Highly diastereoselective synthesis of α-trifluoromethylated α-propargylamines by acetylide addition to chiral CF3- substituted N-tert-butanesulfinyl ketimines

Article abstract of DOI:10.1016/j.tetasy.2010.11.028

A convenient and practical method for the preparation of enantiomerically pure α-trifluoromethylated α-propargylamines is described. A range of enantiopure α-trifluoromethylated α-propargyl sulfinamides were obtained by the addition of lithium acetylides

Full text of DOI:10.1016/j.tetasy.2010.11.028

Tetrahedron: Asymmetry 21 (2010) 2949–2955
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Highly diastereoselective synthesis of
a-trifluoromethylated a-propargylamines
by acetylide addition to chiral CF3-substituted N-tert-butanesulfinyl ketimines
Hengqiao Xiao a, Yangen Huang a, , Feng-Ling Qing a,b
⇑
a College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North Renmin Road, Shanghai 201620, 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:
A convenient and practical method for the preparation of enantiomerically pure
a
-trifluoromethylated
a-
Received 29 October 2010
Accepted 22 November 2010
Available online 11 January 2011
propargylamines is described. A range of enantiopure
a-trifluoromethylated a-propargyl sulfinamides
were obtained by the addition of lithium acetylides generated in situ with n-BuLi and terminal alkynes
to diverse chiral CF3-substituted (S)-N-tert-butanesulfinyl ketimines in moderate to excellent yields
(56–97%) and with uniformly excellent diastereoselectivities (>99:1) by using Ti(OiPr)4 as the catalyst
and THF as the polar solvent. Enantiomerically pure
a-trifluoromethylated a,a-dibranched propargyl
amines were then readily obtained in excellent yields (87–97%) by acidic cleavage of the tert-butanesul-
finyl group.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
CF3-substituted
drance of the ketimines. Recently, Zanda et al. have reported the
stereoselective synthesis of -trifluoromethylated -amino acid
a,a-dibranched amines due to the higher hin-
Fluorine-containing compounds have attracted considerable
attention due to the unique properties of fluorine (high electroneg-
ativity, low polarizability, relatively small size) which induce mod-
ifications of the physical properties for these compounds and make
them suitable for use in life and material sciences.1 Trifluoro-
methyl-containing compounds have attracted attention in recent
years in the pharmaceutical industry, which is reflected by the
many trifluoromethylated products on the market such as trifluri-
dine,2 efavirenz,3 fluoxetine (Prozac),4 and fluozolate.5 The trifluo-
romethyl group (CF3) is usually incorporated into organic
molecules by the transformation of trifluoromethyl-containing
building blocks or direct trifluoromethylation with nucleophilic
and electrophilic trifluoromethylating reagents.6 As an example,
the trifluoromethylation of carbonyl compounds with trimethyl-
(trifluoromethyl)silane, Me3SiCF3,7 has been well-elaborated from
which numerous CF3-substituted alcohols can be readily prepared.
In contrast, reactions of the C@N bond with Me3SiCF3 to obtain
CF3-substituted amines are limited due to the lower reactivity of
the C@N bond toward nucleophiles.8 Recently, the asymmetric
trifluoromethylations of imines or their equivalents with Me3SiCF3
by using chiral auxiliaries9 and the asymmetric additions of
nucleophiles to chiral trifluoromethylated aldimines10 have been
reported, which has facilitated the exploration of the potential use-
fulness of enantiomerically pure trifluoromethylated amines in
pharmaceutical and agrochemical science. However, most of these
methodologies are ineffective for the asymmetric construction of
a
a
derivatives via the reaction of an enantiomerically pure sulfinimine
of trifluoropyruvate with organometal reagents11 while Ellman
et al. reported the highly efficient asymmetric preparation of
a,a-dibranched propargyl amines via acetylide additions to N-
tert-butanesulfinyl ketimines.12 Inspired by these methodologies,
we herein report an alternative strategy for the diastereoselective
synthesis of CF3-substituted
a,a-dibranched amines by the addi-
tion of carbon nucleophiles to trifluoromethyl substituted keti-
mines using an N-tert-butanesulfinyl group as the chiral
auxiliary.13 Chiral CF3-substituted propargylamines, which are
important synthetic intermediates for the preparation of polyfunc-
tional amino derivatives,14 were obtained in good to excellent
yields and high diastereoselectivities.
