L-proline-derived tertiary amino alcohols as chiral ligands for enantioselective addition of diethylzinc to aldehydes

Article abstract of DOI:10.2174/157017811797249380

A series of L-proline derived tertiary amino alcohols was used as chiral ligands in the asymmetric addition reaction of Et₂Zn to aldehydes. Among these ligands, it was found that ligand 1b which has the biggest steric and electrondonating substituent at the nitrogen position yielded the highest enantioselectivities when applied in the catalytic asymmetric addition of diethylzinc to p-chlorobenzadehyde. The experiment results of our paper may supply useful experience to help in revealing the relationship between ligand structure and ee values of the products.

Full text of DOI:10.2174/157017811797249380

582
Letters in Organic Chemistry, 2011, 8, 582-586
L-Proline-Derived Tertiary Amino Alcohols as Chiral Ligands for Enanti-
oselective Addition of Diethylzinc to Aldehydes
Zhou Xu*,a, Rongcheng Bob, Nan Wuc, Yu Wanb and Hui Wu*,b
aDepartment of Chemistry, Xuzhou Medical College, Xuzhou 221004, P. R. China; bCollege of Chemistry and Chemical
c
Engineering, Xuzhou Normal University, 221116, P. R. China; Department of Aviation Oil and Material, Xuzhou Air-
force College, Xuzhou 221110, P. R. China
Received May 04, 2011: Revised May 19, 2011: Accepted June 17, 2011
Abstract: A series of L-proline derived tertiary amino alcohols was used as chiral ligands in the asymmetric addition re-
action of Et2Zn to aldehydes. Among these ligands, it was found that ligand 1b which has the biggest steric and electron-
donating substituent at the nitrogen position yielded the highest enantioselectivities when applied in the catalytic asym-
metric addition of diethylzinc to p-chlorobenzadehyde. The experiment results of our paper may supply useful experience
to help in revealing the relationship between ligand structure and ee values of the products.
Keywords: Diethyl zinc, enantioselectivity, secondary alcohol, tertiary amino alcohol.
INTRODUCTION
formation and stability of the transition state. Comparing
ligands 1a-1b with 1c-1d, we can see that the N atom of the
ligand linked with electron-donating group gives much better
ee values than electron-withdrawing ones. This phenomenon
is same with the addition reaction of phenylacetene to alde-
hydes when using these tertary amino alcohols as the
ligands. Ligand 1b which has a more bulky substituent at the
nitrogen position than 1a yielded higher enantioselectivity.
This indicated that the three methyl group of the benzen ring
employed important roles during the ethylation of 4-
chlorobenzaldehyde.
Chiral alcohols are important and versatile building
blocks for many natural products and drugs [1-3]. One of the
most useful methods for the asymmetric preparation of sec-
alcohols is the enantioselective addition of dialkylzinc rea-
gents to aldehydes in the presence of chiral ligands [4-27].
Although many existing chiral ligands can induce good to
excellent selectivity, it is still desirable to develop new chiral
catalysts which are greatly needed to probe how the chiral
catalysts act on the reaction and to help us understand how to
design new types of chiral ligands more successfully. In this
way, we could get conclusions or rules between the soft or
hard coordinative atoms of the chiral ligand and the central
metal.
Ph
Ph
N
Ph
N
Ph
HO
HO
For the long run, our research interests focus on explor-
ing the N,O-ligands to apply in asymmetric reactions [28-
31]. Recently, we have reported the enantioselective addition
of terminal alkynes to aldehydes using the tertiary amino
alcohols ligands [28]. As the continuation of this work, we
were destined to explore the application of the L-proline-
derived tertiary amino alcohols as chiral ligands for other
asymmetric reactions. Herein, we report the enantioselective
addition of diethylzinc to aldehydes in the presence of these
ligands and the relationship between ligands and ee values of
the products was also discussed in this paper.
1b
1a
62%ee, R
36% ee, R
Ph
Ph
Ph
N
O
Ph
O
HO
N
S
HO
EtO2C
1c
3.5% ee, S
Scheme 1.
