Regiospecific and diastereoselective aldol reaction of chiral N-sulfinyl metalloenamines with α,β-unsaturated trifluoromethyl ketones: Asymmetric synthesis of tertiary trifluoromethyl allylic carbinols

Article abstract of DOI:10.1016/j.jfluchem.2011.09.002

Regiospecific and diastereoselective aldol type reaction of chiral N-sulfinyl metalloenamines with α,β-unsaturated trifluoromethyl ketones was reported, which affords the corresponding tertiary trifluoromethyl allylic carbinols in high yields with good di

Full text of DOI:10.1016/j.jfluchem.2011.09.002

Journal of Fluorine Chemistry 133 (2012) 102–107
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Regiospecific and diastereoselective aldol reaction of chiral N-sulfinyl
metalloenamines with
a,b-unsaturated trifluoromethyl ketones: Asymmetric
synthesis of tertiary trifluoromethyl allylic carbinols
Zhen-Jiang Liu a,b, Fan Zhang b, Jin-Tao Liu b,
*
a School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai 201418, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Regiospecific and diastereoselective aldol type reaction of chiral N-sulfinyl metalloenamines with
a,b-
Received 25 June 2011
unsaturated trifluoromethyl ketones was reported, which affords the corresponding tertiary
trifluoromethyl allylic carbinols in high yields with good diastereoselectivities (dr up to 90:10). The
reduction of the condensation product 3a with LiBHEt3 and Catecholborane provides CF3-substituted
syn- and anti-1,3-amino alcohols 5a and 5b in high yields with excellent diastereoselectivities
(dr > 99:1).
Received in revised form 25 August 2011
Accepted 1 September 2011
Available online 7 September 2011
Keywords:
ß 2011 Elsevier B.V. All rights reserved.
N-Sulfinyl metalloenamine
a,b-Unsaturated trifluoromethyl ketone
Tertiary trifluoromethyl allylic carbinol
Asymmetric synthesis
1. Introduction
particular, N-tert-butanesulfinyl ketimines can be deprotonated to
form N-sulfinyl metalloenamines and further react witha number of
Trifluoromethyl-containing compounds have currently
attracted widespread interest in the fields of agricultural,
medicinal and material sciences [1] because the introduction of
a trifluoromethyl group with strong electron-withdrawing ability
can lead to significant changes in the physical, chemical, and
biological properties of the molecules. Among such compounds,
electrophiles, including aldehydes [8a,b], trifluoromethyl ketones
[8c], imines [8d,e] and alkylating agents [8f]. Recently, Ellman and
Peltier reported the conjugate addition of N-tert-butanesulfinyl
metalloenamines to
were obtained [9]. More recently, we described a highly diaster-
eoselective Michael addition of N-sulfinyl metalloenamines to
trifluoromethyl- -unsaturated ester and further expanded the
a,b-unsaturated ketones and only 1,4-adducts
b-
enantiomerically pure
a-trifluoromethyl tertiary alcohols have
a,b
received considerable attention [2] since they can serve as liquid
crystals [3a] and drugs such as Efavirenz (anti-HIV) [3b,c] and so
on. On the other hand, trifluoromethyl allylic alcohols are
increasingly popular as chiral synthons in the design of new
drugs or materials. However, few methods are available for their
asymmetric synthesis [4], especially for the synthesis of trifluoro-
methyl allylic carbinols bearing a stereogenic quaternary carbon
center [5]. Recently, our group and Yuan’s group have indepen-
dently developed an organocatalytic approach for the assemble of
tertiary trifluoromethyl allylic carbinols [6]. Nevertheless, the
substrate scope was largely limited. Therefore, it’s highly desirable
to develop new methods for the efficient synthesis of chiral tertiary
trifluoromethyl allylic carbinols.
scope of N-sulfinyl metalloenamine chemistry [10]. As a continua-
tion of our interests on the reactions of trifluoromethyl substituted
ketones [6a,8c,11], we found that in contrast to the reaction of N-
sulfinyl metalloenamines with nonfluorinated
a,b-unsaturated
ketones [9], the reaction of N-sulfinyl metalloenamines with
a,b-
unsaturated trifluoromethyl ketones proceeded only in 1,2-addition
mode and no 1,4-adducts were observed. Herein, we wish to report
the regiospecific and diastereoselective nucleophilic addition of
chiral N-sulfinyl metalloenamines to various
a,b-unsaturated
trifluoromethyl ketones, which provides a practical method for
theasymmetricsynthesisoftertiarytrifluoromethylallyliccarbinols
in high yields with good diastereoselectivities.
N-tert-Butanesulfinyl imines are versatile synthetic intermedi-
ates and are increasingly being used in organic synthesis [7]. In
2. Results and discussion
We began our investigation by examining the reaction of (R)-N-
tert-butanesulfinyl ketimine 1a and
a,b-unsaturated trifluoro-
methyl ketone 2a (as shown in Table 1). Deprotonation of 1a with
2.0 equiv. of LDA at ꢀ78 8C in THF followed by addition of 2a
* Corresponding author. Tel.: +86 21 54925188; fax: +86 21 64166128.