2. Result and discussion
Chiral CF3-substituted (S)-N-tert-butanesulfinyl ketimines 1,
which are key precursors for the asymmetric synthesis of CF3-
substituted
a
-amino acids, were previously reported by Wang.15
In this context, four chiral CF3-substituted ketimines 1a–d
(Scheme 1) including aromatic and aliphatic substituents were
generated and isolated quickly prior to use, and were not fully
characterized due to their low hydrostability. Library substrate
screening of these ketimines to undergo 1,2-addition with lithium
acetylides was then conducted.
The representative preparation conditions for the 1,2-addition
of phenylethynyllithium (2.5 equiv) generated in situ with n-BuLi
and phenylacetylene to chiral CF3-substituted (S)-N-tert-butane-
⇑
Corresponding author. Tel.: +86 21 67792612; fax: +86 21 67792608.
E-mail address: hyg@dhu.edu.cn (Y. Huang).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.11.028

2950
H. Xiao et al. / Tetrahedron: Asymmetry 21 (2010) 2949–2955
O
S
O
S
O
N
Ti(O iPr)4
+
R1
NH2
F3C
hexane, r.t.
F3C
R1
1a R1 = Ph-; 1b R1 = p-MeOC6H4-;
(S)-tert-butanesulfinamide
1
1 = n-C6H13-;
1c
1d
R
R
= p-ClC6H4- ;
Scheme 1. Preparation of the CF3-substituted (S)-N-tert-butanesulfinyl ketimines 1.15
sulfinyl ketimine 1a are listed in Table 1. Firstly, the reaction was
conducted in toluene and gave the desired -trifluoromethylated
-propargyl sulfinamide 2a in low yield (34%) but in very high dia-
aryl ring which contains electron-withdrawing 1c or electron-
donating substituents 1b.
a
a
Researchers12,17 have previously reported low yields for the 1,2-
addition of lithium acetylides to the more sterically hindered N-
sulfinyl ketimines bearing a long aliphatic chain (<50%) or an aryl
group (<20%) either in toluene or in THF. However herein, we have
obtained a variety of sulfinamides 2a–2r with high yields and dia-
stereoselectivities, presumably due to the electron-withdrawing
nature of the CF3 group, which increases the reactivity of the sulfi-
nyl ketimines. Furthermore, the addition reactions were completed
within 10 min instead of 10–30 h for nonfluorine-containing sulfi-
nyl ketimines.12 Generally, the addition of lithium acetylides to
aldimines or ketimines provided a higher yield when the reaction
was carried out in nonpolar toluene than that in polar THF.12,17
However, a higher yield was achieved when polar THF was used
as the solvent in our reaction system. It is noteworthy that the tri-
methylsilyl groups in sulfinamides 2f and 2j were slowly deprotec-
ted during the work-up process and terminal acetylene
sulfinamides 2f’ and 2j0 could be obtained (Table 2, entries 6 and
10). The desilylation was completely accomplished for electron-
withdrawing group substituted aryl sulfinamide to afford the
terminal acetylene sulfinamide 2n (Table 2, entry 14), and no desi-
lylation was observed for alkyl sulfinamide 2r (Table 2, entry 18).
The absolute configuration of the addition product sulfinamide
2f was determined by X-ray crystallographic analysis which indi-
cated that the newly formed stereocenter had an (R)-configuration
(Fig. 1);18 the stereocenters of the other products were tentatively
assigned as (R) by analogy. A possible mechanism was proposed
based on the high diastereoselectivity observed and with previous
precidents.12,17,19 The addition of lithium acetylides to N-tert-
butanesulfinyl ketimines appears to proceed via a six-membered
chair-like transition state T (Scheme 2) in which the CF3 group pre-
fers to occupy the equatorial position rather than the axial position
due to the electrostatic repulsion between the CF3 and the lone
pairs of the sulfur atoms.
