Synthesis of enantiopure C3-symmetric bulky trialkanolamines and their enantioselective inductivity during the alkynylation of aldehydes

Article abstract of DOI:10.1016/j.jorganchem.2014.10.027

Several C₃-symmetric trialkanolamines can be efficiently obtained via molecular sieve-assisted epoxide ring opening with ammonia in high yields (up to 90%) and regioselectivity up to 100%. These trialkanolamines were effective for the asymmetri

Full text of DOI:10.1016/j.jorganchem.2014.10.027

Journal of Organometallic Chemistry 775 (2015) 88e93
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis of enantiopure C -symmetric bulky trialkanolamines and
3
their enantioselective inductivity during the alkynylation of aldehydes
*
*
An-Lin Zhang, Li-Wen Yang , Nian-Fa Yang , Jing Zhang
Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University,
Hunan 411105, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 August 2014
Received in revised form
Several C -symmetric trialkanolamines can be efficiently obtained via molecular sieve-assisted epoxide
ring opening with ammonia in high yields (up to 90%) and regioselectivity up to 100%. These tri-
3
alkanolamines were effective for the asymmetric alkynylation of aldehydes and the propargyl alcohols
13 October 2014
1
were obtained in high yields (up to 92%) and high enantiomeric excesses (up to 95%). The H NMR spectra
Accepted 21 October 2014
Available online 30 October 2014
support that there could be a complex mixture of polynuclear Ti(IV)-based species form from the
interaction of Ti(IV) with ligand.
©
2014 Elsevier B.V. All rights reserved.
Keywords:
3
C -Symmetric
Trialkanolamines
Enantioselective
Phenylacetylene
Introduction
higher stability [11e14]. A Cu complex of one of 3-substituted
tris(pyrazolyl)hydroborates was shown to catalyze the cyclo-
propanation of styrene with diazoesters with up to 60% ee [15]. In
C
3
Symmetry is a fascinating subject not only in visual art, but
also in other subjects, especially in chemistry. The chemists from all
over the world has paid much attention to C symmetry, especially
I
II
contrast to trispyrazolyl ligands, Cu and Cu complexes of chiral
analogues of C -symmetric tripodal trisdihydrooxazole ligand were
3
3
in asymmetric catalysis and chiral molecular recognition [1]. The
selective recognition of one enantiomer out of its racemic mixture
requires an artificial receptor that provides an effective chiral
environment toward one enantiomeric guest over another. Among
a variety of chiral molecular receptors with different molecular
shown to catalyze the oxidation of cyclopentene with tert-butyl
perbenzoate in up to 84% ee [16]. Some tridentate tris(oxazoline)
ligands have been developed as chiral auxiliaries in asymmetric
catalytic reaction such as allylic oxidation of cycloalkenes [17,18],
Michael addition [19,20], FriedeleCrafts reaction [21], coupling of
terminal acetylenes and nitrones [22], Kinugasa reaction [23],
DielseAlder reaction [24] and cycloaddition of nitrones to alkyli-
dene malonates [25]. Recently W.A. Nugent et al. reported a new
symmetries, C
Phosphane ligands have been the most commonly studied ligands
for application in homogeneous catalysis, C -Symmetric mono-
3
-symmetric receptors have been widely used [2e6].
3
phosphanes or triphosphanes carrying three identical chiral groups
were used in early investigations of enantioselective catalytic re-
actions. For example, the rhodium(I) complexes of enantiomerically
3
class of Ti(IV) and Zr(IV)/C trialkanolamine complexes that effi-
ciently catalyze stereoselective processes such as meso-epoxide
ring opening [26], halohydrin synthesis [27] and sulfoxidation of
aryl alkyl sulfides [3,28].
3
pure tripodal phosphanes with C -symmetry have been reported in
the hydrogenation of dimethyl itachonate giving high ee (95%) [7,8].
