6,6′-Bisperfluoroalkylated BINOLs promoted asymmetric allylation of aldehydes

Article abstract of DOI:10.1016/S0022-1139(02)00319-6

6,6′-Bis1H1H2H2H-perfluoroocty l)-1, 1′-bi-2-naphthol (Rf₆-BINOL) and 6,6′-bis(1H, 1H, 2H, 2H-perfluorodecyl)-1,1′-bi-2-naphthol (Rf₈-BINOL) were used in allylation of aldehydes in fluorous biphase system. Good enantioselectivity was

Full text of DOI:10.1016/S0022-1139(02)00319-6

Journal of Fluorine Chemistry 120 (2003) 117–120
6,60-Bisperfluoroalkylated BINOLs promoted asymmetric
allylation of aldehydes
Yue-yan Yin, Gang Zhao*, Zhan-shan Qian, Wei-xing Yin
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai, 200032, PR China
Received 1 August 2002; received in revised form 22 October 2002; accepted 29 October 2002
Abstract
6,60-Bis(1H, 1H, 2H, 2H-perfluorooctyl)-1, 10-bi-2-naphthol (Rf6-BINOL) and 6,60-bis(1H, 1H, 2H, 2H-perfluorodecyl)-1,10-bi-2-naphthol
(Rf8-BINOL) were used in allylation of aldehydes in fluorous biphase system. Good enantioselectivity was obtained and the ligands could be
recovered by continuos liquid–liquid extraction.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Rf-BINOL; Fluorous biphase; Asymmetric allylation
1. Introduction
allylation reaction of aldehydes in fluorous biphase systems
(FBS) according to Keck’s procedure [10a–d]. But the
BINOL–Ti(IV) complex (either 2:1 or 1:1) showed inferior
yields and enantioselectivities to those of Keck’s, irrespec-
tive to the presence of molecular sieve, at 0 or À20 8C. The
best result obtained in our hands was 67% yield and 89% e.e.
with 10% Ti complex (BINOL=TiðIVÞ ¼ 2 : 1). Inferior
yield and e.e. were also reported by other groups [11,12a–
d] (BINOL-derivative/Ti(IV) complex). The Rf-BINOL/
Ti(IV) catalyzed allylation of benzaldehy (as indicated in
Table 1) in dichloromathane (entry 3, Table 1) delivered even
worse result. One reason might be that this BINOL–Ti(IV)
system is too much sensitive to air and moisture, the other
might be that the solubility of the Rf-BINOL/Ti(IV) complex
in dichloromathane is not good. Although the Rf-BINOLs
could be totally dissolved in CH2Cl2, either BINOL or Rf-
BINOL could not be dissolved completely in hexane, not to
mention their Ti complexes (entries 1 and 2). The Rf-
BINOLs and their Ti(IV) complexes could be dissolved in
toluene, but the reaction was very sluggish (entry 4). Reac-
tion in benzotrifluoride as homogenous system delivered
good yield but no better enantiomeric selectivity (entry 5).
We found that the Rf-BINOL/Ti(IV) complex showed good
solubility in the fluorous biphase systems. With hexane,
dichloromethane and toluene as the organic phase and,
FC-72 (perfluorohexane, CF3(CF2)4CF3), perfluoromethyl-
cyclohexane and perfluorodecalin as the fluorous phase
respectively, the hexane-FC-72 solvent system was found
to be the best choice (entries 6–12) Scheme 1.
Homogeneous asymmetric catalysis is a powerful tool for
enantioselective transformations. Although a variety of
homogeneous chiral catalysts have been developed for
enantioselective reactions, recovery and purification of these
catalysts are always problematic. In the last few years,
fluorous chiral catalysts were discovered and applied in
fluorous biphase system to solve this problem. Several
fluorous catalysts were used for asymmetric carbon–carbon
bond formation [1–5], protonation [6], epoxidation [7] and
hydrogenation reaction [8]. Herein, we wish to report the
6,60-bisperfluoroalkylated BINOLs promoted asymmetric
allylation of aldehydes in fluorous biphase systems. Good
enantioselectivity was obtained and the ligands could be
recovered by liquid–liquid extraction. The recovered ligands
were reused without loss of activity.