E-mail address: jtliu@sioc.ac.cn (J.-T. Liu).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.09.002

Z.-J. Liu et al. / Journal of Fluorine Chemistry 133 (2012) 102–107
103
Table 1
The reaction of 1a and 2a under different conditions
.
Entry
Solvent
LDA (equiv.)
Additive (equiv.)
Yield (%)a
3a:3a0:4b
1
THF
THF
THF
THF
THF
THF
THF
Et2O
2.0
1.5
1.5
1.5
1.5
1.5
1.5
1.5
–
32 (49:51)
63 (78:22)
71 (70:30)
98 (70:30)
25 (70:30)
>99 (87:13)
>99 (71:29)
61 (82:18)
15:15:70
52:15:32
49:21:31
67:30:3
69:31:0
87:13:0
71:29:0
82:18:0
2
–
3c
4c
5c
6c
7c
8c
–
ZnBr2 (1.5)
MgBr2 (2.0)
CuBr (2.0)
CuCN (1.2)
CuBr (1.0)
a
Isolated overall yield of 3a and 3a0. The diastereomeric ratio of 3a and 3a0 in parentheses.
Determined by 19F NMR spectroscopy of the crude reaction mixture.
b
c
The substrate 2a in the third step was cooled to ꢀ78 8C and then added.
afforded three new products, as indicated by 19F NMR spectroscopy
(quantitative yields and 87:13 dr) (Table 1, entry 6). Both changing
the solvent to Et2O and lowering the amount of CuBr led to a
decrease in the yield (Table 1, entry 8). It is noteworthy that no 1,4-
adduct was observed under all the tested reaction conditions.
Using the condition of entry 6 in Table 1, we next explored the
substrate scope of the condensation reaction with a variety of N-
monitoring of the crude reaction mixture (ꢀ80.01 ppm (d),
ꢀ81.35 ppm (s), ꢀ82.56 ppm (s)), which were identified as the
1,2-addition products 3a (ꢀ82.56 ppm) and 3a0 (ꢀ81.35 ppm) as
well as the reduction product 4 (ꢀ80.01 ppm) [12] from 1H, 13C,
and 19F NMR. Although the reaction gave 1,2-adducts in low yield
with poor selectivity (Table 1, entry 1), this is largely different from
the reaction of N-sulfinyl metalloenamines with nonfluorinated
(tert-butanesulfinyl) ketimines and
a,b-unsaturated trifluoro-
methyl ketones. As summarized in Table 2, all reactions took
place readily in 1,2-addition mode and afforded the corresponding
tertiary trifluoromethyl allylic carbinols in high yields with good
diastereoselectivities. N-Sulfinyl ketimines containing both aryl
and alkyl substituents proved to be excellent substrates for the
reaction (entries 1–7). It is worthwhile to mention that in the case
of N-sulfinyl ketimine 1 g the reaction occurred at the less
a,b-unsaturated ketones reported by Ellman and co-workers,
where only 1,4-addition occurred [9]. To achieve better results and
test the possibility of 1,4-addition [13], then the reaction
conditions were optimized by changing solvents or adding
additives. Lowering the amounts of LDA to 1.5 equiv. greatly
improved both the yields and the diastereoselectivities of 1,2-
adducts, and led to a dramatic decrease of the reduction product 4
(Table 1, entries 2–3). Furthermore, addition of metal salts could
thoroughly prevent the reduction reaction (Table 1, entries 4–8)
[14]. Among the metal salts tested, CuBr gave the best result
substituted
a-carbon selectively (entry 7). The reaction also
tolerated heteroaromatic substituted N-sulfinyl ketimine, giving
the condensation product in almost quantitative yield with a dr of
80:20 (entry 8). Additionally,
a,b-unsaturated trifluoromethyl
Table 2
The reaction of N-(tert-butanesulfinyl) ketimines 1 with
a,b-unsaturated trifluoromethyl ketones 2
.
Entry
R1
R2
Product
Yield (%)a
3:30 (dr)b
1
Ph (1a)
Ph (2a)
3a +3a0
3b + 3b0
3c + 3c0
3d + 3d0
3e + 3e0
3f + 3f0
3g + 3g0
3h +3h0
3i + 3i0
>99
97
87:13
83:17
80:20
85:15
86:14
73:27
90:10
80:20
83:17
88:12
88:12
2
4-MeOC6H4 (1b)
4-FC6H4 (1c)
4-ClC6H4 (1d)
4-NO2C6H4 (1e)
t-Bu (1f)
Ph (2a)
3
Ph (2a)
85
4
Ph (2a)
75
5
Ph (2a)
96
6
Ph (2a)
98
7
i-Pr (1g)
Ph (2a)
98
8
2-furyl (1h)
Ph (1a)
Ph (2a)
>99
89
9
4-MeOC6H4 (2b)
4-ClC6H4 (2c)
n-C8H17 (2d)
10
11
Ph (1a)
3j + 3j0
95
Ph (1a)
3k + 3k0
48
a
Isolated overall yield of 3 and 30.