In recent years nitrogen-based ligands such as pyridine derivatives
Although many significant results have been achieved in this
area, much effort to develop new types of efficient chiral catalysts
for this important asymmetric reaction is still in great need to
probe the relation between the ligand structure and catalytic ac-
[9,10] have replaced those containing phosphorus in many re-
actions mainly due to their ease of preparation and their often
3
tivity. To the best of our knowledge, no C -symmetric chiral tri-
alkanolamine ligand or catalyst has been successfully employed to
the reaction of alkynylzinc addition to aldehydes. Herein, we report
a new approach in which C
gands combined with Ti(O-i-Pr)
tioselective alkynylation of aldehydes.
3
-symmetric chiral trialkanolamine li-
*
Corresponding authors.
E-mail addresses: yangliwen_0519@163.com (L.-W. Yang), nfyang@mail.sdu.edu.
4
are used to catalyze the enan-
cn (N.-F. Yang).
http://dx.doi.org/10.1016/j.jorganchem.2014.10.027
0
022-328X/© 2014 Elsevier B.V. All rights reserved.

A.-L. Zhang et al. / Journal of Organometallic Chemistry 775 (2015) 88e93
89
Result and discussion
Table 1
Molecular sieve-assisted synthesis of enantiopure (S,S,S)-triisopropanolamine
a
2aed.
2
During our previous studies, a series of C -symmetric ligands
were easily prepared from commercially available epichlorohydrin
ECH), which were highly effective for the alkylation of aldehydes
up to 96% ee) [29,30]. It is also well known that enantioselectivities
of chiral ligand-catalyzed reactions are always related to the steric
effects of ligands besides their electronic effects [31,32]. Given
these, we speculate that enantiopure, C -symmetric trialkanol-
3
amines with adjustable steric hindrance could be efficiently ob-
tained via bulky chiral propylene oxides [33]. The synthesis of a
Entry
Substrate
Conversion %c
2:3:4d
Yield (2) %e
De (2) %f
(
(
1
2
3
4
5
b
1a
1a
1b
1c
1d
62
95
>99
>99
92
45:35:20
85:12:3
82:10:8
>90:5:5
>90:5:5
43
82
85
88
90
98
98
98
97
96
a
ꢀ
Reaction condition: solvent: methanol temperature:160 C; reaction time: 48 h;
the quality of 4 Å molecular sieve: 1 g.
b
No molecular sieve was added.
new library of C
3
-symmetric trialkanolamines ligands is straight-
c
Yields in trialkanolamines after removal of the solvent, without further
purification.
forward (Scheme 1). They were synthesized very efficiently in one
step from bulky propylene oxides. Reactions of ammonia in
methanol with three equivalent of (S)-propylene oxide 1aed were
d
Determined via 1H NMR on the reaction mixture.
e
f
Isolated yields.
De of 2 were determined on the crude reaction product via 13C NMR. The
ꢀ
performed in closed autoclave reactors at 160 C in the present of
amount of diastereoselection observed depends on the enantiopurity of the reagent
activated 4 Å molecular sieves. Molecular sieves have been applied
with success organic synthesis because reaction rates can be greatly
increased by heating induced by molecular sieves [34e36].
1.
