Asymmetric addition of phenylacetylene to aldehydes catalyzed by complex of O-sulfonyl camphor derivatives and titanium

Article abstract of DOI:10.1002/aoc.3423

Several novel ligands that are based on the camphor skeleton or contain the O-sulfonyl group were synthesized and used in the asymmetric addition of phenylacetylene to aldehydes. This enantioselective reaction afforded chiral propargylic alcohols in high

Full text of DOI:10.1002/aoc.3423

Full paper
Received: 1 September 2015
Revised: 22 November 2015
Accepted: 29 November 2015
Published online in Wiley Online Library: 26 January 2016
(wileyonlinelibrary.com) DOI 10.1002/aoc.3423
Asymmetric addition of phenylacetylene to
aldehydes catalyzed by complex of O-sulfonyl
camphor derivatives and titanium
Dong-Sheng Lee*, Chang-Weu Gau, Yu-Yang Chen and Ta-Jung Lu
Several novel ligands that are based on the camphor skeleton or contain the O-sulfonyl group were synthesized and used
in the asymmetric addition of phenylacetylene to aldehydes. This enantioselective reaction afforded chiral propargylic
alcohols in high yields and with good to excellent levels of enantiopurity (up to 99% enantiomeric excess). Copyright ©
2016 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: asymmetric alkynylation; O-sulfonyl ligand; propargylic alcohol; titanium catalysis
esterification of salicyladehyde with sulfonyl chloride.[11a] The ab-
solute configuration of 3c was confirmed as (1R,2S,3R,4S) using
Introduction
Efficient methods for the preparation of optically active propargylic
alcohols are of particular interest because of the significance of
these intermediates in the manufacturing of pharmaceuticals.
For instance, (ꢀ)-virginiamycin M2,[1] adociacetylene B[2] and
asteriscunolide D[3] (Fig. 1) are all physiologically active compounds.
Additionally, optically active propargylic alcohols are precursors for
many chiral materials such as optically active allenes and
vinylsilanes.[4]
single-crystal X-ray diffraction (Fig. 2).[11b]
The addition of phenylacetylene to benzaldehyde (5a) catalyzed
with ligands 3a–3f and Ti(OiPr)4 was firstly studied to investigate
the optimal reaction conditions. Various reaction parameters, such
as ligand loading, amount of titanium, solvent and temperature,
were examined (Table 1). The ortho-substituted ligand 3b exhibits
a slightly greater reaction activity and enantioselectivity than ligand
3a (entries 1 and 2). The enantioselectivity slightly increases as the
ratio of ligand to Ti(OiPr)4 decreases from 1:3 to 1:2 (entry 3). n-
Hexane is the best solvent in this reaction (entry 4, 51% ee). To
improve the enantioselectivity of this reaction, O-sulfonyl ligands
3c–3f were synthesized and utilized in the asymmetric addition. Ex-
perimental results reveal that the ee value is thus significantly im-
proved to 73% (entries 9 and 10). A low reaction temperature
(ꢀ20°C) increases ee further from 73 to 85% (entry 12 versus 10).
Ligand 3d provides better enantioselectivity than ligands 3e and
3f in the asymmetric addition of phenylacetylene to benzaldehyde
(entries 12–14), indicating that the camphor backbone is crucial for
high enantioselectivity. The alkynylation product 6a favors the (R)
configuration based on comparison with reported optical rotation
values.[12]
The enantioselective alkynylation of aldehydes is one of the most
effective methods for preparing optically active propargylic
alcohols.[5] Several chiral ligands, such as 1,1′-bi-2-naphthol
derivatives,[6] amino alcohols,[7] oxazolines,[8] (ꢀ)-2-exo-morpho-
linoisobornane-10-thiol[9] and imino alcohols,[10] have been used
in the enantioselective addition of alkynes to aldehydes. In 2004,
Wang and co-workers[7c] reported the asymmetric addition of
phenylacetylene to aldehydes using a camphorsulfonamide tita-
nium complex as a catalyst. The reactions were performed at room
temperature for 12 h in the presence of 10 mol% of
camphorsulfonamide and gave the products with high yields and
high enantiomeric excess (ee). However, diethylzinc (3.0 equiv.)
and phenylacetylene (3.0 equiv.) were used and the reaction time
was long (12 h). To the best of our knowledge, ligands that contain
the O-sulfonyl group have not yet been examined in this context.