2. Results and discussion
2.1. Asymmetric allylation of aldehydes catalyzed by
Rf-BINOL/Ti(IV) in fluorous biphase system
In continuation of our efforts in Rf-BINOL catalyzed
asymmetric reactions [9], we conducted the asymmetric
* Corresponding author. Fax: þ86-21-641-66128.
E-mail address: zhaog@pub.sioc.ac.cn (G. Zhao).
0022-1139/02/$ – see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 2 ) 0 0 3 1 9 - 6

118
Y.-y. Yin et al. / Journal of Fluorine Chemistry 120 (2003) 117–120
Table 1
3. Experimental
Asymmetric allylation of benzaldehyde catalyzed by Rf-BINOL/Ti(IV) in
homogenous and fluorous biphase system
3.1. General
Entry Ligand
(20 mol%)
Solvents
(ml)
Time Yield e.e.%
(R)a
(h)
(%)
All experiments were carried out under argon atmosphere
using Schlenk techniques. Commercial reagents were used
as received without further purification. Aldehydes were
distilled or recrystallized before use. Solvents were freshly
Homogenous
1
2
3
4
5
BINOL
Hexane
Hexane
CH2Cl2
Toluene
C6H5CF3
24
24
24
24
24
74
75
40
26
81
77.9
82.6
76.6
70.6
72.6
1
1
1
1
1
distilled by standard method. The H-NMR spectra were
1
obtained on a Bruker, AMX-300 spectrometer (TMS as H
internal reference). IR spectra were recorded with a Bio-Rad
FTS-185 spectrometer by films or KBr discs.
Biphase
6
7
1
2
1
1
1
2
1
CH2Cl2:C10F18
CH2Cl2:C10F18
Hexane:C10F18
24
24
12
27
20
76
78
85
83
52
81
26
75.6
74.9
83.2
87.7
90.1
89.8
48.2
81.3
49.1
3.2. Typical procedure for asymmetric allylation of
aldehydes
8
9
Hexane:C6F11CF3 10
10
11
12
13
14
Hexane:FC-72
Hexane:FC-72
Toluene:FC-72
10
5
Rf-BINOL 1 (196 mg, 0.2 mmol) was added into FC-72
(2 ml), which could not be totally dissolved, followed by
Ti(OPr-i)4 (30 ml, 0.1 mmol) in freshly distilled hexane (2 ml)
(entry 10 in Table 1 as an example). The mixture (dark
brown biphase system) was stirred at room temperature for
1 h then cooled to 0 8C and benzaldehyde (102 ml, 1 mmol)
was added and stirred for 10 min. Then allytributyltin
(0.34 ml, 1.1 mmol) was added and the reaction mixture
was kept at 0 8C until TLC inferred the disappearance of
benzaldehyde. The organic layer was moved out by syringe
and quenched by saturated NaHCO3 solution (1.5 ml). After
filtration, methanol (4 ml) and FC-72 (3 ml) were added for
three-phase extraction. Another two portions of FC-72 (3 ml)
were added for a second and a third extraction. The separated
organic layer was washed with saturated NaHCO3 and brine
and dried over anhydrous Na2SO4. After evaporation, the
residue was purified by flash chromatography. Optical rota-
12
24
24
1 (10 mol% 1:1)b Hexane:FC-72
1 (5 mol% 2:1) Hexane:FC-72
a The absolute configuration was determined by comparison with
reported specific rotation [10a]. The enaotioselectivities were determined
by chiral HPLC.
b The ratio referred to that of Ti to benzaldehyde.