of Me
2
Zn and Ti(O-i-Pr)
4
. The addition reactions were carried out at
3
It is well known that the reaction between NH and (S)-pro-
ꢀ
0
C for 24 h. As can be seen 10 mol % of ligand with 2.0 equiv of
gave the propargylic al-
cohols in 80e83% yields but low enantioselectivity (Table 2, entries
e3) under the optimal reaction conditions. A promising result was
pylene oxide in a 1:3 stoichiometric ratio proceeded quantitatively
with the formation of (þ)-(S,S,S)-triisopropanolamine, together
with small quantities of the (þ)-(S,S,R) isomer arising from the
enantiomeric impurity of the propylene oxide [37]. Nucleophilic
attack of ammonia on the epoxides is a slow process and complete
dimethylzinc and 0.5 equiv of Ti(O-i-Pr)
4
1
obtained with ligand 2d, and the corresponding optically active
propargyl alcohol was obtained in 92% yield and 82% ee (Table 2,
entries 4). Interestingly, the enantioselectivity depended on the
conversion into the products can be obtained only after 4e6 days at
ꢀ
5
0e60 C. The reaction occurs with complete control of the
3
rigidity of R on the terminal of C -symmetric triisopropanolamine,
regiochemistry when alkyl epoxides are employed, while with aryl
epoxides (e.g. styrene oxide) the regioselectivity decreases signifi-
cantly and at least two of the four possible regioisomers are ob-
tained [38]. In present research, bulky aryl epoxides 1aed and
molecular sieves play important effect to obtain much higher
namely, the order was 9-fluorenyl < 9-ethylfluorenyl < 9-
propylfluorenyl < triphenylmethyl, which indicated that increase
in the bulkiness of the achiral end group (R) increased the enan-
tioselectivity of the reaction. The ee value of product increased with
increasing bulkiness of the end group R in the following order: 2a
3
regioselectivities in the synthesis of enantiopure C -symmetric
trialkanolamines.
(
(
9-fluorenyl) < 2b (9-ethylfluorenyl) < 2c (9-propylfluorenyl) < 2d
triphenylmethyl), i.e., there was a trend among ligands 2aed that
It is surprising that there were no the (þ)-(S,S,R) isomer arising
the catalytic enantioselectivity was higher with more sterically
hindered substituting group presence (Table 2, entries 1e4). Under
the optimal reaction conditions, ligand 2d was applied to the re-
action of phenylacetylene with a variety of aromatic and aliphatic
aldehydes. As the results summarized in Table 1 show, the chiral
propargyl alcohols could be obtained in good isolated yields of
from 1aed in the formation of (þ)-(S,S,S)-triisopropanolamine
2
aed whether or not molecular sieves were present (Table 1, en-
3
tries 1e5). The yield of C -symmetric ligand 2a slipped as low as
4
3% when molecular sieves was absent and in addition to 2a, two
other products derived from solvolysis of 1a were also largely
recovered: (R)-3-methoxy-1-(9-fluorenyl) arylpropanol 3a and (S)-
80e92% and excellent enantioselectivities of 80e95% ee for aro-
2
3
-methoxy-1-(9-fluorenyl) propanol 4a (55%, 35:20 ratio). C -
matic and aliphatic aldehydes (Table 2, entries 5e14). For para-
substituted benzaldehydes, the one with electron-donating group
gave a slightly higher enantioselectivity (Table 2, entries 6e7),
while the aldehydes with electron-withdrawing groups gave a little
symmetric ligands 2aed were obtained as a single regioisomer in
higher yields (82e90%) (Table 1, entries 2e5) in the presence of
molecular sieves. Therefore, notwithstanding the formation of
solvolysis products (3aed, 4aed), a quite significant improvement
in the regioselectivities (no (þ)-(S,S,R) isomer form) and yields of
lower enantioselectivities (Table 2, entries 8e9). a,b,-Unsaturated
trans-cinnamaldehyde afforded 82% enantioselectivity (Table 1,
entry 10). Aliphatic aldehydes such as nonanal and heptanal also
gave the products in good enantioselectivities of 82% and 80% ee,
respectively (Table 2, entries 4 and 11). Up to 95% ee can be
the desired C
also in this case.
The C -symmetric ligands 2aec were examined firstly in the
3
(þ)-(S,S,S)-triisopropanolamine 2aed were obtained
3
asymmetric addition of phenylacetylene to nonanal in the presence
Scheme 1. The synthesis of C
3
-symmetric trialkanolamines.

90
A.-L. Zhang et al. / Journal of Organometallic Chemistry 775 (2015) 88e93
Table 2
obtained with bulky 3,3,3-tribenylpropanal and naphthaldehyde
Table 2, entries 12e14). Moderate results were also observed with
a
Results for the addition of alkyne to aldehydes.