O
RESULTS AND DISCUSSION
1d
With ligands 1a-1d in hand, we examined the use of each
of them in the ethylation of 4-chlorobenzaldehyde (Scheme
1). Ligand 1b gave the highest ee with R configuration when
the amount of ligand was 10 mol%. The substituent on the
nitrogen atom of the chiral catalysts may also affect the
16% ee, R
1b was then chosen as the ligand for further studies. To
optimize the reaction conditions, solvent was first screened.
As can be seen from Table 1, when the reaction was carried
out in DCM, the best result was obtained with 75% ee of the
product (Table 1, entries 1-6). For some asymmetric dieth-
ylzinc addition reactions that can be catalyzed by titanium
*Address correspondence to this author at the Department of Chemistry,
Xuzhou Medical College, Xuzhou 221004, P. R. China; Tel: +86-516-
852980403; Fax: 0516-83500065; E-mail: xuzhou@xzmc.edu.cn
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers

L-Proline-Derived Tertiary Amino Alcohols
Letters in Organic Chemistry, 2011, Vol. 8, No. 8
583
Table 1. Screening of the Reaction Conditionsa
Entry
Solvent
Yield(%)
ee(%)g
1
2
toluene
THF
75
68
62
64
3
4
DCM
Et2O
100
100
100
100
74
75
65
5
5
DMF
6
Hexane
Toluene
DCM
DCM
DCM
DCM
61
28
64
70
68
71
7b
8c
9d
10e
11f
89
79
92
84
aThe reaction conditions: aldehyde (0.5 mmol), Et2Zn (2.0 ml), 1b (0.05 mmol), DCM (1.0 ml), room temperature, 24 h.
bTi(OiPr)4 (0.05 mmol) was added.
cThe reaction was carried out at 0 oC.
dThe reaction was carried out at -10 oC.
e20 mol% 1b was used.
f30 mol% 1b was used.
gThe ee was determined by HPLC using Chiralcel OD-H column and the absolute configuration of the product is R [32].
complexes, 10 mol% Ti(OiPr)4 was used as an additive in the
reaction. However, only 28% ee of the product was observed
(Table 1, entry 7). Since many successful enantiomeric syn-
theses were performed at low temperature, we carried out
this reaction at different temperatures. The results indicated
that reducing the reaction temperature did not enhance the ee
of the product (Table 1, entries 3, 8-9). Therefore, we carried
out the reaction in DCM at room temperature in the follow-
ing experiments. The optimization for the catalyst loading
showed that a 10 mol % of ligand loading was the best com-
promise for reaction yield and enantioselectivity (Table 1,
entries 3, 10-11).
EXPERIMENTAL
All manipulations were carried out under an argon at-
mosphere in dried and degassed solvents. Diethylzinc was
purchased from Aldrich (St. Louis, MO). The reactions were
monitored by thin layer chromatography (TLC). NMR spec-
tra were measured in CDCl3 on a Varian-Inova-400 NMR
spectrometer with TMS as an internal reference. Enanti-
omeric excess (ee) determination was carried out using a
chiral AD-H column or OD-H column. Solvent, hex-
ane/isopropanol.
General Experimental Procedure
Under the optimized conditions of entry 3 in Table 1, the
reactions of ethylation of different aldehydes catalyzed by 1b
were investigated. As shown by the results summarized in
Table 2, moderate to good enantioselectivities were achieved
for most of the aromatic aldehydes. Moderate ee (61%) can
also be obtained with aliphatic aldehyde (Table 2, entry 9).
The electronic character of the arenecarbaldehyde derivative
seemed to have an important impact on the results, since
benzaldehyde derivatives with electron withdrawing groups
gave better results than electron-donating one (Table 2, en-
tries 1-2, 4, 8 and 11-13). Surprisingly, the best result was
obtained by 4-iodobenzaldehyde with 99% ee (Table 2, entry
8). This phenomena is the same with literature reported [34].
Iodine atom may have some special effect on this reaction.
