (20 mL)
3-way glass stopcock was
equipped with magnetic stirring bar and
a
a
charged with NdCl3Á6H2O (4.3 mg, 0.012 mmol), and dried under vacuum at
room temperature. Ar was backfilled (evacuation/backfill was repeated for
several times) to the test tube, and THF (100 lL) and ligand 1 (200 lL,
Supplementary data
0.012 mmol, 0.6 M/THF) were added successively by well-dried syringes and
needles at room temperature. After stirring the resulting slightly cloudy
solution at 60 °C for 30 min, NaOtBu (36
lL, 0.072 mmol, 2.0 M/THF) was
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.03.
041.
added dropwise at the same temperature. After stirring the resulting mixture
at 60 °C for 1 h (white precipitate appeared), the mixture was cooled to room
temperature and nitroethane (3) (86
was partly dissolved). Self-assembly of Nd/Na catalyst initiated in
l
L, 1.2 mmol) was added (the precipitate
few
a
minutes and the resulting mixture was stirred at room temperature for 12 h to
give a thick white suspension. The whole suspension was transferred to an
Eppendorf tube and the tube was centrifuged at ca. 104 rpm for 30 s. The
supernatant was decanted and dry THF (1.2 mL) was added to the precipitate.
The tube was agitated using a vortex mixer for 30 s and the resulting tube was
centrifuged again, then the supernatant was decanted (washing process). The
resulting precipitate was agitated with dry THF (1.6 mL) and the resulting
suspension was transferred to a flame-dried test tube (20 mL) for the nitroaldol
reaction.
References and notes
1. Henry, L. C. R. Hebd. Seances Acad. Sci. 1895, 120, 1265.
2. For recent reviews, see: (a) Boruwa, J.; Gogoi, N.; Saikia, P. P.; Barua, N. C.
Tetrahedron: Asymmetry 2006, 17, 3315; (b) Palomo, C.; Oiarbide, M.; Laso, A.
Eur. J. Org. Chem. 2007, 2561; (c) Blay, G.; Hernández-Olmos, V.; Pedro, J. R.
Synlett 2011, 1195.
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Synlett 2006, 2699.
15. Although the use of 5-fold excess of NaOtBu is sufficient for complexation (3-
fold for trivalent Nd and 2-fold for two phenolic protons of 1), 6-fold excess of
NaOtBu is recommended for higher reproducibility.
4. (a) Sasai, H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J. Am. Chem. Soc. 1992,
114, 4418; (b) Sasai, H.; Tokunaga, T.; Watanabe, S.; Suzuki, T.; Itoh, N.;
Shibasaki, M. J. Org. Chem. 1995, 60, 7388.
16. See Supplementary material for details.
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