(
4-ethynyltoluene and cyclohexylacetylene (entries 15 and 16).
The general alkylation reaction protocol employs the achiral
precursor titanium tetra-isopropoxide [Ti(O-i-Pr) ] in the presence
4
of an enantiopure bidentate or tridentate ligand [39,40]. Under
such conditions, ligand exchange occurs in the coordination sphere
of the titanium nucleus [41,42], producing, among all the possible
complexes, a chiral, highly reactive species (ligand-accelerating
effect) which is responsible for the enantioselective outcome of the
process [43]. Due to the tendency of the Ti(IV) alkoxides to form
mixtures of oligomeric complexes equilibrating in solution and
because of the rapid ligand exchange equilibria [38,43,44], for the
majority of the processes cited above, the actual catalyst structure
remains elusive. In this work we present a detailed study focused
on the structural evaluation of the catalytic Ti(IV)/2d complexes,
Yield/%b
ee/%c
Entry
ReCHO
R
1
Ligand
1
2
3
4
5
6
7
8
9
Nonanal
Nonanal
Nonanal
Nonanal
Benzaldehyde
4-Methoxyphenzaldehyde
4-Tolualdehyde
4-Nitrobenzaldehyde
4-Chlorobenzaldehyde
Cinnamaldehyde
Heptanal
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-CH
2a
2b
2c
82
80
83
92
80
88
92
82
82
80
82
90
85
88
76
82
46
50
56
82
90
92
90
80
84
82
80
95
92
95
82
76
2d
2d
2d
2d
2d
2d
2d
2d
2d
2d
2d
2d
2d
10
11
12
13
14
15
16
1
Our approach employs standard H NMR analysis to assess the
3,3,3-Tribenylpropanal
nature of the various titanium species equilibrating in solution.
Ligand 2d bind tightly to the titanium center in a tetradentate
fashion, producing complexes whose nature depends on the stoi-
b
a
-Naphthaldehyde
-Naphthaldehyde
Benzaldehyde
Benzaldehyde
3
Ph
Cyclohexyl
4
chiometry of the reaction with Ti(O-i-Pr) (Scheme 2).
a
ꢀ
1
Toluene: 13 mL; RCHO: 1 mmol; reaction time: 24 h; reaction temperature: 0 C;
H NMR study of with the addition of Ti(O-i-Pr)
4
was conducted
1
n (RCHO)/n (ligand)/n (Ti(O-i-Pr)
4
)/Et
2
Zn ¼ 1/0.1/0.5/3.
and the selected H NMR spectra in the d 3.0 ppmed 5.0 ppm region
b
The isolated yield.
The ee of the product was determined by chiral HPLC.
are shown in Fig. 1. In Fig. 1a, I resonance belongs to the eOH, while
II and V resonances are relative to 5d. III and VI are respectively the
c
2
eCHeO methyne resonance and NCH e methylene resonance of
Scheme 2. Plausible stereochemical models for Ti-2d ligand.

A.-L. Zhang et al. / Journal of Organometallic Chemistry 775 (2015) 88e93
91
Fig. 1. 1H NMR titration of in situ-formed complex 5d (5 ꢃ 10ꢂ3 M) by 2d in deuteriochloroform at 0 C for 2d: Ti(IV) ratios (a) 3:1, (b) 2:1, (c) 1:1, (d) 1:2, (e) 1:3, (f) 1:5.
ꢀ
complexes (6d, 7d, 8d) formed by the coordination of Ti with other
coordinating group such as eNCH , eOCHCH , eO-i-Pr. IV belong to
the eCHeO methyne resonance of i-PrOH which is derived from
the coordination process of Ti(O-i-Pr) with 2d. When a precise 1:1
d/Ti(IV) ratio is employed, catalyst 5d is obtained (Scheme 2). At
4
by Elemental vario EL instrument. Ti(O-i-Pr) was freshly distilled
2
2
prior to use. Dimethylzinc (1.0 M solution in toluene) and aldehydes
were purchased from Aladdin Company and used directly. Re-
actions were monitored by thin layer chromatography (TLC).