The cyano derivative also gave excellent ee in this series
which may be due to the presence of the chelating group of
CN (Table 2, entry 13).
A solution of ligand 1b (0.05 mmol, 19.2 mg) was dis-
solved in dry DCM (2 ml) under Ar in a schlenk tube and
diethylzinc (2 mL, 1 M in hexane, 2.0 mmol) was added
dropwise. The mixture was stirred at room temperature for 2
h. Then the aldehyde (0.5 mmol) was added and the reaction
mixture was stirred for another 24 h. The reaction was
quenched with 1 M HCl (5 mL). The mixture was extracted
with ethyl acetate (EtOAc) (2 ꢀ 10 ml). The organic layer
was dried over Na2SO4 and concentrated under vacuum. The
residue was purified by flash column chromatography (silica
gel H, EtOAc: Petroleum ether = 1: 6) to give the pure prod-
uct.
SPECTRAL DATA
Ligands 1a-1c have been reported by us [21].
Ligand 1d: H1 NMR (CDCl3, TMS): 7.64 (d, J = 7.6 Hz,
2H), 7.35 (t, J = 7.6 Hz, 2H), 7.25-7.20 (m, 3H), 7.16 (t, J =
7.2 Hz, 1H), 5.21 (s, 1H), 4.78 (t, J = 7.6 Hz, 1H), 3.18–3.17
(m, 1H), 3.09–3.05 (m, 2H), 2.60–2.52 (m, 2H), 2.38–2.32
(m, 1H), 2.08–2.04 (m, 3H), 1.91–1.87(m, 3H), 1.68–1.56
(m, 2H), 1.42–1.36 (m, 1H), 1.09 (s, 3H), 0.86 (s, 3H); 13C
NMR (100 MHz, CDCl3): 216.8, 144.3, 144.1, 128.9, 128.3,
127.7, 126.9, 126.4, 125.3, 77.6, 65.3, 58.4, 48.0, 47.7, 47.2,
In conclusion, we have found a new discovery of ligand
substituents effect in the asymmetric addition of diethylzinc
to aldehydes. The more bulky substituent group on the N
atom of the L-proline derived ligands did cause a signifi-
cantly higher enantioselectivity in the alkylation of aryl al-
dehydes. With the modified ligand 1b in hand, it was used to
catalyze the ethylation of aldehydes with moderate to good
ee of the sec-alcohols (up to 99% ee).

584 Letters in Organic Chemistry, 2011, Vol. 8, No. 8
Xu et al.
Table 2. Scopes of the Reactiona
OH
1b (10 mol%)
R
CHO
R
Et2Zn, DCM, r.t
Entry
R
Yield(%)b
ee(%)c
1
2
4-Cl-C6H4
4-Br-C6H4
100
100
100
88
75
58
51
57
63
7
3
2-Cl-4-Cl-C6H3
2-OMe-3-OMe-C6H3
2-naphthyl
4
5
56
6
4-OMe-C6H4
2-Me-3-Me-C6H3
4-I-C6H4
17
7
59
57
>99d
61
46
68
61
98
8
80
9
Ph-CH2-CH2
C6H5
72
10
11
12
13
100
54
2-Cl-C6H4
3-F-C6H4
100
80
4-CN-C6H4
aThe reaction conditions: aldehyde (0.5 mmol), Et2Zn (2.0 ml), 1b (0.05 mmol), DCM (1.0 ml), room temperature, 24 h.
bIsolated yield after column chromatography.
cThe ee was determined by HPLC using Chiralcel columns and the absolute configuration of the product is R determined by comparing with the literatures [33].
dOnly one enantiomer detected.
42.9, 42.7, 27.1, 26.7, 24.7, 24.6, 20.0, 19.9. HRMS (EI) calc
for [C20H23NO3]+ requires m/z 467.6205, found 467.6211.
3H), 2.41 (s, 1H), 1.85–1.72 (m, 2H), 0.95 (t, J = 7.6 Hz,
3H).