Therefore, in the work reported here, an effective and stable chiral
catalyst system was developed for catalyzing the addition of al-
kynes to aldehydes. New classes of camphor-based ligands that
bear the O-sulfonyl moiety, and their application to the catalytic
asymmetric alkynylation of aldehydes, are presented.
The scope of the alkynylation reaction was then examined using
various aldehydes 5 and phenylacetylene (Table 2). Ortho-
substituted benzaldehyde exhibits slightly higher enantioselectivity
than meta and para substitutions (entries 2–4). Furthermore,
all other ortho-substituted aromatic aldehydes react with
phenylacetylene to produce propargylic alcohols 6 with good
enantioselectivities (86–92% ee) and excellent yields (87–96%). In
Results and discussion
*
Correspondence to: Dong-Sheng Lee, Department of Chemistry, National
Chung-Hsing University, Taichung, 40227, Taiwan. E-mail: dslee@mail.nchu.edu.tw
A series of ligands 3 can be obtained from salicylaldehyde or its de-
rivatives 1 and corresponding amino alcohols 2 with good yields
(63–92%; Scheme 1). Derivatives 1 were prepared easily via the
Department of Chemistry, National Chung-Hsing University, Taichung, 40227,
Taiwan
Appl. Organometal. Chem. 2016, 30, 242–246
Copyright © 2016 John Wiley & Sons, Ltd.

Asymmetric alkynylation of phenylacetylene to aldehydes
Table 1. Alkynylation of benzaldehyde with phenylacetylene in the
presence of ligands 3a–fa
Entry Ligand
(equiv.)
Ti(OiPr)4
(equiv.)
Solvent
Temp. Yield ee (%)b
(°C)
(%)
1
3a (0.20)
3b (0.20)
3b (0.20)
3b (0.20)
3b (0.20)
3b (0.20)
3b (0.10)
3b (0.30)
3c (0.20)
3d (0.20)
3d (0.20)
3d (0.20)
3e (0.20)
3f (0.20)
0.60
0.60
0.40
0.40
0.40
Toluene
Toluene
Toluene
n-Hexane
CH2Cl2
25
90
93
90
88
90
43
9
40 (R)
46 (S)
48 (S)
51 (S)
48 (S)
41 (S)
16 (S)
48 (S)
73 (R)
73 (R)
80 (R)
85 (R)
7 (S)
2
25
25
3
Figure 1. Examples of manufactured pharmaceuticals.
4
25
5
25
6
0.40 Tetrahydrofuran
25
7
0.20
0.60
0.40
0.40
0.40
0.40
0.40
0.40
n-Hexane
n-Hexane
n-Hexane
n-Hexane
n-Hexane
n-Hexane
n-Hexane
n-Hexane
25
8
25
93
90
90
92
87
33
53
9
25
10
11c
12d
13
14
25
0
ꢀ20
ꢀ20
ꢀ20
13 (R)
aAll reactions performed at 25 °C for 3 h.
bValues of ee obtained using HPLC with a chiral OD-H column.
cReaction performed at 0 °C over 5 h.
dReaction performed at ꢀ20 °C over 5 h.
particular, 4-anisaldehyde yields the chiral alcohol 6j with the
highest enantioselectivity (99%; entry 10). Heteroaromatic alde-
hydes result in high ee values, as can be seen for substrates thio-
phene and furan (entries 11 and 12). Aliphatic aldehydes also give
propargylic alcohols with good ee values in excellent yields (entries
13 and 14).