We next examined this system for allylation of other
aldehydes. Disappointedly, only substrates with strong
electron withdrawing groups showed good yields and
enantioselectivities (entries 1–3, Table 2). The conver-
sions of p-chloro, p-bromo and 2,4-dicloro-benzaldehydes
were rather poor (entries 4, 5 and 7) and most of the
substrates were recovered. Aldehydes with electron donat-
ing groups showed no better results as could be predicted
(entries 8–10).
The mechanism of this reaction is still controversial.
Thus, the reasons for the unsatisfactory results are ambig-
uous. The BINOL/Ti(IV) complex is also believed to be
easily decomposed [11]. Bidentate complex and BINOL-
derivative/Ti(IV) complex showed better results [12c, e].
Optimization of this system is undergoing in our group
Scheme 2.
20
tion of the product was ½aꢀD þ 64.9 (c 3.3, CHCl3). Ligand 1
recovered from the organic phase was 24% (47 mg). The
combined fluorous solvent was distilled with little solvent left.
Ethyl acetate and saturated NaHCO3 were added. After
extraction, evaporation and column purification, 49%
(96 mg) of 1 was recovered.
20
(R)-1-Phenyl-3-buten-1-ol ½aꢀD þ 64.8 (c, 3.3, CHCl3);
IR (film, cmÀ1) 3388, 3076, 2925, 2854, 1641, 1492, 1453,
1260, 1196, 1049, 914, 872; 1H NMR (CDCl3) d 7.25–7.38
Scheme 1. Asymmetric allylation of benzaldehyde promoted by Rf-BINOL/Ti(IV).

Y.-y. Yin et al. / Journal of Fluorine Chemistry 120 (2003) 117–120
119
Table 2
Asymmetric allylation of aldehydes catalyzed by Rf-BINOL/Ti(IV) in fluorous biphase system
20
½aꢀD CHCl3
Entry
Substrate
Time (h)
Yield %
e.e.%a
1
2
4-Fluorobenzaldehyde
3-Fluorobenzaldehyde
3-Fluoro-5-trifluoromethyl-benzaldehyde
4-Chlorobenzaldehyde
4-Bromobenzaldehyde
2-Chlorobenzaldehyde
2,4-Dichlorobenzaldehyde
4-Methoxybenzaldehyde
4-Ethylbenzaldehyde
3
3
91
80.9
87.6
n.d.b
82.6
58.6
n.d.
54.0
47.0
31.4
33.9
24.0
53.8
43.9
32.1
33.9
24.5
À11.6c
38.7
86
81
3
3
4
10
12
12
12
12
24
24
24
12
51
5
12
6
83
16
7
n.d.
8
47
54.6
51.0
62.7
n.d.
9
25
21
10
11
12
4-Ethoxybenzaldehyde
Octanalaldehyde
Trace
31
3-Bromobenzaldehyde
76.0
The catalysts can be recovered by continuous extraction. Recovered ligands were used without obvious loss of activity.
a The absolute configurations were determined by comparison with reported specific rotation [10a]. The enantioselectivities were determined by chiral
HPLC.
b Not determined.
c In benzene.
(m, 5H, ArH), 6.73–6.89 (m, 1H, CH=CH2), 5.20–5.32 (m,
2H, CH=CH2), 4.70–4.78 (m, 1H, CHOH), 2.48–2.57 (m,
2H, CH2), 2.12 (s, 1H, OH).
CH=CH2), 5.11–5.19 (m, 2H, CH=CH2), 4.70 (t,
J ¼ 6:6 Hz, 1H, CHOH), 2.38–2.55 (m, 2H, CH2), 2.20
(s, 1H, OH).