1-(4-chlorophenyl)propan-1-ol
1-(naphthalen-2-yl)propan-1-ol
100% yield. 75% ee determined by HPLC analysis
(Chiralcel OD-H column, IPA: hexane = 1: 99). 1.0 mL/min,
Retention time: tmajor = 12.27 min, tminor = 14.13 min. H1
NMR (CDCl3, TMS): ꢀ 7.31 (d, J = 8.4Hz, 2H), 7.27 (d, J =
8.4 Hz, 2H), 4.58 (t, J = 6.4 Hz, 1H), 2.17 (s, 1H), 1.83–1.68
(m, 2H), 0.90 (t, J = 7.2 Hz, 3H).
56% yield. 63% ee determined by HPLC analysis
(Chiralcel OD-H column, IPA: hexane = 10: 90). 0.5
mL/min, Retention time: tmajor = 18.49 min, tminor = 21.55
min. H1 NMR (CDCl3, TMS): ꢀ 7.84–7.82 (m,3H), 7.67
(s,1H), 7.48–7.45 (m,3H), 4.76 (t, J = 6.4 Hz,1H), 1.99
(s,1H), 1.94–1.81 (m,2H), 0.94 (t, J = 7.6 Hz,3H).
1-(4-bromophenyl)propan-1-ol
1-(4-methoxyphenyl)propan-1-ol
100% yield. 58% ee determined by HPLC analysis
(Chiralcel OD-H column, IPA: hexane = 3: 97). 0.5 mL/min,
Retention time: tmajor = 21.96 min, tminor = 24.13 min. H1
NMR (CDCl3, TMS): ꢀ 7.37 (d, J = 8.4 Hz, 2H), 7.11 (d, J =
8.0 Hz, 2H), 4.46 (t, J = 6.4 Hz, 1H), 2.00 (s, 1H), 1.73–1.58
(m, 2H), 0.81 (t, J = 7.6 Hz, 3H).
17% yield. 7% ee determined by HPLC analysis (Chiral-
cel OD-H column, IPA: hexane = 5: 95). 0.5 mL/min, Reten-
tion time: tmajor = 21.87 min, tminor = 20.64 min. H1 NMR
(CDCl3, TMS): ꢀ 7.18 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.4
Hz, 2H), 4.47 (t, J = 6.4 Hz,1H), 3.73 (s, 3H), 1.80–1.18 (m,
3H), 0.82 (t, J = 7.2 Hz, 3H).
1-(2,4-dichlorophenyl)propan-1-ol
1-(2,3-dimethylphenyl)propan-1-ol
100% yield. 51% ee determined by HPLC analysis
(Chiralcel OD-H column, IPA: hexane = 5: 95). 1.0 mL/min,
Retention time: tmajor = 15.64 min, tminor = 17.94 min. H1
NMR (CDCl3, TMS): ꢀ 7.56–7.48 (m, 1H), 7.39–7.34 (m,
1H), 7.29–7.15 (m, 2H), 5.02 (td, 1H, J = 4.6 Hz, J = 8.9
Hz), 2.00 (s, 1H), 1.83–1.66 (m, 2H), 0.98 (t, J = 7.2 Hz,
3H).
59% yield. 57% ee determined by HPLC analysis
(Chiralcel OD-H column, IPA: hexane = 1: 99). 1.0 mL/min,
Retention time: tmajor = 13.63 min, tminor = 20.19 min. H1
NMR (CDCl3, TMS): ꢀ 7.32 (d, J = 7.6 Hz, 1H), 7.12 (t, J =
7.6 Hz, 1H), 7.07 (d, J = 7.6 Hz, 1H), 4.91 (t, J = 6.4 Hz),
2.29 (s, 3H), 2.22 (s, 3H), 1.78–1.71(m, 3H), 1.26 (s, 3H),
0.98(t, J = 7.2 Hz).