Conclusions
Several novel ligands based on the camphor skeleton or containing
sulfonyl moieties were easily developed, and applied to the
enantioselective addition of phenylacetylene to aldehydes. This
catalytic reaction is completed within a short reaction time (5h) at
ꢀ20 °C. Two equivalent amounts of dimethylzinc and acetylene
were used in the catalytic system. A promising system for the prep-
aration of chiral propargylic alcohols in high yield and good to ex-
cellent ee (up to 99%) was thus established. The properties of the
O-sulfonyl moiety in the ligands with respect to the titanium-
catalyzed asymmetric alkynylation reaction were elucidated for
the first time. Further study of the use of these ligands in other
asymmetric reactions is ongoing. The catalyst system is suitable
for use in the preparation of pharmaceutically important molecules
and natural products.
Scheme 1. Synthesis of novel camphor-based ligands and amino alcohol
ligands 3.
Experimental
Materials and methods
Reactions were analyzed using pre-coated silica gel 60 (F-254)
Figure 2. X-ray crystal structure of 3c.
plates (0.2mm layer thickness), using a solution of 0.5%
Appl. Organometal. Chem. 2016, 30, 242–246
Copyright © 2016 John Wiley & Sons, Ltd.
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D.-S. Lee et al.
Table 2. Alkynylation of phenylacetylene with aldehydes 5 catalyzed by 3d
Entry
R
Product
Yield (%)a
ee (%)b
Entry
R
Product
Yield (%)a
ee (%)b
1
2
3
4
5
6
7
Ph
6a
6b
6c
90
87
90
88
96
89
96
85 (R)
90 (R)
86 (R)
86 (R)
86 (R)
86 (R)
88 (R)
8
9
o-BrC6H4
6 h
6i
(91)
(91)
(92)
(93)
(95)
(93)
(91)
92 (R)
88 (R)
99 (R)
92 (R)
82 (R)
88 (R)
86 (R)
o-MeC6H4
m-MeC6H4
p-MeC6H4
o-MeOC6H4
o-FC6H4
1-Naphthyl
p-MeOC6H4
2-Thiophenyl
Furanyl
10
11
12c
13
14
6j
6d
6e
6f
6 k
6 l
Cyclohexyl
t-Butyl
6 m
6n
o-ClC6H4
6 g
aIsolated yield.
bValues of ee were determined using HPLC with a chiral OD-H column.
cReaction performed at ꢀ20 °C over 10 h.
phosphomolybdic acid in 95% ethanol as the detector. All products
were purified by column chromatography (silica gel, 0.040–
0.063 mm) using hexane–ethyl acetate as eluent unless otherwise
indicated. Melting points were determined using a Mel-Temp
1001D (Barnstead/Thermo) digital melting point apparatus and
were uncorrected. Optical rotations were recorded with an
Autopol® IV automatic polarimeter (Rudolph Research Analytical)
using a 1.0dm cell at specific temperatures. 1H NMR and 13C NMR
spectra were recorded using a Varian Mercury 400 spectrometer
in CDCl3 with chemical shifts (δ) recorded relative to
tetramethylsilane. The central peak of CDCl3 (δ = 77.0 ppm) was
used as internal standard for 13C NMR spectra. High-resolution mass
spectra (HRMS) were recorded using a Finnigan/Thermo Quest MAT
95XL mass spectrometer. Mass spectra were obtained using either
the electron impact (EI) or electrospray ionization method. Enantio-
meric excess of secondary alcohols was determined using HPLC
with chiral columns, using a mixture of isopropanol and n-hexane
as the mobile phase.
