Titanium (IV) as an essential promoter in the asymmetric addition of diethylzinc to aldehydes catalyzed by aminonaphthol and imine ligands based on 3-substituted binaphthol

Article abstract of DOI:10.1016/j.jorganchem.2007.07.003

By using indirect reductive amination and condensation, two types of aminonaphthol and imine ligands based on 3-substituted binaphthol have been synthesized, respectively. When their catalytic effectiveness was tested by the ethylation of aldehydes with diethylzinc, titanium tetraisopropoxide was found essential to get good results with ee up to 90%.

Full text of DOI:10.1016/j.jorganchem.2007.07.003

Journal of Organometallic Chemistry 692 (2007) 4377–4380
www.elsevier.com/locate/jorganchem
Titanium (IV) as an essential promoter in the asymmetric addition
of diethylzinc to aldehydes catalyzed by aminonaphthol and imine
ligands based on 3-substituted binaphthol
*
Fu-Yong Jiang, Bing Liu, Zhi-Bing Dong, Jin-Shan Li
State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China
Received 20 March 2007; received in revised form 30 June 2007; accepted 3 July 2007
Available online 12 July 2007
Abstract
By using indirect reductive amination and condensation, two types of aminonaphthol and imine ligands based on 3-substituted
binaphthol have been synthesized, respectively. When their catalytic effectiveness was tested by the ethylation of aldehydes with dieth-
ylzinc, titanium tetraisopropoxide was found essential to get good results with ee up to 90%.
ꢀ 2007 Elsevier B.V. All rights reserved.
Keywords: Reductive amination; BINOL; Diethylzinc; Titanium tetraisopropoxide
1. Introduction
thol and imine ligands with a scaffold of 3-substituted
BINOL. In this paper, we report the synthesis of chiral
aminonaphthol ligands (S)-1 and (S)-2 as well as imine
ligands (S)-3 and (S)-4, together with their catalytic applica-
bility in the addition of diethylzinc to aldehydes.
Over the past decades, the enantioselective alkylation of
carbonyl compounds has been dramatically improved,
owing to the use of organozinc reagents in the presence of
a wide variety of chiral auxiliaries [1]. And a large number
of chiral catalysts such as b-amino alcohols (particularly
those possessing a tertiary amino group) [2], amino thiols
[3], aminonaphthols [4], imines [5] and titanium complexes
[6] have been developed and high enantioselectivities have
been achieved. Thus, the reaction of diethylzinc with alde-
hydes has become a classical test in the design of new
ligands for catalytic asymmetric synthesis. Despite the enor-
mous success of axially chiral ligands in asymmetric reac-
tions, a limited number of aminonaphthol [7] and imine
[8] type ligands based on BINOL are reported for diethyl-
zinc addition to aldehydes. To the best of our knowledge,
there have never been such type ligands prepared from 3-
formyl BINOL [9] in the long catalyst list of the asymmetric
addition of diethylzinc to aldehydes. Therefore, it should be
of interest to explore the catalytic ability of the aminonaph-
OH
N
N
O
N
N
N
OH
OH
OH
OH
OH
OH
OH
OH
(S)-1
(S)-2
(S)-3
(S)-4
Among the four ligands, (S)-1 is a known compound
synthesized as a byproduct in a short but severe Man-
nich-type procedure with partial racemization [10]. Here
(S)-1 is synthesized under mild reaction condition in high
yield without racemization.
2. Results and discussion
*
(S)-1 and (S)-2 were easily prepared in high yield by
indirect reductive amination of (S)-3-formyl BIONL with
Corresponding author. Fax: +86 22 2350 3627.
E-mail address: jinshan_li2001@yahoo.com.cn (J.-S. Li).
0022-328X/$ - see front matter ꢀ 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2007.07.003