1-(2,3-dimethoxyphenyl)propan-1-ol
1-(4-iodophenyl)propan-1-ol
88% yield. 57% ee determined by HPLC analysis
(Chiralcel OD-H column, IPA: hexane = 5: 95). 0.5 mL/min,
Retention time: tmajor = 26.09 min, tminor = 32.57 min. H1
NMR (CDCl3, TMS): ꢀ 7.04 (t, J = 8.0 Hz,1H), 6.93 (d, J =
7.6 Hz,1H), 4.84 (t, J = 6.8 Hz,1H), 3.86 (s, 3H), 3.85 (s,
80% yield. >99% ee determined by HPLC analysis
(Chiralcel OD-H column, IPA: hexane = 3: 97). 0.5 mL/min,
Retention time: tminor = 12.09 min, tmajor = 26.97 min. H1
NMR (CDCl3, TMS): ꢀ 7.67 (d, J = 8.0 Hz, 2H), 7.09 (d, J =

L-Proline-Derived Tertiary Amino Alcohols
Letters in Organic Chemistry, 2011, Vol. 8, No. 8
585
[3]
[4]
Oguni, N.; Omi, T. Enantioselective addition of diethylzinc to
benzaldehyde catalyzed by a small amount of chiral 2-amino-1-
alcohols. Tetrahedron Lett., 1984, 25, 2823–2824.
8.0Hz, 2H), 4.57 (t, J = 6.4Hz, 1H), 1.80–1.68 (m, 2H), 0.91
(t, J = 7.2 Hz, 3H).
Reviews on the asymmetric alkylation, some selected examples: (a)
Noyori, R.; Kitamura, M. Enantioselective addition of organomet-
allic reagents to carbonyl compounds: chirality transfer, multiplica-
tion, and amplification. Angew. Chem., Int. Ed. Engl., 1991, 30,
49–69; (b) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833–856; (c)
Pu, L.; Yu, H. B. Enantioselective addition of organozinc reagents
to aldehydes. Chem. Rev., 2001, 101, 757–824; (d) Knochel, P.;
Singer, R. D. Catalytic asymmetric organozinc additions to
carbonyl compounds. Chem. Rev., 1993, 93, 2117–2188; (e)
Hatano, M.; Miyamoto, T.; Ishihara, K. Preparation and reactions
of polyfunctional organozinc reagents in organic synthesis. Curr.
Org. Chem., 2007, 11, 127–157; (f) Hatano, M.; Ishihara, K.
Recent progress in selective additions of organometal reagents to
carbonyl compounds. Chem. Res., 2008, 8, 143–155; (g) Hatano,
M.; Ishihara, K. Recent progress in the catalytic synthesis of
tertiary alcohols from ketones with organometallic reagents.
Synthesis, 2008, 1647–1675.
1-phenylpentan-3-ol
72% yield. 61% ee determined by HPLC analysis
(Chiralcel AD-H column, IPA: hexane = 3: 97). 1.0 mL/min,
Retention time: tmajor = 11.69 min, tminor = 10.93 min. H1
NMR (CDCl3, TMS): ꢀ 7.30–7.25 (m, 2H), 7.21–7.16 (m,
3H), 3.55 (ddd, J = 4.5 Hz, 8.0 Hz, 12.2 Hz, 1H), 2.80 (ddd,
1H, J = 5.8Hz, 9.8 Hz, 14.1 Hz, 1H), 2.67 (ddd, 1H, J = 6.7
Hz, 9.7 Hz, 13.8 Hz, 1H), 1.84–1.76 (m, 2H), 1.56–1.41 (m,
3H), 0.94 (t, J = 7.2 Hz, 3H).
1-phenylpropan-1-ol
100% yield. 46% ee determined by HPLC analysis
(Chiralcel OD-H column, IPA: hexane = 3: 97). 0.5 mL/min,
Retention time: tmajor = 24.90 min, tminor = 21.35 min. H1
NMR (CDCl3, TMS): ꢀ 7.35–7.27 (m, 5H), 4.59 (t, J = 6.8
Hz,1H), 1.87 (s, 1H), 1.86–1.71 (m, 2H), 0.91 (t, J = 7.2 Hz,
3H).