stereoselectivity (>99:1) based on the 19F NMR spectra of the crude
reaction mixture, from which no signal for the minor diastereomer
was detected and only one singlet at ꢀ76.56 ppm was presented
(Table 1, entry 1). Since a Lewis acid can coordinate with the chiral
sulfinylimines and improve both the yield and diastereoselectivity
of the 1,2-addition reaction,16 BF3ꢁEt2O was then tested using tolu-
ene as solvent, a slight improvement in the yield of 2a (43%) was
obtained again with excellent diastereoselectivity (Table 1, entry
2). When the reaction was carried out in THF and without a Lewis
acid, a significant improvement in the yield (66%) while keeping
excellent diastereoselectivity was obtained (Table 1, entry 3). The
yield of the addition reaction with THF as solvent can be further
improved to 77% and 90% by the addition of BF3ꢁEt2O and Ti(OiPr)4,
respectively (Table 1, entries 4 and 5). The influence of the amount
of phenylethynyllithium was also investigated; equivalents lower
than 2.5 resulted in lower yield but equivalents higher than 2.5 re-
sulted in no better yield (Table 1, entries 5 and 3).
Table 1
Effect of solvents and Lewis acids on the asymmetric 1,2-addition of lithium acetylide
to N-tert-butanesulfinyl ketimine 1aa
O
S
O
S
Solvent
Lewis acids
-78oC to r.t.
Ph
N
NH
+
Li
Ph
F3C
F3C
1a
Entry
2a
Solvent
Lewis acidb
Yieldc (%)
drd
1
2
3
4
5
Toluene
Toluene
THF
THF
THF
—
34
43
>99:1
>99:1
>99:1
>99:1
>99:1
BF3ꢁEt2O
—
69(66)e
77
Finally, the N-tert-butanesulfinyl group can be readily cleaved
under mild acidic condition (4 M HCl in dioxane) to provide
BF3ꢁEt2O
Ti(OiPr)4
90(79)f
the corresponding enantiomerically pure
a-trifluoromethylated
a
All reactions were conducted with 2.5 equiv lithium acetylide unless stated
otherwise.
a-propargylamine 3 in excellent yields with retention of configura-
b
tion, as summarized in Table 3. Free tertial amines 3 have not been
reported before; additionally, products 3 cannot be converted into
the corresponding hydrochloride salts, which may be due to a de-
crease in the basicity of the amino group in 3 by the high electron-
withdrawing effect of the CF3 group.
0.5 equiv of Lewis acid were added.
c
Isolated yield.
d
Diastereomeric ratios were determined by 19F NMR spectroscopy of the crude
reaction mixture.
e
In parentheses the yield is with 4.0 equiv of lithium acetylide.
In parentheses the yield is with 1.2 equiv of lithium acetylide.
f
3. Conclusion
Under the optimized condition [2.5 equiv of lithium acetylide
and 0.5 equiv of Ti(OiPr)4 in THF], the diastereoselective 1,2-addi-
tions of various lithium acetylides reagents to chiral CF3-substi-
tuted (S)-N-tert-butanesulfinyl ketimines 1 were screened. As
summarized in Table 2, lithium acetylides were successful in the
1,2-addition reaction to provide the corresponding sulfinamides
2 in moderate to excellent yields and exclusive diastereoselectivi-
ties based on the 19F NMR spectra of the crude reaction mixtures,
regardless of ketimines 1 bearing a long aliphatic chain 1d or an
In conclusion, we have provided a general and efficient method
for the formation of stereogenic quaternary centers, affording a
range of enantiomericaly pure a-trifluoromethylated a-propargyl-
amines with good yields and uniformly excellent diastereoselectiv-
ities (>99:1) via the 1,2-addition of lithium acetylides to
N-tert-butanesulfinyl ketimines in THF and successive acidic cleav-
age of the N-tert-butanesulfinyl groups. The Lewis acid Ti(OiPr)4
plays an important role in improving the yields of the addition

H. Xiao et al. / Tetrahedron: Asymmetry 21 (2010) 2949–2955
2951
Table 2
The 1,2-addition of lithium acetylides to N-tert-butanesulfinyl ketiminesa
O
S
N
O
S
R2
Ti(O iPr)4, THF
-78oC to r.t.