4
2
the same time, a complex mixture of polynuclear Ti(IV)-based
species 6d, 7d and 8d also forms from the interaction of Ti(IV)
with equimolar quantities or a slight molar excess of ligand 2d
Synthesis of chiral ligands
A 20 mL autoclave with stirrer was charged with 1 mmol
substituted propylene epoxide (1aec), 0.3 mmol of NH $H O(mass
3 2
concentration:26%e28%), 1 g 4 Å molecular sieve and 10 mL of
methanol. The mixture was stirred at 160 C for 48 h. Methanol was
evaporated under reduced pressure. The residue was chromato-
graphed on silica gel using a mixture of petroleum ether and ethyl
acetate as eluate to obtain epoxy-opening products 2aed.
(
Fig. 1cea). It is surprised that the resonances of 5d are absent on
the basis of the NMR evidence reported in Fig. 1d. Namely, a total of
equiv of ligand Ti(O-i-Pr) versus 2d (Fig. 1d) causes the total
2
4
ꢀ
displacement of the apical isopropoxy ligand. It is preferred to
employ either equimolar quantities or up to 4 equiv excess of Ti(O-
i-Pr) because of the complete translation of 5d to polynuclear
4
Ti(IV)-based species (6d, 7d and 8d). Likely, the polyalcoholic na-
ture of the ligand can promote the formation of Ti(IV)-based olig-
omers which could play important roles in the asymmetric
alkynylation of aldehydes mentioned above.
(S,S,S)-Tri(3-(9-fluoren-9-yl)-2-propanol) amine 2a
ꢀ
20
ꢀ
Yield, 80%; m.p. ¼ 90 C ½aꢁ
¼ þ45 ; Elem. Anal. Calcd for
3
65
C
1
48
H
45NO
3
: C, 84.30; H, 6.63; N, 2.05; found C, 83.06; H, 6.93; N,
3
In summary, we have described new C -symmetric (S,S,S)-trii-
1
.95. H NMR (400 MHz, CDCl
3
)
d
7.80 (t, J ¼ 7.0 Hz, 6H, AreH), 7.68
sopropanolamine with high regioselectivity (up to 100%). which
could be prepared easily from bulky epoxides and ammonia in the
present of molecular sieves. The enantioselective addition of phe-
(
d, J ¼ 7.2 Hz, 3H, AreH), 7.54 (d, J ¼ 7.1 Hz, 3H, AreH), 7.40 (d,
J ¼ 4.0 Hz, 6H, AreH), 7.36e7.13 (m, 6H, AreH), 4.25 (s, 3H, CH), 3.97
13
(s, 3H, CH), 3.75 (m, 3H, CH
2 2
), 2.48e2.04 (m, 9H, CH ). C NMR
nylacetylene to aldehydes catalyzed by 2d/Ti(O-i-Pr)
4
was
(
100 MHz, CDCl 147.85, 146.95, 141.04, 140.74, 127.09, 125.27,
3
) d
demonstrated with excellent enantioselectivity (up to 95% ee). The
1
124.43, 119.95, 65.99, 61.54, 44.32, 38.85.
H NMR spectra support that there could be a complex mixture of
polynuclear Ti(IV)-based species form from the interaction of Ti(IV)
with ligand 2d. A further research about the actual catalyst struc-
tures of these ligand-Ti systems in this asymmetric addition is
currently under the way.