6.77 (t, J = 7.6Hz, 1H, C14-H), 4.00 (d, J = 13.6 Hz, 1H, C11-H, NCH2Ph),
3.94 (d, J = 13.6 Hz, 1H, C11-H, NCH2Ph), 3.77 (d, J = 7.6Hz, 1H, C2-H,
CHOH), 2.79 (d, J = 7.6 Hz, 1H, C3-H, NCH), 1.78 (d, J= 4.4Hz, 1H,
C4-H, CH), 1.72–1.65 (m, 1H, C5-H, CH2), 1.51–1.45 (m, 1H, C6-H,
CH2), 1.15 (s, 3H, C10-H, CH3), 1.03–0.95 (m, 2H, C5-H and C5-H,
CH2), 0.93 (s, 3H, C8-H, CH3), 0.81 (s, 3H, C9-H, CH3). 13C NMR (CDCl3,
100 MHz, δ, ppm): 158.1 (C17), 128.7 (C13), 128.3 (C15), 123.3 (C12),
118.9 (C14), 116.3 (C16), 80.1 (C2, OCH), 66.1 (C3, NCH), 53.1 (C4, CH),
50.1 (C1, CCH3), 49.1 (C7, CMe2), 46.7 (C11, NCH2), 33.1 (C6, CH2),
26.7 (C5, CH2), 21.7 (C8, CH3), 21.0 (C9, CH3), 11.3 (C10, CH3). HRMS-
EI (m/z) [M]+ Calcd for C17H25NO2: 275.1885; found: 275.1877. Anal.
Calcd for C17H25NO2 (%): C, 74.14; H, 9.15; N, 5.09; found (%): C,
73.59; H, 9.35; N, 4.86.
(1R,2S,3R,4S)-3-[(2-hydroxy-3-tert-butylbenzyl)amino]-2-hydroxy-1,7,7-trimethyl-
bicyclo[2.2.1]heptane (3b)
25
Yield 85% (0.845 g); white solid; ½αꢁD = +28.5 (c = 1.00, CHCl3); m.p.
118–119 °C. 1H NMR (CDCl3, 400 MHz, δ, ppm): 7.19 (dd, J= 7.6,
1.2 Hz, 1H, C15-H), 6.88 (d, J= 7.6 Hz, 1H, C13-H), 6.71 (t, J= 7.6 Hz,
1H, C14-H), 4.04 (d, J= 13.6 Hz, 1H, C11-H, NCH2Ph), 3.90 (d,
J= 13.6 Hz, 1H, C11-H, NCH2Ph), 3.76 (d, J= 7.6 Hz, 1H, C2-H, CHOH),
2.77 (d, J= 7.6 Hz, 1H, C3-H, NCH), 1.75 (d, J= 4.4 Hz, 1H, C4-H, CH),
1.69–1.61 (m, 1H, C5-H, CH2), 1.50–1.44 (m, 1H, C6-H, CH2), 1.42 (s,
9H, C(CH3)3), 1.15 (s, 3H, C10-H, CH3), 1.02–0.96 (m, 2H, C5-H and C5-
H, CH2), 0.93 (s, 3H, C8-H, CH3), 0.80 (s, 3, C9-H, CH3). 13C NMR (CDCl3,
100 MHz, δ, ppm): 157.2 (C17), 136.7 (C12), 126.5 (C13), 125.8 (C15),
123.6 (C16), 118.1 (C14), 80.1 (C2, OCH), 66.2 (C3, NCH), 53.6 (C4, CH),
49.9 (C1, CMe), 49.0 (C7, CMe2), 46.7 (C11, NCH2), 34.6 (C18, CMe3),
33.2 (C6, CH2), 29.5 (C(CH3)3), 26.6 (C5, CH2), 21.7 (C8, CH3), 21.0 (C9,
CH3), 11.3 (C10, CH3). HRMS-EI (m/z) [M]+ Calcd for C21H33NO2:
331.2511; found: 331.2504. Anal. Calcd for C21H33NO2(%): C, 76.09;
H, 10.03; N, 4.23; found (%): C, 76.10; H, 9.83; N, 4.03.
Compounds 1 were synthesized according to similar literature
procedures.[11a]
General procedure for preparation of ligands 3
Salicylaldehyde or derivative (3.00 mmol) in dry toluene (3ml) was
added to a solution of amino alcohol (3.90 mmol) in toluene (7ml)
and stirred in the presence of anhydrous Na2SO4 (6.00mmol) at
room temperature and then refluxed for 12 h. Then, it was filtered
through an anhydrous Na2SO4 plug and the filtrate was evaporated
to afford a Schiff base. The Schiff base was dissolved in methanol
(10 ml) and NaBH4 (6.00 mmol) was added. After stirring for 1 h,
methanol was removed and the residue was extracted using EtOAc
(3× 10 ml) and dried over Na2SO4. The liquid was filtered and sol-
vent removed to afford the product that was purified using chro-
matography (ethyl acetate–n-hexane= 1:15–1:5) to give ligand 3.