Determined by 19F NMR spectroscopy of the crude reaction mixture.
b

104
Z.-J. Liu et al. / Journal of Fluorine Chemistry 133 (2012) 102–107
N-sulfinyl metalloenamines with a,b-unsaturated trifluoromethyl
ketones occurred in 1,2-addition mode regiospecifically to give the
corresponding allylic carbinols in high yields with good diaster-
eoselectivities. Further reduction of the condensation product 3a
with LiBHEt3 and Catecholborane provides CF3-substituted syn-
and anti-1,3-amino alcohols 5a and 5b in high yields with excellent
diastereoselectivities.
S
S
LiBHEt3
O
N
O
NH
HO
HO CF3
CF3
THF, -78 o
3h
C
Ph
Ph
Ph
Ph
Ph
(Rs, R)-3a
(Rs, 1S, 3R)-5a
96%, dr > 99:1
4. Experimental
S
S
Catecholborane
O
N
O
NH
HO
HO CF3
CF3
THF, -10 o
24h
C
4.1. General experimental methods
Ph
Ph
Ph
(Rs, R)-3a
(Rs, 1R, 3R)-5b
Unless otherwise mentioned, solvents and reagents were
purchased from commercial sources and used as received. N-
(tert-Butanesulfinyl) ketimines 1 were prepared using known
procedures [16]. THF and Et2O were freshly distilled over Na/
benzophenone. Melting points were measured on a Melt-Temp
apparatus and uncorrected. 1H NMR spectra were recorded on
Bruker AM-300 or Mercury 300 (300 MHz) spectrometers with
TMS as internal standard. 19F NMR spectra were recorded on
Bruker AM-300 or Mercury 300 (282 MHz) spectrometers with
CFCl3 as external standard. 13C NMR spectra were recorded on
Bruker 300 (75.5 MHz) or DPX-400 (100.7 MHz) spectrometers. IR
spectra were obtained with a Nicolet AV-360 spectrophotometer.
Mass spectra were taken on HP5989A or Shimadzu LCMS-2010EV
spectrometer. High-resolution mass data were obtained on a high-
resolution mass spectrometer in the EI or MALDI mode.
99%, dr > 99:1
Scheme 1. Stereoselective reduction of 3a with LiBHEt3 and Catecholborane.
4.2. General procedure for the 1,2-addition reaction of N-sulfinyl
metalloenamines 1 to
a,b-unsaturated trifluoromethyl ketones 2
Into a dried 20 mL Schlenk flask containing N-(tert-butanesul-
finyl) ketimine (R)-1 (0.3 mmol) in 2 mL THF was slowly added a
solution of LDA (0.23 mL, 0.46 mmol, 2 M solution in THF/heptane/
ethylenebenzene) at ꢀ78 8C under N2 atmosphere. After stirring at
ꢀ78 8C for 1 h, CuBr (0.6 mmol) was added and the solution was
stirred for 1 h. A solution of 2 (0.33 mmol) in 2 mL THF cooled to
ꢀ78 8C was added dropwise via cannula to the mixture and stirring
was continued at ꢀ78 8C for 5 h (monitored by TLC). After the
reaction was complete, the mixture was quenched with saturated
aqueous NH4Cl solution (5 mL) at ꢀ78 8C and then gradually
warmed to room temperature. The resulting mixture was
extracted with EtOAc (10 mL ꢁ 3). The combined organic solution
was dried over Na2SO4. After the removal of volatile solvents under
vacuum, the residue was further purified by silica gel column
chromatography to give product 3 and 30. The identity and purity of
the major diastereomer 3 was fully characterized.
Fig. 1. X-ray crystal structure of 5a.
ketones with different phenyl-substituents at the b-position could
also be applied to the reaction and high yields as well as good
diastereoselectivities were obtained (entries 9–10). However,
when
a
,b
-unsaturated trifluoromethyl ketone with an alkyl-
-position was used as the electrophile,
substituent at the
b
moderate yield was given albeit with good diastereoselectivity
(entry 11).
4.2.1. (Rs,R)-N-((E)-3-hydroxy-1,5-diphenyl-3-
(trifluoromethyl)pent-4-enylidene)-tert-butane sulfinamide (3a)
20
Further elaboration by stereoselective reduction of the conden-
sation product 3a with LiBHEt3 and Catecholborane, respectively,
gave CF3-substituted syn- and anti-1,3-amino alcohols 5a and 5b in
high yields with excellent diastereoselectivities (dr > 99:1)
(Scheme 1), which are of potential interest as building blocks
for biologically active compounds. The absolute configuration of 5a
was assigned to be (Rs, 1S, 3R) by X-ray crystallographic analysis
(Fig. 1) [15]. Therefore, we deduced the absolute configuration of
3a-k was (Rs, R) and the absolute configuration of 5b was (Rs, 1R,
3R) [8a,b].
