P. N. Kalaria et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
5
Table 4 (continued)
Entry
a
,b-Unsaturated carbonyl compounds
Thiols
Product
Time (h)
Yield (%)b
ee (%)c
SH
O
O
*
O
2b
S
O
9
11
98
93
1d
3i
SH
*
O
2b
S
O
1e
10
12
79
97
3j
a,b-unsaturated carbonyl compounds (0.5 mmol), thiols (0.6 mmol) and 20 mol % of tetra-n-butyl ammonium fluoride as the base additive in 1 mL of
a
Reaction conditions:
water.
b
Isolated yield of compounds.
Enantiomeric excess was determined by chiral HPLC.
c
20 mol % of tetra-n-butyl ammonium fluoride as additives at room
temperature without using any organic solvents. Further research
to prolong the opportunity of this new catalytic system is currently
in progress in our research laboratory.
4.3. General procedure for synthesis of (1S,2S,4S,5R)-2-((R)-
(allyloxy)(quinolin-4-yl)methyl)-1-benzyl-5-vinylquinuclidin-
1-ium bromide (N-(1-benzyl) cinchonidinium bromide) III
A mixture of compound II (1.5 g, 3.89 mmol) with allyl bromide
(0.71 g, 5.84 mmol) was stirred in 20 mL of dichloromethane at
room temperature for 15 min. This was followed by the dropwise
addition of 50% potassium hydroxide aqueous solution (10 mL)
into the reaction mixture at 0 °C. After completion of the addition,
the reaction mixture was stirred at room temperature for 3 h. Pro-
gress of the reaction was monitored by TLC. After completion of the
reaction, the reaction mixture was extracted with dichloromethane
(4 Â 25 mL) and the organic phase was dried over MgSO4 and con-
centrated under vacuum, and the crude product was triturated by
ether to afford III (0.76 g, 76% yield) as a yellow crystalline solid. 1H
NMR (400 MHz, DMSO) d: 1.24–1.31 (t, 1H), 1.82 (t, 1H), 1.99–2.01
(m, 3H), 2.02 (s, 1H) 3.30–3.50(m, 2H), 3.97–4.04 (m, 4H), 4.32–
4.34 (m, 1H), 4.91–4.99 (m, 2H), 5.10–5.16 (m, 2H), 5.29–5.32
(m, 1H), 5.44–5.49 (d, 1H), 5.70 (m, 1H), 6.13–6.17 (m, 1H), 6.43
(s, 1H), 7.59–7.60 (d, 3H), 7.69–7.71 (m, 3H), 7.72–7.73 (m, 1H),
7.74–7.90 (m, 1H), 8.13–8.14 (d, 1H), 8.15–8.16 (d, 1H), 9.01 (d
1H).
4. Experimental
4.1. General
All reagents and chemicals used were of analytical grade. Com-
mercial grade solvents were distilled prior to use. Benzyl bromide,
allylbromide, (+)-cinchonidine were obtained from Sigma Aldrich.
The completion of the reactions was checked by thin-layer chro-
matography (TLC) on aluminium plates coated with silica gel 60
F
254, 0.25 mm thickness (Merck) and detection of the components
was made by exposure to iodine vapours or UV light. 1H NMR spec-
tra were recorded in CDCl3 or DMSO-d6 on a Bruker Avance 400F
(MHz) spectrometer (Bruker Scientific Corporation Ltd, Switzer-
land) using the residual solvent signal as an internal standard at
400 MHz. Chemical shifts (d) are given in ppm and coupling con-
stants (J) are in Hz. Chiral HPLC analysis was carried out on CHIR-
ALPAK IC Analytical, 5
lm, 250 mm  4.6 mm Columns. HPLC
analysis was carried out on Agilent Series 1290 infinity High-Per-
formance Liquid Chromatograph. LCMS analysis was carried on
water ACQUITY UPLC H-class instrument.
4.4. General procedure for synthesis of compounds 3a–j
Thiol 2a–b (66 mg, 0.6 mmol) was added to a mixture of
a,b-
4.2. General procedure for synthesis of (1S,2S,4S,5R)-1-benzyl-2-
((R)-hydroxy(quinolin-4-yl)methyl)-5-vinylquinuclidin-1-ium
bromide II
unsaturated carbonyl compound 1a–e (48 mg, 0.5 mmol) and the
catalyst (allyloxy-N-(1-benzyl) cinchonidinium bromide) III
(10 mol %) in water (1.0 mL) at room temperature. The reaction
mixture was stirred, and the progress of the reaction was moni-
tored by TLC. After completion of the reaction, the reaction mixture
was extracted with ethyl acetate (4 Â 20 mL) and the organic
phase was dried using MgSO4 and concentrated under vacuum.
The crude product was purified over silica gel by column
chromatography.
A mixture of cinchonidine I (1.47 g, 5.0 mmol) with benzyl bro-
mide (0.94 g, 5.5 mmol) was stirred in 15 mL of toluene at 110 °C
for 1 h. After completion of the reaction, the reaction mixture
was cooled to room temperature. After cooling, the reaction mix-
ture was added drop wise to ether (100 mL) with stirring. The solid
precipitate was filtered and washed with ether (50 mL) and pen-
tane to afford II (1.73 g, 90% yield). 1H NMR (400 MHz, DMSO) d:
1.26–1.31 (t, 1H), 1.81 (t, 1H), 1.99–2.15 (m, 3H), 2.67 (br s, 1H)
3.23–3.35 (m, 2H), 3.69–3.72 (d, 1H), 3.88–3.92 (t, 1H), 4.23 (t,
1H), 4.94–4.97 (m, 2H), 5.08–5.16 (t, 2H), 5.63–5.72 (m, 1H), 6.56
(s, 1H), 6.74–6.75 (d, 1H), 7.57–7.59 (d, 3H), 7.69–7.87 (m, 5H),
8.10–8.12 (d, 1H), 8.26–8.28 (d, 1H), 8.98 (s, 1H).
4.4.1. 3-((4-Chlorophenyl)thio)-3-phenylpropanoic acid 3a
White solid, yield: 85%; ee: 100%, chiral HPLC: tR (3a major) =
4.34 min; 1H NMR (400 MHz, DMSO) d: 3.20 (d, 2H, J = 8.0 Hz),
5.47 (s, 1H), 7.62–8.08 (m, 9H), 12.56 (s, 1H); LC/MS (ESI): M+1
(C15H13ClO2S), found 293.8, calculated 292.7.