4378
F.-Y. Jiang et al. / Journal of Organometallic Chemistry 692 (2007) 4377–4380
Table 1
morpholine and piperidine in the presence of NaBH4,
respectively [11]. (S)-3 and (S)-4 were also conveniently
prepared from condensation of (S)-3-formyl BINOL with
hydroxylamine hydrochloride and 2-aminopyridine in
good yield (Scheme 1) [12].
Catalytic asymmetric addition of diethylzinc (1.5 M in hexane) to
benzaldehyde using ligands (S)-1–4
OH
*
CHO
(S)-1-4
PhMe
+
Et2Zn
A pale yellow single crystal of rac-3 Æ THF was obtained
from THF-petroleum ether solution. The crystal structure
was determined by X-ray diffraction as shown in Fig. 1
[13]. The oxime has a trans configuration. The torsion angle
of C(20)–C(19)–C(21)–N(1) is 2.1ꢁ, and the dihedral angle
between the two naphthalene systems is 82.3ꢁ.
First, the effectiveness of the four ligands as chiral cata-
lysts for the ethylation of aldehydes with Et2Zn was tested.
The addition reaction was carried out in toluene at room
temperature. Unfortunately, neither the chemical yields
nor the enantioselectivities were satisfactory (Table 1).
Ligand (S)-3 (5 mol%) only gave a 67% yield and 32% ee
as the best result (Entry 3). In addition, the reduced benzyl
alcohol products were also observed in about 15% yield for
(S)-1 and (S)-2 (Entry 1 and 2).
Entry
Ligand (mol%)a
Yield (%)b
ee (%)c
Config.d
1
2
3
4
a
(S)-1 (10)
(S)-2 (10)
(S)-3 (5)
(S)-4 (5)
51 (13)
38 (16)
67
13
16
32
15
S
S
S
S
57
Et2Zn/benzaldehyde = 3:1; reaction temperature: r.t.; reaction time:
48 h.
b
Isolated yield and the data in brackets refers to the amount of benzyl
alcohol product.
c
Data were determined by GC analysis using a chiral column (Chiral
beta-DEX 120 capillary column).
d
The absolute configuration of the products were determined by com-
parison to the literature data.
and it resulted in a dramatic enhancement not only in
chemical yields but in ee values (Table 2). Again, (S)-3
(20 mol%) gave the best result with a 93% yield and 89%
ee in the presence of 1.2 equiv. Ti(OiPr)4 (Entry 4). Fur-
thermore, the reduced benzyl alcohol products were not
detected at all for (S)-1 and (S)-2 (Entry 1–3).
Titanium (IV) complexes with various chiral ligands
have been extensively confirmed as an effective promoter
for the asymmetric addition of diethylzinc to aldehydes in
the last years. Hence, aimed at improving the catalytic per-
formance of the four ligands (S)-1–4, Ti(OiPr)4 was added
With conditions optimized for benzaldehyde, the use of
ligand (S)-3 was extended to the asymmetric ethylation of
other aromatic and a,b-unsaturated aldehydes (Table 3).
The additions were completed within 5 h at room temper-
ature with good yields and ee values for all the aldehydes.
For anisaldehyde possessing an electron-donating group in
para position and trans-cinnamaldehyde, a slight decreased
enantioselectivity was observed (Entry 4 and 6). The best
enantioselectivities up to 90% ee were obtained with p-
bromobenzaldehyde and o-methoxybenzaldehyde (Entry
3 and 5).
i) secondary amine (1.2 eq.)
THF/MeOH, 4 Å MS
4 h, reflux
(S)-1or (S)-2
ii) NaBH4 (2.0 eq.)
0.5 h, r.t.
(S)-1: 96%
(S)-2: 92%
CHO
OH
OH
(S)-3-for`INOL
primary amine (1.2 eq.)
(S)-3 or (S)-4
EtOH, 4 Å MS
12h, reflux
(S)-3: 85%
(S)-4: 70%
Table 2
Addition of diethylzinc (1.5 M in hexane) to benzaldehyde using ligands
(S)-1–4 in the presence of titanium tetraisopropoxide
Scheme 1. Synthesis of (S)-1–4.
OH
Ti(OiPr)4/L*
PhMe
CHO
*
+
Et2Zn
Entry
Ligand (mol%)a
Yield (%)b
ee (%)c
Config.d
1
2
3
4
5
6
7
a
(S)-1 (20)
(S)-1 (10)
(S)-2 (10)
(S)-3 (20)
(S)-3 (10)
(S)-3 (5)
85
83
80
93
90
94
92
76
72
56
89
81
64
31
S
S
S
S
S
S
S
(S)-4 (10)
Ti(OiPr)4/Et2Zn/benzaldehyde = 1.2:3:1; reaction temperature: r.t.;
reaction time: 5 h.
b
Isolated yield.
c
Data were determined by GC analysis using a chiral column (Chiral
beta-DEX 120 capillary column).
d
The absolute configuration of the products were determined by com-
Fig. 1. The molecular structure of 3 including one THF molecule.
parison to the literature data.