White solid, yield 82%; [
(KBr, cmꢀ1):
1261, 1181, 1133, 1043, 1029; 1H NMR (CDCl3):
a
]
+569.67 (c = 0.88, CHCl3); FT-IR
D
n
3133, 2989, 2966, 1603, 1592, 1573, 1447, 1278,
7.60 (d, J = 6.9 Hz,
d
2H), 7.32–7.34 (m, 3H), 7.11–7.14 (m, 4H), 6.76–6.78 (m, 2H), 6.67
(d, J = 15.6 Hz, 1H), 5.71 (d, J = 15.6 Hz, 1H), 3.79 (AB, JAB = 12.8 Hz,
2H), 1.42 (s, 9H); 19F NMR (CDCl3):
d
ꢀ82.07 (s, 3F); 13C NMR
(CDCl3):
d 173.19, 140.54, 135.93, 132.98, 131.24, 128.74, 128.04,
127.72, 127.41, 126.47, 125.24 (q, J = 287.9 Hz), 124.99, 73.08 (q,
J = 29.0 Hz), 60.03, 37.50, 23.19; EI MS (m/z, %): 367 (M+-tBu + 1,
9.88), 319 (6.45), 57 (100.00); Anal. Calcd. for C22H24F3NO2S: C,
62.39; H, 5.71; N, 3.31. Found: C, 62.46; H, 5.53; N, 3.14.
3. Conclusions
4.2.2. (Rs,S)-N-((E)-3-hydroxy-1,5-diphenyl-3-
In summary, we have developed a practical method for the
asymmetric synthesis of tertiary trifluoromethyl allylic carbinols.
In the presence of CuBr, the condensation reaction of chiral
(trifluoromethyl)pent-4-enylidene)-tert-butane sulfinamide (3a0)
White solid; FT-IR (KBr, cmꢀ1):
n
3077, 2992, 2926, 2869, 1604,
1592, 1574, 1448, 1367, 1296, 1269, 1218, 1176, 1147, 1051, 1025;

Z.-J. Liu et al. / Journal of Fluorine Chemistry 133 (2012) 102–107
105
1H NMR (CDCl3):
d
7.64–7.70 (m, 2H), 7.39–7.41 (m, 3H), 7.14–7.24
4.2.7. (Rs,R)-N-((E)-3-hydroxy-1-(4-nitrophenyl)-5-phenyl-3-
(m, 3H), 6.99–7.10 (m, 2H), 6.94 (d, J = 15.6 Hz, 1H), 6.62 (s, 1H),
5.92 (d, J = 15.6 Hz, 1H), 3.83 (AB, JAB = 13.2 Hz, 2H), 1.38 (s, 9H);
(trifluoromethyl)pent-4-enylidene)-tert-butanesulfinamide (3e)
20
White solid, yield 45%; [
(KBr, cmꢀ1):
1260, 1188, 1166, 1137, 1043; 1H NMR (CDCl3):
a
]
+545.30 (c = 0.57, CHCl3); FT-IR
D
19F NMR (CDCl3):
d
ꢀ80.58 (s, 3F); 13C NMR (CDCl3):
d
171.46,
n
3213, 2956, 2863, 1601, 1587, 1520, 1450, 1345,
8.08 (d, J = 9.0 Hz,
139.82, 135.86, 133.02, 131.28, 128.60, 128.29, 127.95, 127.41,
126.74, 124.87 (q, J = 286.6 Hz), 124.75, 75.22 (q, J = 29.1 Hz),
59.96, 35.32, 23.36; EI MS (m/z, %): 367 (M+-tBu + 1, 11.00), 319
(7.95), 57 (100.00); HRMS (EI) calcd. for C18H16F3NO2S
[M+-tBu + 1]: 367.0854; Found: 367.0847.
d
2H), 7.68 (d, J = 9.0 Hz, 2H), 7.10–7.13 (m, 3H), 6.86 (s, 1H), 6.80-
6.83 (m, 2H), 6.59 (d, J = 15.6 Hz, 1H), 5.66 (d, J = 15.6 Hz, 1H), 3.81
(AB, JAB = 12.9 Hz, 2H), 1.45 (s, 9H); 19F NMR (CDCl3):
d
ꢀ81.60 (s,
3F); 13C NMR (CDCl3):
d 171.90, 148.72, 145.97, 135.05, 133.45,
129.42, 128.68, 128.31, 126.16, 125.43 (q, J = 294.5 Hz), 124.32,
123.79, 73.09 (q, J = 23.8 Hz), 60.60, 38.16, 23.21; ESI MS (m/z):
469.2 (M++1); HRMS (MALDI) calcd. for C22H24F3N2O4S+1 [M++1]:
469.1403; Found: 469.1412.