20
20
(R)-1-(4-Fluorophenyl)-3-buten-1-ol ½aꢀD þ 54.0 (c, 1.1,
(R)-1-(4-Bromophenyl)-3-buten-1-ol ½aꢀD þ 24.0 (c, 3.5,
CHCl3); IR (film, cmÀ1) 3385, 2927, 1641, 1605, 1510,
1431, 1224, 1157, 1051, 836; 1H NMR (CDCl3) d 7.28–7.36
(m, 2H, ArH), 6.97–7.08 (m, 2H, ArH), 5.71–5.86 (m, 1H,
CH=CH2), 5.12–5.20 (m, 2H, CH=CH2), 4.72 (t,
J ¼ 6:6 Hz, 1H, CHOH), 2.40–2.56 (m, 2H, CH2), 2.09
(s, 1H, OH).
CHCl3); IR (film, cmÀ1) 3384, 3077, 2978, 2929, 1641,
1
1592, 1488, 1404, 1296, 1070, 1010, 918, 825; H NMR
(CDCl3) d 7.46 (dd, J1 ¼ 8:4 Hz, J2 ¼ 2:0 Hz, 2H, ArH),
7.22 (dd, J1 ¼ 8:7 Hz, J2 ¼ 2:1 Hz, 2H, ArH), 5.70–5.85
(m, 1H, CH=CH2), 5.12–5.20 (m, 2H, CH=CH2), 4.68 (t,
J ¼ 6:5 Hz), 2.38–2.52 (m, 2H, CH2), 2.22 (s, 1H, OH).
20
20
(R)-1-(3-Fluorophenyl)-3-buten-1-ol ½aꢀD þ 47.0 (c, 2.3,
(R)-1-(2-Chlorophenyl)-3-buten-1-ol ½aꢀD þ 53.8 (c, 1.1,
CHCl3); IR (film, cmÀ1) 3380, 3078, 2980, 2929, 1642, 1615,
CHCl3); IR (film, cmÀ1) 3396, 3074, 2979, 2923, 1641,
1
1
1591, 1488, 1248, 1139, 1052, 992, 920, 873; H NMR
1574, 1473, 1438, 1196, 1131, 1048, 987, 917, 872; H
(CDCl3) d 7.25–7.34 (m, 1H, ArH), 7.05–7.13 (m, 2H,
ArH), 6.91–6.99 (m, 1H, ArH), 5.70–5.85 (m, 1H, CH=CH2),
5.12–5.20 (m, 2H, CH=CH2), 4.70 (t, J ¼ 6:3 Hz, 1H,
CHOH), 2.38–2.57 (m, 2H, CH2), 2.25 (s, 1H, OH).
(R)-1-(3-Fluoro-5-trifluoromethylphenyl)-3-buten-1-ol
NMR (CDCl3) d 7.56 (dd, J1 ¼ 7:5 Hz, J2 ¼ 1:5 Hz, 1H,
ArH), 7.17–7.35 (m, 3H, ArH), 5.80–5.97 (m, 1H,
CH=CH2), 5.15–5.26 (m, 3H,), 2.58–2.69 (m, 1H), 2.32–
2.42 (m, 1H), 2.21 (s, 1H, OH).
20
(R)-1-(2, 4-Dichlorophenyl)-3-buten-1-ol ½aꢀD þ 43.9 (c,
20
½aꢀD þ 31.4 (c, 1.6, CHCl3); IR (film, cmÀ1) 3392, 3084,
3.2, CHCl3); IR (KBr, cmÀ1) 3382, 2999, 2939, 1639, 1590,
1470, 1220, 1070, 927, 823; 1H NMR (CDCl3) d 7.25–7.53
(m, 3H, ArH), 5.75–5.92 (m, 1H, CH=CH2), 5.07–5.22 (m,
3H,), 2.56–2.67 (m, 1H), 2.27–2.39 (m, 1H), 2.21 (s, 1H, OH).
2983, 2916, 1643, 1607, 1455, 1344, 1229, 1172, 1092,
1
1055, 924, 877; H NMR (CDCl3) d 7.25–7.53 (M, 3H,
ArH), 5.72–5.86 (m, 1H, CH=CH2), 5.15–5.24 (m, 2H,
CH=CH2), 4.80 (t, J ¼ 6:3 Hz), 2.38–2.51 (m, 2H, CH2),
2.20 (s, 1H, OH).