F.-Y. Jiang et al. / Journal of Organometallic Chemistry 692 (2007) 4377–4380
4379
Table 3
temperature for 0.5 h. The reaction was then quenched
with 1 M NaOH and the reaction mixture was extracted
with EtOAc. The extract was washed with saturated NaCl
solution and dried over Na2SO4. After removal of the sol-
vent, the residue was purified by column chromatography
on silica gel with petroleum ether/ethyl acetate (3/1) as
eluent.
Addition of diethylzinc (1.5 M in hexane) to aldehydes using ligands (S)-3
in the presence of titanium tetraisopropoxide
Ti(OiPr)4/(S)-3
OH
*
O
+
Et2Zn
PhMe
R
R
H
Entry
Ra
Yield (%)b
ee (%)c
Config.d
1
2
3
4
5
6
7
a
Ph
p-ClC6H4
p-BrC6H4
p-MeOC6H4
o-MeOC6H4
PhCH = CH
1-Naphthyl
93
92
92
85
87
94
96
89
88
90
74
90
80
85
S
S
S
S
S
S
S
4.2.1. (S)-3-morpholinomethyl-1,10-binaphthol [(S)-1]
25
White solid; yield: 96%; ½aꢀD ¼ ꢁ32:5 (c = 0.1, CH2Cl2);
1
m.p. 216–218 ꢁC; H NMR (300 MHz, CDCl3) d: 2.65 (s,
4H), 3.70 (s, 4H), 3.97–4.05 (m, 2H), 5.06 (br, 1H), 7.10-
7.38 (m, 7H), 7.73–7.92 (m, 4H).
(S)-3/Ti(OiPr)4/Et2Zn/aldehyde = 0.2:1.2:3:1; reaction temperature:
r.t.; reaction time: 5 h.
b
4.2.2. (S)-3-piperidinomethyl-1,10-binaphthol [(S)-2]
Isolated yield.
c
25
Data were determined by GC analysis using a chiral column (Chiral
White solid; yield: 92%; ½aꢀD ¼ ꢁ34:7 (c = 0.1, CH2Cl2);
beta-DEX 120 capillary column).
1
m.p. 146–148 ꢁC; H NMR (300 MHz, CDCl3) d: 1.46 (br,
d
The absolute configuration of the products were determined by com-
2H), 1.57–1.60 (m, 4H), 2.58 (br, 4H), 3.93–3.99 (m, 2H),
7.13–7.38 (m, 7H), 7.68–7.91 (m, 4H); 13C NMR
(75 MHz, CDCl3) d: 24.0, 25.7, 54.1, 62.7, 110.0, 112.6,
115.4, 117.8, 123.4, 123.7, 124.7, 125.2, 126.5, 127.0,
127.9, 128.4, 128.5, 129.1, 129.5, 130.0, 133.8, 134.1,
151.5, 155.6; IR (KBr): 3313, 2937, 1622, 1506, 1427, 812,
parison to the literature data.
3. Conclusions
740 cmꢁ1
;
HR-MS Calc. for C26H26NO2 (M++H):
In conclusion, we have prepared aminonaphthol and
imine type ligands (S)-1–4 from (S)-3-formyl BINOL con-
veniently. Their catalytic effectivities were tested by the
ethylation of Et2Zn to aldehydes, and the imine type ligand
(S)-3 gave the best results with high yields and good ee val-
ues in the presence of Ti(OiPr)4.
384.1964. Found: 384.1954.
4.3. Preparation of (S)-3-(N-hydroxyl)iminoformyl-1,
10-binaphthol [(S)-3]
To a solution of (S)-3-formyl BINOL (2 mmol) in dry
4. Experimental
EtOH (20 mL) were added NaOAc (4 mmol), powdered
and activated 4 A molecular sieves (excess) and hydroxyl-
˚
4.1. General
amine hydrochloride (2.4 mmol) in turn. The mixture was
stirred under reflux for 12 h. The 4 A MS were filtered off
˚
1
The H and 13C NMR spectra were recorded on a Bru-
and the solvent was evaporated under vacuum. To the res-
idue were added EtOAc (20 mL) and water (20 mL). After
shaking the organic layer was separated, dried over Na2SO4
and concentrated to solvent free. The remaining solid was
recrystallized from petroleum ether/dichloromethane to
ker AC-300 instrument in CDCl3 solution with TMS as
internal standard. Optical rotations were measured on a
Perkin–Elmer 241 polarimeter. IR spectra were recorded
as KBr plates on a Bruker Equinox 55 spectrometer. The
high-resolution mass spectra (MALDI-HRMS) were mea-
sured on an Ionspec FT MS 7.0 T spectrometer. All exper-
iments which are sensitive to moisture or air were carried
out under an argon atmosphere using standard Schlenk
techniques. Diethylzinc (1.5 M solution in hexane) was
purchased from Aldrich. All anhydrous solvents were puri-
fied and dried by standard techniques just before use.
25
give a pale yellow solid. Yield: 85%; ½aꢀD ¼ ꢁ89:6
1
(c = 0.1, CH2Cl2); m.p. 254–256 ꢁC; H NMR (300 MHz,
CDCl3)d: 4.98 (s, 1H), 7.08–7.41 (m, 7H), 7.86–7.95 (m,
3H), 8.50 (s, 1H), 9.97 (s, 1H); 13C NMR (75 MHz, CDCl3)
d: 110.1, 112.4, 114.3, 118.6, 122.8, 123.6, 124.8, 126.2,
126.4, 127.7, 128.2, 128.4, 128.7, 129.1, 129.4, 130.7,
131.8, 134.6, 138.1, 145.7, 151.9; IR (KBr): 3342, 1622,
1586, 1506, 1427, 1340, 1282, 812, 740 cmꢁ1; HR-MS Calc.
for C21H16NO3 (M++H): 330.1130. Found: 330.1119.
4.2. Typical procedure for the preparation of (S)-1 and
(S)-2
4.4. Preparation of (S)-3-(N-pyridin-2-yl)iminoformyl-1,
10-binaphthol [(S)-4]
Under an argon atmosphere (S)-3-formyl BINOL
(2 mmol) and morpholine or piperidine (2.4 mmol) were
mixed in THF (20 mL) and MeOH (5 mL) in the presence
To a solution of (S)-3-formyl BINOL (2 mmol) in dry
˚
˚
of 4 A molecular sieves at room temperature. After reflux-
EtOH (20 mL) were added 4 A MS (excess) and 2-amino-
ing for 4 h, the reaction mixture was cooled to 0 ꢁC.
Sodium borohydride (4 mmol) was added portionwise
and the resulting mixture was continuously stirred at room
pyridine (2.4 mmol). The mixture was stirred under reflux
for 12 h. The 4 A MS were filtered off, and the solvent
was evaporated under vacuum. The remaining solid was
˚