NH
Li
R2
+
R1
F3C
R1
F3C
2
1
Entry
N-Sulfinyl ketimines 1
R2
Productc
Yieldd (%)
dre
R1
Compound
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Ph
Ph
Ph
Ph
Ph
Ph
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1c
1c
1c
1c
1d
1d
1d
1d
Ph
2a
2b
2c
2d
2e
2fb
2g
2h
2i
2j
2k
2l
2m
2nf
2o
2p
2q
2r
90
88
82
83
57
74
77
72
75
73
80
77
67
56
89
97
94
72
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
Cyclopropyl
n-Hex
n-Bu
CF3
SiMe3
Ph
Cyclopropyl
n-Bu
SiMe3
Ph
Cyclopropyl
n-Bu
SiMe3
Ph
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
n-C6H11
n-C6H11
n-C6H11
n-C6H11
Cyclopropyl
n-Bu
SiMe3
a
b
c
d
e
f
All reactions were conducted with 2.5 equiv lithium acetylides unless stated otherwise.
Configurations were determined by X-ray crystallographic data.
Configurations were assigned from the transition-state model and deduced from 2f.
Isolated yields.
Diastereomeric ratios were determined by 19F NMR spectroscopy of the crude reaction mixture.
For 2n, R2 = H.
4. Experimental section
4.1. General
Unless otherwise noted, all reactions were carried out under
nitrogen and all reagents were obtained from commercial suppli-
ers and used without further purification. THF and hexane were
distilled from sodium/benzophenone ketyl and toluene was dis-
tilled from sodium immediately before use. N-tert-butanesulfinyl
ketimines were prepared according to Ref.14. Standard column
chromatography was performed on 300–400 mesh silica gel using
flash column chromatography techniques. IR spectra of liquids
were recorded as thin film on KBr plates and IR spectra of solids
were recorded as KBr pellets. Melting points were determined on
a Melt-Temp apparatus and are uncorrected. 1H NMR spectra were
recorded on Bruker AM-400 spectrometer with TMS as an internal
standard. 19F NMR spectra were recorded on Bruker AM-400 spec-
trometer with CFCl3 as an external standard. 13C NMR spectra were
recorded on a Bruker 400 (100.6 MHz) spectrometer. High Resolu-
tion MS spectra were taken on Bruker Daltonics, Inc.APEXIII 7.0 TE-
SLA FTMS.
4.2. Typical experimental procedure for the 1,2-addition of
lithium acetylides to N-tert-butanesulfinyl ketimines 1
Figure 1. X-ray crystal structure of (SS,R)-2f.
To a solution of phenylacetylene (255 mg, 2.5 mmol) in THF
was added dropwise n-BuLi (2.5 mmol) as a solution in hexane
(1.6 M) at ꢀ78 °C. The resulting solution was stirred for 1 h after
which a stirred THF solution (4 mL) of N-tert-butanesulfinyl keti-
mines 1 (1.0 mmol) and Ti(OiPr)4 (142 mg, 0.5 mmol) was slowly
added via cannula. The solution was then allowed to warm up to
room temperature. Usually, the reaction was completed after
reaction. It is noteworthy that the reactivity of sulfinyl ketimines
and the diastereoselectivty of the addition were improved by the
CF3 group. The method described may be applied to the asymmet-
ric synthesis of HIV protease inhibitor DPC 961 and its analogs.20

2952
H. Xiao et al. / Tetrahedron: Asymmetry 21 (2010) 2949–2955
R1
O
S
O
S
R2
S
Li
R2
F3C
N
NH
N
Li
O
Ti(O iPr)4
THF
M
F3C
R1
R2
F3C
R1
M = Ti(OiPr)4
1
2
T
Scheme 2. Proposed mechanism for the asymmetric addition reaction.