20
(R)-1-(4-Methyloxyphenyl)-3-buten-1-ol ½aꢀD þ 32.1 (c,
2.5, CHCl3); IR (film, cmÀ1) 3398, 2931, 2836, 1639, 1612,
1513, 1302, 1175, 1036, 916, 832; 1H NMR (CDCl3) d 7.24
(dd, J1 ¼ 8:7 Hz, J2 ¼ 2:0 Hz,.2H, ArH), 6.89 (dt,
J1 ¼ 8:4 Hz, J2 ¼ 2:4 Hz,.2H, ArH), 5.71–5.86 (m, 1H,
CH=CH2), 5.07–5.18 (m, 2H, CH=CH2), 4.68 (t, J ¼
20
(R)-1-(4-Chlorophenyl)-3-buten-1-ol ½aꢀD þ 33.9 (c, 1.1,
CHCl3); IR (film, cmÀ1) 3377, 3078, 2979, 2928, 1641,
1
1596, 1492, 1411, 1091, 1050, 919, 870, 829; H NMR
(CDCl3) d 7.25–7.34 (m, 4H, ArH), 5.70–5.84 (m, 1H,
Scheme 2. Asymmetric allylation of aldehyde promoted by Rf-BINOLs in FBS.

120
Y.-y. Yin et al. / Journal of Fluorine Chemistry 120 (2003) 117–120
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6:6 Hz, 1H, CHOH), 3.80 (s, 3H, OCH3), 2.48 (t, J ¼
7:1 Hz, 2H, CH2), 2.12 (s, 1H, OH).
[3] (a) Y. Tian, K.S. Chan, Tetrahedron Lett. 41 (2000) 8813–8816;
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20
(R)-1-(4-Ethylphenyl)-3-buten-1-ol ½aꢀD þ 33.9 (c, 1.1,
CHCl3); IR (film, cmÀ1) 3385, 3076, 3011, 2965, 2931,
1641, 1514, 1456, 1418, 1206, 1042, 1000, 914, 871; 832;
1H NMR (CDCl3) d 7.21 (dd, J1 ¼ 8:1 Hz, 4H, ArH), 5.74–
5.89 (m, 1H, CH=CH2), 5.10–5.20 (m, 2H, CH=CH2), 4.70
(t, J ¼ 7:5 Hz), 2.64 (q, J ¼ 7:7 Hz, 2H, CH2CH3), 2.46–
2.54 (m, 2H, CH2CH=CH2), 2.04 (s, 1H, OH), 1.42 (t,
J ¼ 7:5 Hz, 3H, CH3).
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20
(R)-1-(4-Ethyloxyphenyl)-3-buten-1-ol ½aꢀD þ 24.5 (c,
3.1, CHCl3); IR (film, cmÀ1) 3418, 2980, 2929, 1641,
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1
1612, 1512, 1393, 1244, 1174, 1116, 1048, 920, 834; H
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NMR (CDCl3) d 7.25 (dt, J1 ¼ 8:7 Hz, J2 ¼ 2:1 Hz, 2H,
ArH), 6.89 (dt, J1 ¼ 8:7 Hz, J2 ¼ 2:7 Hz, 2H, ArH), 5.85–
5.94 (m, 1H, CH=CH2), 5.09–5.18 (m, 2H, CH=CH2), 4.66
(t, J ¼ 6:7 Hz, 1H, CHOH), 4.00 (q, J ¼ 6:9 Hz, 2H,
OCH2), 2.44 (t, J ¼ 6:6 Hz, 2H, CH2), 2.12 (s, 1H, OH),
1.40 (t, J ¼ 7:1 Hz, 3H, CH3).
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Acknowledgements
We thank the National Nature & Science Foundation
(Grant No. D200032010), QT Program Foundation and
the Ministry of Sciences and Technology, the State Key
project of Basic Research (Project 973 No. G2000048007)
for funding this work.
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