(
S)-3-Methoxy-1-(9-fluoren-9-yl)-2-propanol 3a
2
0
ꢀ
1
Yield, 15%; ½aꢁ
¼ þ35 ; H NMR (400 MHz, CDCl
3
) d 7.77 (t,
365
J ¼ 7.5 Hz, 1H, AreH), 7.66 (d, J ¼ 7.3 Hz, 1H, AreH), 7.52 (d,
J ¼ 7.3 Hz,1H, AreH), 7.44e7.21 (m, 5H, AreH), 4.23 (s, 1H, CH), 4.04
(
s, 1H, CH), 3.46 (dd, J ¼ 9.5, 7.1 Hz, 2H, CH ), 3.30 (d, J ¼ 2.8 Hz, 1H,
2
Experimental section
13
CH
100 MHz, CDCl
19.96, 75.01, 68.29, 66.72, 44.03, 36.90.
2
), 3.24e3.13 (m, 1H, CH
2
), 1.19 (t, J ¼ 7.0 Hz, 3H, CH
3
). C NMR
(
1
3
) d
147.70, 146.68, 141.09, 127.04, 125.35, 124.36,
General information
All the reactions were carried out under a dry nitrogen atmo-
sphere. Melting points were taken on an X-4 melting point appa-
(R)-2-Methoxy-3-(9-fluoren-9-yl)-1-propanol 4a
1
13
20
ꢀ
1
ratus and were uncorrected. H NMR and C NMR spectra were
taken on Bruck Avance 400 using CDCl as a solvent and tetrame-
Yield, 5%; ½aꢁ
¼ ꢂ52.6 ; H NMR (400 MHz, CDCl
3
) d 7.77 (t,
3
65
3
J ¼ 7.3 Hz, 2H, AreH), 7.65 (d, J ¼ 7.3 Hz, 1H, AreH), 7.52 (d,
thylsilane as an internal standard at 400 MHz and 100 MHz
respectively. Enantiomeric excess (ee) determination was carried
out by HPLC (Dionex P680) using a chiral OD-H column. Solvent:
hexane/isopropanol; Optical rotations were measured on a Perki-
nElmer 341 LC polarimeter. Elemental analyses were determined
J ¼ 6.7 Hz,1H, AreH), 7.44e7.23 (m, 4H, AreH), 4.22 (s,1H, CH), 4.03
(s, 1H, CH), 3.33 (s, 3H, CH
3
), 3.26 (d, J ¼ 9.3 Hz, 1H, CH
2
), 3.16 (d,
13
J ¼ 8.1 Hz, 1H, CH
147.65, 140.79, 127.03, 125.22, 124.29, 119.94, 76.86, 68.24, 61.28,
44.09, 36.88.
2 2 3
), 2.32 (s, 2H, CH ). C NMR (100 MHz, CDCl )
d

92
A.-L. Zhang et al. / Journal of Organometallic Chemistry 775 (2015) 88e93
(
S,S,S)-Tri(3-(9-ethylfluoren-9-yl)-2-propanol) amine 2b
NMR (100 MHz, CDCl
45.76, 30.36.
3
) d 147.15, 129.18, 126.18, 126.18, 70.12, 48.23,
ꢀ
20
ꢀ
Yield, 82%; m.p. ¼ 95 C ½aꢁ
¼ þ140 ; Elem. Anal. calcd for
3
65
C
1
54
H
57NO
3
: C, 84.45; H, 7.48; N, 1.82; found C, 83.56; H, 6.92; N,
1
.85. H NMR (400 MHz, CDCl
3
)
d
7.68 (t, J ¼ 7.5 Hz, 6H, AreH), 7.30
(S)-3-Methoxy-1-triphenylmethyl-2-propanol 3d
2
3
0
ꢀ
1
(
(
6
d
dt, J ¼ 20.1, 6.9 Hz, 15H, AreH), 7.15 (d, J ¼ 7.3 Hz, 3H, AreH), 2.71
s, 3H, CH), 2.25e1.78 (m, 9H, CH ), 1.70e1.60 (m, 3H, CH ), 1.25 (m,
). C NMR (100 MHz, CDCl
Yield, 5%; ½aꢁ
¼ ꢂ43.5 ; H NMR (400 MHz, CDCl
3
) d 7.37 (d,
65
2
2
J ¼ 7.7 Hz, 5H), 7.32e7.24 (m, 8H), 7.20 (d, J ¼ 7.2 Hz, 8H), 3.75 (s,1H,
CH), 3.27 (d, J ¼ 6.8 Hz, 1H, CH ), 3.10e2.88 (m, 1H, CH ), 2.62e2.36
(m, 2H, CH ). C NMR (100 MHz, CDCl
147.09, 129.20, 128.20, 128.00, 126.11, 68.00, 60.06, 58.06, 44.31,
0.02.