(1R,2S,3R,4S)-3-[(2-benzenesulfonylbenzyl)amino]-2-hydroxy-1,7,7-trimethylbicyclo
[2.2.1]heptane (3c)
(1R,2S,3R,4S)-3-[(2-hydroxybenzyl)amino)]-2-hydroxy-1,7,7-trimethylbicyclo[2.2.1]
heptane (3a)
Yield 63% (0.785 g); white solid; ½αꢁ2D4:0 = +27.3 (c = 1.22, CHCl3); m.p.
62–64 °C. 1H NMR (CDCl3, 400MHz, δ, ppm): 7.91 (dd, J = 8.4, 1.2Hz,
2H, C19-H and C23-H), 7.72 (tt, J= 8.4, 1.2Hz, 1H, C21-H), 7.58, (t,
J = 8.4Hz, 2H, C20-H and C22-H), 7.40 (dd, J = 7.6, 1.6Hz, 1H, C13-H),
7.25 (td, J = 7.6 Hz, 1.2 Hz, 1H, C15-H), 7.19 (td, J = 7.6 Hz, 1.6 Hz, 1H,
25
Yield 72% (0.599g); white solid; ½αꢁD = +24.9 (c = 1.00, CHCl3); m.p.
1
91–94 °C. H NMR (CDCl3, 400 MHz, δ, ppm): 7.16 (t, J = 7.6Hz, 1H,
C15-H), 7.00 (d, J= 7.6Hz, 1H, C13-H), 6.83 (d, J = 7.6 Hz, 1H, C16-H),
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Asymmetric alkynylation of phenylacetylene to aldehydes
C14-H), 6.89 (dd, J =7.6, 1.2Hz, 1H, C16-H), 3.79 (d, J = 13.6 Hz, 1H,
C11-H, NCH2Ph), 3.55 (d, J = 13.6 Hz, 1H, C11-H, NCH2Ph), 3.41 (d,
J =7.6 Hz, 1H, C2-H, CHOH), 2.70 (d, J = 7.6Hz, 1H, C3-H, NCH),
1.70–1.64 (m, 1H, C5-H, CH2), 1.55 (d, J = 4.8Hz, 1H, C4-H, CH),
1.43–1.38 (m, 1H, C6-H, CH2), 1.01 (s, 3H, C10-H, CH3), 0.98 (d,
J =8.4 Hz, 2H, C5-H and C6-H, CH2), 0.93 (s, 3H, C8-H, CH3), 0.75 (s,
3H, C9-H, CH3). 13C NMR (CDCl3, 100MHz, δ, ppm): 147.8 (C17),
135.8 (C18), 134.4 (C21), 133.4 (C12), 130.7 (C13), 129.3 (C20 and C22),
128.4 (C19 and C23), 128.3 (C15), 127.4 (C14), 122.2 (C16), 78.7 (C2,
OCH), 65.7 (C3, NCH), 51.4 (C4, CH), 48.9 (C1, CMe), 48.8 (C7, CMe2),
46.6 (C11, NCH2), 32.9 (C6, CH2), 27.1 (C5, CH2), 21.9 (C8, CH3), 21.2
(C9, CH3), 11.3 (C10, CH3). HRMS-EI (m/z) [M]+ Calcd for C23H29NO4S:
415.1823; found: 415.1820. Anal. Calcd for C23H29NO4S (%): C, 66.48;
H, 7.03; N, 3.37; found (%): C, 66.50; H, 7.19; N, 3.19.