4.2.3. (E)-1,1,1-trifluoro-4-phenylbut-3-en-2-ol (4)
White solid; FT-IR (KBr, cmꢀ1):
n
3307, 2926, 1656, 1498, 1452,
1370, 1268, 1192, 1172, 1129, 1050; 1H NMR (CDCl3):
7.33–7.43
(m, 5H), 6.85 (d, J = 15.6 Hz, 1H), 6.20 (dd, J1 = 15.6 Hz, J2 = 6.6 Hz,
1H), 4.61–4.65 (m, 1H), 2.58 (s, 1H); 19F NMR (CDCl3):
ꢀ79.46 (d,
J = 4.8 Hz, 3F); 13C NMR (CDCl3):
136.29, 135.39, 128.73, 126.89,
d
d
4.2.8. (Rs,R)-N-((E)-5-hydroxy-2,2-dimethyl-7-phenyl-5-
d
(trifluoromethyl)hept-6-en-3-ylidene)-tert-butanesulfinamide (3f)
124.30 (q, J = 282.0 Hz), 120.71, 71.61 (q, J = 32.4 Hz); EI MS (m/z,
%): 202 (M+, 27.21), 133 (100.00); HRMS (EI) calcd. for C10H9F3O
[M+]: 202.0605; Found: 202.0614.
White solid, yield 51%; [
(KBr, cmꢀ1):
3039, 2990, 2865, 1600, 1480, 1446, 1366, 1280,
1257, 1178, 1143, 1030; 1H NMR (CDCl3):
7.66 (s, 1H), 7.27–7.40
(m, 5H), 6.90 (d, J = 15.3 Hz, 1H), 6.26 (d, J = 15.3 Hz, 1H), 3.27 (AB,
a]
20 +446.20 (c = 0.615, CHCl3); FT-IR
D
n
d
4.2.4. (Rs,R)-N-((E)-3-hydroxy-1-(4-methoxyphenyl)-5-phenyl-3-
JAB = 12.5 Hz, 2H), 1.34 (s, 9H), 1.12 (s, 9H); 19F NMR (CDCl3):
d
(trifluoromethyl)pent-4-enylidene)-tert-butanesulfinamide (3b)
ꢀ81.49 (s, 3F); 13C NMR (CDCl3):
d 184.85, 135.77, 132.99, 128.70,
White solid, yield 81%; [
(KBr, cmꢀ1):
3149, 2997, 2951, 1604, 1588, 1563, 1437, 1363,
1264, 1165, 1134, 1043, 1029; 1H NMR (CDCl3):
7.59 (d, J = 8.7 Hz,
a
]
20 +573.35 (c = 0.505, CHCl3); FT-IR
128.18, 126.83, 125.96, 125.37 (q, J = 288.7 Hz), 72.88 (q,
J = 28.1 Hz), 59.48, 43.91, 37.65, 29.22, 23.26; ESI MS (m/z):
404.2 (M++1); Anal. Calcd. for C20H28F3NO2S: C, 59.53; H, 6.99; N,
3.47. Found: C, 59.51; H, 7.07; N, 3.35.
D
n
d
2H), 7.20 (s, 1H), 7.11–7.16 (m, 3H), 6.83–6.86 (m, 2H), 6.80 (d,
J = 8.7 Hz, 2H), 6.64 (d, J = 15.6 Hz, 1H), 5.76 (d, J = 15.6 Hz, 1H),
3.74 (AB, JAB = 12.6 Hz, 2H), 3.73 (s, 3H), 1.40 (s, 9H); 19F NMR
4.2.9. (Rs,R)-N-((E)-5-hydroxy-2-methyl-7-phenyl-5-
(CDCl3):
d
ꢀ81.55 (s, 3F); 13C NMR (CDCl3):
d
171.96, 162.30,
(trifluoromethyl)hept-6-en-3-ylidene)-tert-butanesulfinamide (3g)
136.07, 132.90, 132.73, 129.43, 128.02, 127.66, 126.50, 125.32 (q,
J = 288.0 Hz), 125.11, 114.01, 73.20 (q, J = 28.5 Hz), 59.74, 55.36,
37.27, 23.13; ESI MS (m/z): 454.2 (M++1); Anal. Calcd. for
White solid, yield 88%; [
(KBr, cmꢀ1):
3100, 2968, 2870, 1627, 1465, 1447, 1365, 1286,
1257, 1184, 1149, 1028; 1H NMR (CDCl3):
7.28–7.41 (m, 5H), 7.16
a]
20 +509.34 (c = 0.815, CHCl3); FT-IR
D
n
d
C
23H26F3NO3S: C, 60.91; H, 5.78; N, 3.09. Found: C, 60.96; H,
(s, 1H), 6.96 (d, J = 15.9 Hz, 1H), 6.25 (d, J = 15.9 Hz, 1H), 3.23 (AB,
JAB = 12.0 Hz, 2H), 2.52 (7, J = 6.9 Hz, 1H), 1.32 (s, 9H), 1.11 (d,
5.73; N, 2.96.