[5]
Ye, M.; Logaraj, S.; Jackman, L. M.; Hillegass, K.; Hirsh, K. A.;
Bollinger, A. M.; Grosz, A. L.; Mani, V. Enantioselective addition
of alkyllithium reagents to aldehydes induced by chiral lithium
alkoxides. Tetrahedron, 1994, 50, 6109–6116.
[6]
[7]
Frantz, D.E.; Fassler, R.; Carreira, E. M. Facile enantioselective
synthesis of propargylic alcohols by direct addition of terminal al-
kynes to aldehydes. J. Am. Chem. Soc., 2000, 122, 1806–1807.
Zhu, H. J.; Jiang, J. X.; Saebo, S.; Pittman, Jr C. U. Chiral ligands
derived from abrine 8. An experimental and theoretical study of
free ligand conformational preferences and the addition of dieth-
ylzinc to benzaldehyde. J. Org. Chem., 2005, 70, 261–267.
Lipshutz, B. H.; Shin, Y. L. Polystyrene-bound cyclo-BINOLs:
new heterogeneous ligands for asymmetric catalysis. Tetrahedron
Lett., 2000, 41, 9515–9521.
Dahman, S.; Brase, S. Planar and central chiral
[2.2]paracyclophane-based N,O-ligands as highly active catalysts in
the diethylzinc addition to aldehydes. Chem. Commun., 2002, 26–
27.
1-(2-chlorophenyl)propan-1-ol
54% yield. 68% ee determined by HPLC analysis
(Chiralcel OD-H column, IPA: hexane = 5: 95). 0.5 mL/min,
Retention time: tmajor = 13.51 min, tminor = 19.34 min. H1
NMR (CDCl3, TMS): ꢀ 7.56–7.20 (m, 4H), 5.07 (dd, J = 4.9
Hz, 7.5 Hz, 1H), 1.99 (s, 1H), 1.83–1.72 (m, 2H), 0.99 (t, J =
7.2 Hz, 3H).
[8]
[9]
1-(3-fluorophenyl)propan-1-ol
100% yield. 61% ee determined by HPLC analysis
(Chiralcel AD-H column, IPA: hexane = 3: 97). 1.0 mL/min,
Retention time: tmajor = 11.69 min, tminor = 10.93 min. H1
NMR (CDCl3, TMS): ꢀ 7.32–7.27 (m, 1H), 7.10–7.05 (m,
2H), 6.95 (dt, J = 8.5 Hz, 2.4 Hz, 1H), 4.60 (t, J = 6.4
Hz,1H), 1.91 (s, 1H), 1.81–1.72 (m, 2H), 0.92 (t, J = 7.2 Hz,
3H).
[10]
Pini, D.; Mastantuono, A.; Uccello-Barretta, G.; Iuliano, A.; Salva-
dori, P. Addition of diethylzinc to aryl aldehydes catalyzed by
(1S,3S)-N,N1-bis[benzyl]-1,3-diphenyl-1,3-propanediamine and its
dilithium salt: a mechanistic rationale investigation. Tetrahedron,
1993, 49, 9613–9624.
[11]
[12]
[13]
Rosini, C.; Franzini, L.; Iuliano, A.; Pini, D.; Salvadori, P.
Asymmetric alkylation of aromatic aldehydes by diethyl zinc in the
presence
of
(S)-N,N,Nꢀ,Nꢀ,-tetramethyl-2,2ꢀ-diamino-1,1ꢀ-
binaphthyl. Tetrahedron Asymmetry, 1991, 2, 363–366.
4-(1-hydroxypropyl)benzonitrile
Paquette, L. A.; Zhou, R. J. Synthesis of enantiopure C2-symmetric
VERDI disulfonamides and their application to the catalytic enan-
tioselective addition of diethylzinc to aromatic and aliphatic alde-
hydes. J. Org. Chem., 1999, 64, 7929–7934.
Yoshioka, M.; Kawakita, T.; Ohno, M. Asymmetric induction
catalyzed by conjugate bases of chiral proton acids as ligands:
Enantioselective addition of dialkylzinc-orthotitanate complex to
benzaldehyde with catalytic ability of a remarkable high order. Te-
trahedron Lett., 1989, 30, 1657–1660.