H and C21-H), 7.38–7.28 (m, 6H, C4-H, C5-H, C6-H, C7-H, C8-H, and C11-
H), 7.24–7.17 (m, 4H, C12-H, C13-H, C18-H, and C20-H), 6.98 (dd, J = 7.6,
1.6 Hz, 1H, C14-H), 3.74–3.65 (m, 2H, C1-H, CH2OH), 3.55–2.49 (m, 2H,
C2-H and C9-H, NHCHPh and NCH2Ph), 3.40 (d, J = 13.6 Hz, 1H, C9-H,
NCH2Ph), 2.41 (s, 3H, C22-H, CH3), 2.00 (br, 2H, NH and OH). 13C NMR
(CDCl3, 100 MHz, δ, ppm): 147.8 (C15), 145.4 (C19), 140.2 (C3), 133.4
(C10), 132.7 (C16), 130.9 (C11), 129.8 (C18 and C20), 128.7 (C17 and
C21), 128.31 (C5 and C7), 128.27 (C13), 127.7 (C12), 127.3 (C4 and C8),
127.2 (C6), 122.4 (C14), 66.7 (C1, OCH2), 66.4 (C2, NCH), 45.7 (C9,
NCH2), 21.7 (C22, CH3). HRMS-EI (m/z) for C22H23NO4S calcd
397.1312 (M+); found 397.1314. Anal. Calcd for C22H23NO4S (%): N,
3.52; C, 66.48; H, 5.83; O, 16.10; found (%): N, 3.60; C, 66.40; H,
5.89; O, 15.99.
(1R,2S,3R,4S)-3-[(2-p-tolylsulfonylbenzyl)amino]-2-hydroxy-1,7,7-trimethylbicyclo
[2.2.1]heptane (3d)
General procedure for addition of phenylacetylene to
aldehydes
25:8
Yield 78% (1.01 g); white solid; ½αꢁD = +33.6 (c = 1.25, CHCl3); m.p.
All reactions were carried out under nitrogen using dried and
degassed solvent. Ligand 3 (0.100mmol) and Ti(OiPr)4 (60.0μl,
0.200mmol) were mixed in dry n-hexane (1.15ml) at room temper-
ature for 1 h. Then, a solution of ZnMe2 (0.85 ml, 1.2 M in toluene)
was added. After the mixture was stirred at room temperature for
1 h, phenylacetylene (110μl, 1.00 mmol) was added and stirred
for 1 h. The solution was cooled to ꢀ20 °C, and aldehyde 5
(0.500 mmol) was added. The resulting mixture was allowed to stir
for 5–10 h. After the reaction completed, checked using TLC, it
was quenched by NH4Cl (aq.). The aqueous layer was extracted with
EtOAc. The combined organic layers were washed with brine, dried
over Na2SO4 and concentrated under vacuum. The residue was pu-
rified by flash column chromatography (silica gel, 10% EtOAc in
hexane) to give product 6. The ee values of all propargylic
alcohols were determined using chiral HPLC (conditions for all
propargylic alcohols: Chiralcel OD-H, 10% 2-propanol–n-hexane,
1 ml minꢀ1, 254 nm; except 1-(2-bromophenyl)-3-phenylprop-2-
yn-1-ol: 0.25mlminꢀ1).