13
H, CH
2
), 0.31e0.08 (m, 9H, CH
3
3
)
2
2
13
149.78, 149.08, 140.88, 127.20, 123.70, 123.08, 119.92, 65.15, 60.92,
3.84, 44.40, 33.47, 8.07.
2
), 1.09 (t, J ¼ 7.0 Hz, 3H, CH
3
3
)
5
d
3
(
S)-3-Methoxy-1-(9-ethylfluoren-9-yl)-2-propanol 3b
20
ꢀ
1
(
R)-2-Methoxy-3-triphenylmethyl-2-propanol 4d
Yield, 10%; ½aꢁ3
¼ þ52.6 ; H NMR (400 MHz, CDCl
3
)
65
2
0
ꢀ
1
Yield, 4%; ½aꢁ
¼ þ37.8 ; H NMR (400 MHz, CDCl
3
)
d
7.37 (d,
J ¼ 7.6 Hz, 5H, AreH), 7.32e7.21 (m, 6H, AreH), 7.19 (t, J ¼ 7.1 Hz, 4H,
AreH), 3.76 (s, 1H, CH), 3.16 (s, 3H, CH ), 3.04e2.86 (m, 2H), 2.58
ddd, J ¼ 13.1, 12.2, 4.1 Hz, 2H). C NMR (100 MHz, CDCl 147.09,
29.21, 128.03, 128.00, 126.12, 68.01, 60.02, 59.06, 45.31, 45.02.
d
7.84e7.71 (m, 2H, AreH), 7.51 (d, J ¼ 6.6 Hz, 2H, AreH), 7.46e7.34
365
(
2
2
m, 4H, AreH), 3.14 (s, 3H, CH
3
), 2.86 (dd, J ¼ 9.8, 6.4 Hz, 2H, CH
.37 (dd, J ¼ 14.2, 6.6 Hz, 1H, CH), 2.28 (dd, J ¼ 14.2, 4.7 Hz, 1H, CH
.19e1.97 (m, 2H, CH
2
2
),
),
3
13
(
1
3
) d
2
), 1.57 (d, J ¼ 2.6 Hz, 1H, CH
2
), 0.33 (t,
3 3
). C NMR (100 MHz, CDCl ) d 149.30, 149.05,
1
3
J ¼ 7.3 Hz, 3H, CH
1
41.11, 127.35, 123.52, 123.10, 120.05, 76.77, 67.71, 58.70, 53.90,
General procedure for asymmetric addition of phenylacetylene to
aldehydes
4
3.26, 33.83, 8.02.
(
R)-2-Methoxy-3-(9-ethylfluoren-9-yl)-1-propanol 4b
20
ꢀ
1
Under dry nitrogen, the ligand (0.1 mmol) and Ti-(O-i-Pr)4
0.5 mmol) were mixed in the solvent (13 mL) at room temperature.
Then dimethylzinc (3 mL, 1.0 M solution in toluene) was added.
After the mixture was stirred at room temperature for 2 h, phe-
Yield, 8%; ½aꢁ3 ¼ ꢂ64.8 ; H NMR (400 MHz, CDCl
3
)
d
7.72 (d,
J ¼ 7.1 Hz, 1H, AreH), 7.42 (d, J ¼ 8.0 Hz, 1H, AreH), 7.39e7.30 (m,
H, AreH), 7.26 (s, 3H, AreH), 2.99 (s, 1H, CH), 2.91 (s, 1H, CH ), 2.77
s, 3H, CH
), 2.36 (dd, J ¼ 19.2, 6.0 Hz, 1H), 2.28e2.16 (m, 1H), 2.04
dd, J ¼ 7.3, 2.9 Hz, 1H), 0.29 (t, J ¼ 7.3 Hz, 2H). C NMR (100 MHz,
149.14, 141.23, 127.23, 123.55, 123.07, 119.89, 78.79, 64.77,
6.71, 53.78, 40.85, 33.82, 8.14.