J = 6.9 Hz, 3H), 0.88 (d, J = 6.9 Hz, 3H); 19F NMR (CDCl3):
d
ꢀ81.73
4.2.5. (Rs,R)-N-((E)-1-(4-fluorophenyl)-3-hydroxy-5-phenyl-3-
(s, 3F); 13C NMR (CDCl3):
d 184.24, 135.88, 133.34, 128.67, 128.21,
(trifluoromethyl)pent-4-enylidene)-tert-butanesulfinamide (3c)
126.74, 125.18 (q, J = 288.0 Hz), 124.55, 72.85 (q, J = 28.9 Hz),
59.19, 42.53, 40.92, 22.85, 21.16, 18.63; ESI MS (m/z): 390.2
(M++1); HRMS (MALDI) calcd. for C19H27F3NO2S+1 [M++1]:
390.1709; Found: 390.1716.
White solid, yield 60%; [
(KBr, cmꢀ1):
3155, 2968, 2930, 1612, 1581, 1509, 1462, 1367,
1280, 1261, 1184, 1167, 1135, 1019; 1H NMR (CDCl3):
7.59–7.63
a]
20 +562.67 (c = 0.615, CHCl3); FT-IR
D
n
d
(m, 2H), 7.15–7.17 (m, 3H), 7.11 (s, 1H), 6.96–7.02 (m, 2H), 6.84
(dd, J1 = 6.8 Hz, J2 = 2.9 Hz, 2H), 6.65 (d, J = 15.6 Hz, 1H), 5.73 (d,
J = 15.6 Hz, 1H), 3.76 (AB, JAB = 12.9 Hz, 2H), 1.42 (s, 9H); 19F NMR
4.2.10. (Rs,R)-N-((E)-1-(furan-2-yl)-3-hydroxy-5-phenyl-3-
(trifluoromethyl)pent-4-enylidene)-tert-butanesulfinamide (3h)
(CDCl3):
(CDCl3):
d
d
ꢀ81.61 (s, 3F), ꢀ107.97–108.07 (m, 1F); 13C NMR
White solid, yield 79%; [
(KBr, cmꢀ1):
3135, 2966, 2928, 1579, 1559, 1475, 1391, 1365,
1262, 1184, 1162, 1139, 1028; 1H NMR (CDCl3):
7.50 (d, J = 1.8 Hz,
a]
20 +546.87 (c = 0.475, CHCl3); FT-IR
D
171.83, 164.56 (d, J = 253.8 Hz), 136.70 (d, J = 3.2 Hz),
n
135.72, 133.09, 129.69 (d, J = 9.0 Hz), 128.21, 127.96, 126.35,
125.19 (q, J = 287.4 Hz), 124.74, 115.76 (d, J = 21.9 Hz), 73.10 (q,
J = 28.8 Hz), 60.04, 37.56, 23.19; ESI MS (m/z): 442.2 (M++1); Anal.
Calcd. for C22H23F4NO2S: C, 59.85; H, 5.25; N, 3.17. Found: C, 60.08;
H, 5.29; N, 2.97.
d
1H), 7.18–7.26 (m, 4H), 7.09–7.12 (m, 2H), 6.91 (d, J = 3.3 Hz, 1H),
6.75 (d, J = 15.3 Hz, 1H), 6.37 (dd, J1 = 3.3 Hz, J2 = 1.8 Hz, 1H), 6.16
(d, J = 15.3 Hz, 1H), 3.66 (AB, JAB = 12.8 Hz, 2H), 1.37 (s, 9H); 19F
NMR (CDCl3):
d
ꢀ81.63 (s, 3F); 13C NMR (CDCl3):
d 160.88, 153.43,
145.43, 136.10, 132.66, 128.27, 127.78, 126.63, 125.27 (q,
J = 287.5 Hz), 124.47, 114.69, 112.89, 73.17 (q, J = 29.4 Hz),
60.32, 36.81, 23.15; ESI MS (m/z): 414.2 (M++1); HRMS (MALDI)
calcd. for C20H22F3NO3SNa+1 [M++Na]: 436.1165; Found: 436.1177.