80% yield. 98% ee determined by HPLC analysis
(Chiralcel OD-H column, IPA: hexane = 15: 85). 0.5
mL/min, Retention time: tmajor = 12.11 min, tminor = 15.62
min. H1 NMR (CDCl3, TMS): ꢀ 7.63 (d, J = 8.0 Hz, 2H),
7.45 (d, J = 8.0 Hz, 2H), 4.69 (t, J = 6.4 Hz,1H), 2.13 (s,
1H), 1.83–1.71 (m, 2H), 0.93 (t, J = 7.6 Hz,1H).
[14]
[15]
Cernerud, M.; Skrinning, A.; Bergere, I.; Moberg, C.
Bis(ethylsulfonamide)amines via nucleophilic ring-opening of
chiral aziridines. Application to Ti-mediated addition of diethylzinc
to benzaldehyde. Tetrahedron Asymmetry, 1997, 8, 3437–3441.
Pritchett, S.; Woodmansee, D. H.; Gantzel, P.; Walsh, P. J.
Synthesis and crystal structures of bis(sulfonamido) Titanium
ACKNOWLEDGEMENTS
We are grateful to the grants from the Natural Science
Foundation of Higher Education Institutions of Jiangsu Prov-
ince, China (No. 10KJB150018) and (No. 10KJA430 050)
and Qin Lan Project in Jiangsu Province (NO. 08QLT001)
and the Special Presidential Foundation of Xuzhou Medical
College (2010KJZ15) for financial support.
bis(alkoxide) complexes:
mechanistic implications in the
bis(sulfonamide) catalyzed asymmetric addition of dialkylzinc rea-
gents to aldehydes. J. Am. Chem. Soc., 1998, 120, 6423–6424.
Takahashi, H.; Yoshioka, M.; Kobayashi, S. Catalytic enantioselec-
tive reactions using C2-symmetric disulfonamides as chiral ligands.
J. Syn. Org. Chem. Jpn., 1997, 55, 714–724.
(a) Zhang, F. Y.; Yip, C. W.; Cao, R.; Chan, A. S. C.
Enantioselective addition of diethylzinc to aromatic aldehydes cata-
lyzed by Ti(BINOL) complex. Tetrahedron Asymmetry, 1997, 8,
585–589; (b) Zhang, F. Y.; Chan, A. S. C. Asymmetric catalytic al-
kylation of aldehydes with diethylzinc using a chiral binaphthol-
Titanium complex. Tetrahedron Lett., 1997, 38, 6233–6236.
Rosini, C.; Franzini, L.; Pini, D.; Salvadori, P. Enantioselective
alkylation of prochiral aldehydes by diethylzinc promoted by (S,
[16]
[17]
REFERENCES
[1]
Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley:
New York, 1994.
[2]
Soai, K.; Shibata, T. In Comprehensive Asymmetric Catalysis;
Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H.; Eds.; Springer: Berlin,
Germany, 1999; Vol. 2, pp. 911–922.
[18]

586 Letters in Organic Chemistry, 2011, Vol. 8, No. 8
Xu et al.
S)-1,2-diphenylethan-1,2-diol. Tetrahedron Asymmetry, 1990, 1,
587–588.
[27]
[28]
[29]
Hatano, M.; Mizuno, T.; Ishihara, K. Commercially available neat
organozincs as highly reactive reagents for catalytic enantioselec-
tive addition to ketones and aldehydes under solvent free condi-
tions. Tetrahedron, 2011, 67, 4417–4424.
Xu, Z.; Wu, N.; Ding, Z. H.; Wang, T.; Mao, J. C.; Zhang, Y. W.
L–Proline–derived tertiary amino alcohol as a new chiral ligand for
enantioselective alkynylation of aldehydes. Tetrahedron Lett.,
2009, 50, 926–929.