65
(
3
(
(
2
3
13
nylacetylene (3 mmol) was added and the mixture was stirred for
ꢀ
1
h. Then the reaction solution was cooled to 0 C, the solution of
3
CDCl ) d
5
aldehyde (1 mmol) in dry toluene (2 mL) was added. After the re-
action was completed (TLC), and quenched by 5% aqueous HCl. The
mixture was extracted with diethyl ether (3x10 mL). The extract
(
S,S,S)-Tri(3-(9-propylfluoren-9-yl)-2-propanol) amine 2c
20
ꢀ
was washed with brine (3 ꢃ 15 mL), dried over anhydrous Na
2 4
SO ,
ꢀ
Yield, 92%; m.p. ¼ 98 C ½aꢁ
¼ þ73.5 ; Elem. Anal. calcd for
3
65
and concentrated under vacuum. The crude product was purified
by flash column chromatography (silica gel,15% EtOAc in petroleum
ether) to give the propargyl alcohol.
C
57 3
H63NO : C, 84.51; H, 7.84; N,1.73; found C, 85.55; H, 7.62; N,1.55.
1
H NMR (400 MHz, CDCl
5H, AreH), 7.16 (d, J ¼ 7.4 Hz, 6H, AreH), 2.68 (d, J ¼ 4.5 Hz, 3H,
CH), 2.13e1.94 (m, 3H, CH ), 1.95e1.71 (m, 6H, CH ), 1.22 (dt,
J ¼ 13.3, 11.6 Hz, 6H), 0.95e0.77 (m, 3H, CH ), 0.62 (t, J ¼ 6.9 Hz, 6H,
). C NMR (100 MHz, CDCl 150.35,
49.64, 140.82, 127.81, 123.79, 123.16, 119.97, 65.27, 61.23, 53.57,
4.76, 43.23, 16.99, 14.49.
3
)
d
7.68 (t, J ¼ 7.4 Hz, 3H, AreH), 7.29 (m,
1
2
2
Acknowledgments
2
13
CH
1
4
2
), 0.56e0.37 (m, 9H, CH
3
3
) d
We are grateful to the National Natural Science Foundation of
China (No. 21172186) and Doctor Student Research Foundation of
Chinese Education Ministry (No. 20134301110004) for generous
financial support for our programs.
(
S)-3-Methoxy-1-(9-propylfluoren-9-yl)-2- propanol 3c
2
0
ꢀ
1
Yield,6%; ½aꢁ3 ¼ þ63.4 H NMR (400 MHz, CDCl
3
)
d
7.79e7.64
65
Appendix A. Supplementary data
(
m, 2H, AreH), 7.47 (d, J ¼ 6.7 Hz, 1H, AreH), 7.32 (m, 5H, AreH),
3
1
1
.09 (s, 3H, CH
H, CH), 2.22 (dd, J ¼ 14.3, 4.7 Hz, 1H, CH
H), 1.50 (d, J ¼ 2.9 Hz, 1H, CH ), 0.74e0.53 (m, 5H, Et). C NMR
149.11, 140.81, 127.18, 123.49, 123.01, 119.87,
8.63, 64.77, 56.65, 53.42, 43.50, 41.01, 16.91, 14.33.
3
), 2.90e2.67 (m, 2H, CH
2
), 2.32 (dd, J ¼ 14.3, 6.6 Hz,
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2014.10.027.
2
), 1.99 (dt, J ¼ 15.5, 8.1 Hz,
13
2
(
3
100 MHz, CDCl ) d
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20
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