4.2.6. (Rs,R)-N-((E)-1-(4-chlorophenyl)-3-hydroxy-5-phenyl-3-
(trifluoromethyl)pent-4-enylidene)-tert-butanesulfinamide (3d)
White solid, yield 55%; [
(KBr, cmꢀ1):
3139, 2956, 2865, 1595, 1585, 1561, 1435, 1366,
1263, 1167, 1133, 1041, 1012; 1H NMR (CDCl3):
7.51 (d, J = 8.1 Hz,
a]
20 +525.24 (c = 0.765, CHCl3); FT-IR
D
n
d
4.2.11. (Rs,R)-N-((E)-3-hydroxy-5-(4-methoxyphenyl)-1-phenyl-3-
2H), 7.27 (d, J = 8.1 Hz, 2H), 7.16–7.18 (m, 3H), 7.06 (s, 1H), 6.79–
6.82 (m, 2H), 6.64 (d, J = 15.3 Hz, 1H), 5.69 (d, J = 15.3 Hz, 1H), 3.75
(trifluoromethyl)pent-4-enylidene)-tert-butanesulfinamide (3i)
20
White solid, yield 70%; [
(KBr, cmꢀ1):
1262, 1187, 1166, 1131, 1028; 1H NMR (CDCl3):
d
a
]
D
+624.69 (c = 0.82, CHCl3); FT-IR
(AB, JAB = 12.6 Hz, 2H), 1.42 (s, 9H); 19F NMR (CDCl3):
d
ꢀ81.61 (s,
n
3150, 2983, 2865, 1593, 1573, 1459, 1446, 1359,
7.57–7.60 (m,
3F); 13C NMR (CDCl3):
d
172.11, 139.00, 137.72, 135.70, 133.13,
128.96, 128.74, 128.24, 128.01, 126.37, 125.16 (q, J = 287.8 Hz),
124.80, 73.10 (q, J = 28.9 Hz), 60.16, 37.61, 23.21; ESI MS (m/z):
458.2 (M++1); HRMS (MALDI) calcd. for C22H23ClF3NO2SNa+1
[M++Na]: 480.0982; Found: 480.0997; Anal. Calcd. for
2H), 7.31–7.36 (m, 3H), 7.11 (s, 1H), 6.71 (d, J = 8.4 Hz, 2H), 6.64 (d,
J = 8.4 Hz, 2H), 6.59 (d, J = 15.6 Hz, 1H), 5.56 (d, J = 15.6 Hz, 1H),
3.78 (AB, JAB = 12.9 Hz, 2H), 3.75 (s, 3H), 1.42 (s, 9H); 19F NMR
(CDCl3):
d
ꢀ82.17 (s, 3F); 13C NMR (CDCl3):
d 173.34, 159.37,
C22H23ClF3NO2S: C, 57.70; H, 5.06; N, 3.06. Found: C, 58.09; H,
140.60, 132.29, 131.18, 128.76, 128.69, 127.70, 127.41, 125.30 (q,
5.22; N, 2.80.
J = 288.0 Hz), 122.79, 113.49, 73.08 (q, J = 28.3 Hz), 60.00, 55.17,

106
Z.-J. Liu et al. / Journal of Fluorine Chemistry 133 (2012) 102–107
37.63, 23.20; ESI MS (m/z): 454.2 (M++1); HRMS (MALDI) calcd. for
23H26F3NO3SNa+1 [M++Na]: 476.1478; Found: 476.1473.
removal of volatile solvents under vacuum, the residue was further
purified by column chromatography on silica gel to give product 5b
(45 mg) (16 mg of 3a was recovered).
C
4.2.12. (Rs,R)-N-((E)-5-(4-chlorophenyl)-3-hydroxy-1-phenyl-3-
(trifluoromethyl)pent-4-enylidene)-tert-butanesulfinamide (3j)
4.4.1. (Rs,1R,3R)-N-((E)-3-hydroxy-1,5-diphenyl-3-
White solid, yield 80%; [
(KBr, cmꢀ1):
3093, 2986, 2865, 1603, 1591, 1571, 1492, 1366,
1257, 1189, 1162, 1135, 1070, 1041; 1H NMR (CDCl3):
7.57–7.59
a
]
D
20 +590.54 (c = 1.065, CHCl3); FT-IR
(trifluoromethyl)pent-4-enyl)-tert-butane sulfinamide (5b)
n
White solid, yield 99%; FT-IR (KBr, cmꢀ1):
n
3227, 2981, 2928,
1425, 1369, 1285, 1263, 1178, 1136, 1076, 1027; 1H NMR (CDCl3):
7.44–7.47 (m, 2H), 7.29–7.39 (m, 8H), 7.13 (d, J = 15.6 Hz, 1H),
d
(m, 2H), 7.30–7.37 (m, 3H), 7.17 (s, 1H), 7.08 (d, J = 8.4 Hz, 2H), 6.68
(d, J = 8.4 Hz, 2H), 6.60 (d, J = 15.6 Hz, 1H), 5.68 (d, J = 15.6 Hz, 1H),
d
6.18 (d, J = 15.6 Hz, 1H), 5.79 (s, 1H), 4.62-4.70 (m, 1H), 4.40 (d,
J = 4.2 Hz, 1H), 3.04 (dd, J1 = 14.3 Hz, J2 = 12.0 Hz, 1H), 2.38 (d,
3.78 (AB, JAB = 12.9 Hz, 2H), 1.42 (s, 9H); 19F NMR (CDCl3):
d
ꢀ82.01
(s, 3F); 13C NMR (CDCl3):
d
173.12, 140.54, 134.41, 133.46, 131.73,
J = 14.3 Hz, 1H), 1.16 (s, 9H); 19F NMR (CDCl3):
d
ꢀ82.04 (s, 3F); EI
131.33, 128.78, 128.23, 127.68, 127.38, 125.73, 125.15 (q,
J = 287.1 Hz), 73.04 (q, J = 28.4 Hz), 60.02, 37.45, 23.16; ESI MS
(m/z): 458.2 (M++1); HRMS (MALDI) calcd. for C22H23ClF3NO2SNa+1
[M++Na]: 480.0982; Found: 480.1005.