4380
F.-Y. Jiang et al. / Journal of Organometallic Chemistry 692 (2007) 4377–4380
recrystallized from petroleum ether/dichloromethane to
References
25
give a yellow solid. Yield: 70%; ½aꢀD ¼ ꢁ207 (c = 0.1,
1
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mmol) in toluene (3 mL) was added diethylzinc (2.0 mL,
1.5 M solution in hexane). After stirring at room tempera-
ture for 0.5 h, benzaldehyde was added and the mixture
was stirred for 48 h. The reaction was quenched with
20 mL of saturated NH4Cl solution, and the mixture was
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in 3 mL of toluene at room temperature and the mixture
was stirred for 15 min followed by addition of diethylzinc
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Acknowledgement
This work was supported by the National Natural Sci-
ence Foundation of China (Grant No. 20372037).
Appendix A. Supplementary material
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CCDC 640939 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge via http://www.ccdc.cam.ac.uk/conts/retriev-
ing.html, or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
(+44) 1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.jorganchem.
2007.07.003.
[13] Crystal data for rac-3 Æ THF: C25H23NO4, M = 401.44, triclinic, space
ꢀ
˚
˚
˚
group P1, a = 8.823(8) A, b = 11.487(8) A, c = 11.591(9) A, a =
3
˚
62.78(3)ꢁ, b = 78.67(4)ꢁ, c = 76.47(4)ꢁ, V = 1010.2(14) A , Z = 2,
Dc = 1.320 g cmꢁ3
,
Mo Ka (k = 0.71070 A), T = 113(2) K, l =
˚
0.089 mmꢁ1, crystal size (mm) 0.16 · 0.16 · 0.16. Area detector data
were collected on a MicroMax-007 diffractometer. A total of 7655
reflections were collected (1.99 < h < 25.02). Structure solution by
direct method (SHELXS-97), refinement by full-matrix least squares on
F2, R1 = 0.0840, wR2= 0.2527, GOF = 1.199.