72–74 °C. 1H NMR (CDCl3, 400 MHz, δ, ppm): 7.78 (d, J = 8.4 Hz, 2H,
C19-H and C23-H), 7.40 (dd, J = 7.6, 1.6Hz, 1H, C13-H), 7.35, (d,
J =8.4 Hz, 2H, C20-H and C22-H), 7.24 (td, J = 7.6, 1.6Hz, 1H, C15-H),
7.19 (td, J = 7.6, 1.6 Hz, 1H, C14-H), 6.90 (dd, J = 7.6Hz, 1.6 Hz, 1H,
C16-H), 3.79 (d, J = 14.0 Hz, 1H, C11-H, NCH2Ph), 3.55 (d, J = 14.0 Hz,
1H, C11-H, NCH2Ph), 3.40 (d, J = 7.6Hz, 1H, C2-H, CHOH), 2.77 (d,
J =7.6 Hz, 1H, C3-H, NCH), 2.47 (s, 3H, C24-H, CH3), 1.69–1.64 (m,
1H, C5-H, CH2), 1.54 (d, J = 4.8Hz, 1H, C4-H, CH), 1.43–1.38 (m, 1H,
C6-H, CH2), 1.01 (s, 3H, C10-H, CH3), 0.97 (d, J = 8.4 Hz, C5-H and C6-
H, 2H), 0.97 (s, 3H, C8-H, CH3), 0.75 (s, 3H, C9-H, CH3). 13C NMR (CDCl3,
100 MHz, δ, ppm): 147.9 (C17), 145.6 (C21), 133.3 (C12), 132.8 (C18),
130.7 (C13), 129.9 (C20 and C22), 128.4 (C19 and C23), 128.3 (C15),
127.3 (C14), 122.2 (C16), 78.7 (C2, OCH), 65.7 (C3, NCH), 51.4 (C4, CH),
49.0 (C1, CMe), 48.8 (C7, CMe2), 46.6 (C11, NCH2), 32.9 (C6, CH2), 27.1
(C5, CH2), 21.9 (C8, CH3), 21.7 (C24, CH3), 21.2 (C9, CH3), 11.3 (C10,
CH3). HRMS-EI (m/z) [M]+ Calcd for C24H31NO4S: 429.1960; found:
429.1967. Anal. Calcd for C24H31NO4S (%): C, 67.10; H, 7.27; N, 3.26;
found (%): C, 67.23; H, 7.55; N, 3.20.
(S)-2-(((1-hydroxy-3-methylbutan-2-yl)amino)methyl)phenyl-4-methylbenzene-
sulfonate (3e)
Acknowledgements
We thank the National Science Council of the Republic of China for
financial support under grant no. 102WFA0500216. Ted Knoy is ap-
preciated for his editorial assistance.
24:2
Yield 82% (1.50 g); colorless liquid; ½αꢁD = +94.0 (c = 1.0, CHCl3). 1H
NMR (CDCl3, 400 MHz, δ, ppm): 7.74 (d, J =8.0 Hz, 2H, C14-H and C18-
H), 7.42 (d, J = 7.6Hz, 1H, C8-H), 7.33 (d, J = 8.0Hz, 2H, C15-H and C17-
H), 7.22 (t, J= 8.0Hz, 1H, C10-H), 7.16 (t, J = 7.6Hz, 1H, C9-H), 6.88 (d,
J =8.0 Hz, 1H, C11-H), 3.73 (d, J = 13.6 Hz, 1H, C6-H, NCH2), 3.59 (d,
J = 10.8 Hz, 1H, C1-H, CH2OH), 3.55 (d, J = 13.6 Hz, 1H, C6-H, NCH2),
3.33 (d, J = 10.8 Hz, 1H, C1-H, CH2OH), 2.45 (s, 3H, C19-H, CH3), 2.39–
2.33 (m, 1H, C2-H, NCH), 2.35 (br, 2H, NH and OH), 1.85–1.73 (m,
1H, C3-H, NCHMe2), 0.93 (d, J = 6.8Hz, 3H, C4-H, CH3), 0.87 (d,
J =6.8 Hz, 3H, C5-H, CH3). 13C NMR (CDCl3, 100 MHz, δ, ppm): 147.9
(C12), 145.6 (C16), 133.4 (C7), 132.8 (C13), 130.9 (C8), 129.9 (C15 and
C17), 128.42 (C14 and C18), 128.40 (C10), 127.4 (C9), 122.2 (C11), 64.4
(C1, OCH2), 60.2 (C2, NCH), 45.6 (C6, NCH2), 28.8 (C3, CMe2), 21.7
(C19, CH3), 19.5 (C4, CH3), 18.4 (C5, CH3). HRMS-ESI (m/z) for
C19H26NO4S calcd 364.1577 (M + H+); found 364.1574. Anal. Calcd
for C19H25NO4S (%): N, 3.85; C, 62.78; H, 6.93; O, 17.61; found (%):
N, 3.60; C, 59.88; H, 6.72; O, 17.61.
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Appl. Organometal. Chem. 2016, 30, 242–246