Xu, Z.; Mao, J. C.; Zhang, Y. W.; Guo, J.; Zhu, J. L. Inversion of
stereochemistry in the asymmetric transfer hydrogenation of ke-
tones performed in tap water and in open-vessel. Catalysis Com-
mun., 2008, 9, 618–623.
Xu, Z.; Mao, J. C.; Zhang, Y. W. Highly enantioselective asymmet-
ric alkynylation of aldehydes catalyzed by a new oxazolidine-
titanium complex. Org. Biomol. Chem., 2008, 1288–1292.
Xu, Z.; Mao, J. C.; Zhang, Y. W. Unmodified chiral primary amino
alcohol as a new ligand for enantioselective alkynylation of alde-
hydes. Catalysis Commun., 2008, 10, 113–117.
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
Nakamura, Y.; Takeuchi, S.; Ohgo, Y.; Curran, D. P. Asymmetric
alkylation of aromatic aldehydes with diethylzinc catalyzed by a
fluorous BINOL–Ti complex in an organic and fluorous biphase
system. Tetrahedron Lett., 2000, 41, 57–60.
Kostova, K.; Genov, M.; Philipova, I.; Dimitrov, V. New bis-
steroidal axially chiral diols as ligands for the asymmetric addition
of diethylzinc to aldehydes. Tetrahedron Asymmetry, 2000, 11,
3253–3256.
Hatano, M.; Miyamoto, T.; Ishihara, K. Enantioselective addition
of organozinc reagents to aldehydes catalyzed by 3,3ꢀ-
Bis(diphenylphosphinoyl)-BINOL. Adv. Synth. & Catal., 2005,
347, 1561–1568.
Hatano, M.; Miyamoto, T.; Ishihara, K. Enantioselective dial-
kylzinc addition to aldehydes catalyzed by chiral Zn(II)-
BINOLates bearing phosphonates and phosphoramides in the 3,3ꢀ-
Positions. Synlett, 2006, 1762–1764.
[30]
[31]
[32]
Hatano, M.; Miyamoto, T.; Ishihara, K. 3,3‘-Diphosphoryl-1,1‘-bi-
2-naphtholꢁZn(II) Complexes as conjugate AcidꢁBase catalysts for
enantioselective dialkylzinc addition to aldehydes. J. Org. Chem.,
2006, 71, 6474–6484.
Hui, A. L.; Zhang, J. T.; Fan, J. M.; Wang, Z. R. A new chiral
sulfonamide ligand based on tartaric acid: synthesis and application
in the enantioselective addition of diethylzinc to aldehydes and ke-
tones. Tetrahedron Asymmetry, 2006, 17, 2101–2107.
Hatano, M.; Miyamoto, T.; Ishihara, K. Highly active chiral phos-
phoramideꢁZn(II) complexes as conjugate acidꢁbase catalysts for
enantioselective organozinc addition to ketones. Org. Lett., 2007, 9,
4535–4538.
Hatano, M.; Mizuno, T.; Ishihara, K. A concise synthesis of (S)-
(+)-ginnol based on catalytic enantioselective addition of commer-
cially unavailable di(n-alkyl)zinc to aldehydes and ketones. Synlett,
2010, 2024–2028.
Hatano, M.; Mizuno, T.; Ishihara, K. Catalytic enantioselective
synthesis of sterically demanding alcohols using di(2°-alkyl)zinc
prepared by the refined Charette's method. Chem. Commun., 2010,
46, 5443–5445.
[33]
[34]
Huang, W. S.; Hu, Q. S.; Pu, L. From highly enantioselective
monomeric catalysts to highly enantioselective polymeric catalysts:
application of rigid and sterically regular chiral binaphthyl poly-
mers to the asymmetric synthesis of chiral secondary alcohols. J.
Org. Chem., 1999, 64, 7940–7956.
Gou, S. H.; Judeh, Z. M. A. Enantioselective addition of dieth-
ylzinc to aromatic aldehydes catalyzed by Ti(IV) complexes of C2-
symmetrical chiral BINOL derivatives. Tetrahedron Lett., 2009,
50, 281-283.