MS (m/z, %): 320 (M+-tBu-SO, 6.32), 201 (100.00); HRMS (MALDI)
calcd. for C22H26F3NO2SNa+1 [M++Na]: 448.1529; Found: 448.1537.
Acknowledgements
4.2.13. (Rs,R)-N-((E)-3-hydroxy-1-phenyl-3-(trifluoromethyl)tridec-
Financial support from the National Natural Science Foundation
of China (No. 20872166) and Shanghai Institute of Technology (No.
YJ2011-56) is gratefully acknowledged.
4-enylidene)-tert-butanesulfinamide (3k)
20
Yellowish oil; [
cmꢀ1):
1047; 1H NMR (CDCl3):
a
]
+205.9 (c = 0.905, CHCl3); FT-IR (KBr,
D
n
3207, 2926, 2855, 1603, 1592, 1573, 1456, 1267, 1184,
7.51–7.60 (m, 2H), 7.28–7.41 (m, 3H),
d
References
6.81 (s, 1H), 5.67 (dt, J1 = 15.3 Hz, J2 = 6.9 Hz, 1H), 5.02 (d,
J = 15.3 Hz, 1H), 3.58 (AB, JAB = 12.9 Hz, 2H), 1.40–1.59 (m, 2H),
1.34 (s, 9H), 0.88–1.25 (m, 10H), 0.69–0.85 (m, 5H); 19F NMR
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d
ꢀ81.96 (s, 3F); 13C NMR (CDCl3):
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135.00, 131.44, 128.58, 127.65, 125.39 (q, J = 287.1 Hz), 124.57,
72.70 (q, J = 27.9 Hz), 60.01, 37.12, 31.88, 31.66, 29.36, 29.21,
29.10, 28.10, 23.29, 22.69, 14.11; ESI MS (m/z): 460 (M++1); HRMS
(MALDI) calcd. for C24H37F3NO2S [M++1]: 460.2492; Found:
460.2495.
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added LiBHEt3 (0.5 mL, 0.5 mmol, 1.0 M solution in THF) at ꢀ78 8C
and the resulting solution was stirred for 3 h. Then 5 mL of a
saturated aqueous solution of NH4Cl was added. The resulting
mixture was gradually warmed to room temperature and
extracted with EtOAc (10 mL ꢁ 3). The combined organic solution
was dried over Na2SO4. After the removal of volatile solvents under
vacuum, the residue was further purified by column chromatog-
raphy on silica gel to give product 5a (81 mg).
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(trifluoromethyl)pent-4-enyl)-tert-butane sulfinamide (5a)
White solid, yield 96%; mp 153–155 8C; FT-IR (KBr, cmꢀ1):
n
3285, 3163, 2960, 2929, 1494, 1456, 1367, 1285, 1255, 1180, 1147,
1028; 1H NMR (CDCl3):
7.26–7.37 (m, 10H), 7.08 (d, J = 15.6 Hz,
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3600–3740
d
1H), 6.16 (d, J = 15.6 Hz, 1H), 5.44 (s, 1H), 4.95–5.01 (m, 1H), 4.51
(d, J = 3.9 Hz, 1H), 2.53 (dd, J1 = 15.0 Hz, J2 = 3.9 Hz, 1H), 2.36 (dd,
J1 = 15.0 Hz, J2 = 9.0 Hz, 1H), 1.10 (s, 9H); 19F NMR (CDCl3):
d
ꢀ80.84 (s, 3F); EI MS (m/z, %): 369 (M+-tBu + 1, 10.59), 320 (12.61),
201 (100.00); Anal. Calcd. for C22H26F3NO2S: C, 62.10; H, 6.16; N,
3.29. Found: C, 62.36; H, 6.38; N, 2.98.
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To a solution of 3a (60 mg, 0.14 mmol) in 2 mL THF was slowly
added Catecholborane (0.75 mL, 0.75 mmol, 1.0 M solution in THF)
and the resulting solution was stirred for 24 h at ꢀ10 8C. To the
reaction mixture was added 1.5 mL of MeOH and 2.0 mL of a
saturated solution of sodium potassium tartrate. The resulting
mixture was stirred for 1 h, washed with 5 mL of brine, and the
aqueous layer was extracted with EtOAc (10 mL ꢁ 3). The
combined organic solution was dried over Na2SO4. After the

Z.-J. Liu et al. / Journal of Fluorine Chemistry 133 (2012) 102–107
107
(e) J. Xu, Z.-J. Liu, X.-J. Yang, L.-M. Wang, G.-L. Chen, J.-T. Liu, Tetrahedron 66
(2010) 8933–8937;
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(2006) 9998–9999, and references cited therein..
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[15] Crystallographic data (excluding structure factors) for the structure 5a in
this paper has been deposited to the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC 828123. Copies of the
data can be obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK. [fax: +44 0 1223 336033 or e mail: deposit@ccdc cam
ac uk].
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