4.2.3. (SS,R)-(+)-N-(1,1,1-Trifluoro-2-phenyldec-3-yn-2-yl)-2-
Table 3
methylpropanesulfinamide 2c
Preparation of 3 from deprotection of 2
Colorless oil, yield 82%; ½a D24
¼ þ184:6 (c 1.0, CHCl3); IR (KBr,
ꢃ
O
S
cmꢀ1
) mmax 704, 1083, 1167, 1252, 1377, 1458, 2246, 2929, 3309;
R2
R2
H2N
F3C
1H NMR (400 MHz, CDCl3) d 0.91 (t, J = 7.0 Hz, 3H), 1.24 (s, 9H),
1.30–1.34 (m, 4H), 1.42–1.50 (m, 2H), 1.61–1.68 (m, 2H), 2.39 (t,
J = 7.2 Hz, 2H), 3.98 (s, 1H), 7.40–7.44 (m, 3H), 7.77 (t, J = 3.8 Hz,
2H); 13C NMR (100.6 MHz, CDCl3) d 14.00, 18.89, 22.54, 28.06,
28.53, 29.71, 31.25, 57.27, 63.38 (q, J = 28.2 Hz), 74.14, 92.63,
123.90 (q, J = 285.7 Hz), 128.26, 129.06, 129.62, 133.49; 19F NMR
(376 MHz, CDCl3) d ꢀ76.84 (s, 3F); MS (ESI): m/z = 388.1 [M+H]+;
HRMS (ESI) m/z calcd for C20H28F3NOS [M+Na]+: 410.1736, found:
410.1726.
NH
4M HCl in dioxane
CH3OH, r.t.
R1
F3C
R1
3
2
Entry R1
R2
Sulfinamide 2 Product 3 Yielda (%)
1
2
3
4
5
Ph
p-MeOC6H4 Cyclopropyl 2h
p-MeOC6H4 SiMe3 2j
Cyclopropyl 2p
SiMe3 2r
Cyclopropyl 2b
3a
3b
3c
3d
3e
90
97
93
87
97
n-C6H11
n-C6H11
4.2.4. (SS,R)-(+)-N-(1,1,1-Trifluoro-2-phenyloct-3-yn-2-yl)-2-
a
Isolated yields after chromatography.
methylpropanesulfinamide 2d
Colorless oil, yield 83%; ½a D25
¼ þ181:2 (c 1.0, CHCl3); IR (KBr,
ꢃ
cmꢀ1
) mmax 704, 805, 1088, 1166, 1254, 1375, 1460, 2246, 2957,
3209; 1H NMR (400 MHz, CDCl3) d 0.93 (t, J = 7.4 Hz, 3H), 1.22 (s,
9H), 1.43–1.52 (m, 2H), 1.58–1.67 (m, 2H), 2.38 (t, J = 7.2 Hz, 2H),
3.94 (s, 1H), 7.38–7.42 (m, 3H), 7.74 (t, J = 4.0 Hz, 2H); 13C NMR
(100.6 MHz, CDCl3) d 13.55, 18.59, 22.00, 22.58, 30.18, 57.25,
63.39 (q, J = 30.2 Hz), 92.54, 103.68, 123.89 (q, J = 285.7 Hz),
128.26, 129.07, 129.62, 133.47; 19F NMR (376 MHz, CDCl3) d
ꢀ76.90 (s, 3F); MS (ESI): m/z = 359.9 [M+H]+; HRMS (ESI) m/z calcd
for C18H24F3NOS [M+Na]+: 382.1423, found: 382.1416.
reaching room temperature, after which the reaction mixture
was cooled in an ice water bath and quenched with water
(2 mL). After 5 min, the mixture was filtered through Celite, after
which the filtrate was quenched by saturated aqueous NH4Cl
(15 mL) and diluted with EtOAc (15 mL). The organic layer was
removed and the aqueous layer was extracted with EtOAc
(15 mL ꢂ 2). The organic layers were combined and dried over
anhydrous Na2SO4, filtered, and concentrated. The residue was
purified by chromatography (silica gel, petroleum ether/ethyl
4.2.5. (SS,R)-(+)-N-(1,1,1,5,5,5-Hexafluoro-2-phenylpent-3-yn-2-
yl)-2-methylpropanesulfinamide 2e
acetate: 5/1) to give the enantiomerically pure
ated -propargyl sulfinamides 2.
a-trifluoromethyl-
a
A solution of 2-bromo-3,3,3-trifluoropropene (525 mg, 3.0
mmol) in THF (6 mL) was slowly added to a solution of LDA
(6.0 mmol, 3 mL, 2.0 M in THF/n-heptane/ethylbenzene) at
ꢀ78 °C. The resultant red/black solution was stirred at this temper-
ature for a further 1 h, and then applied to the procedure previ-
ously described. Pale yellow solid, yield 57%; mp 145–147 °C;
4.2.1. (SS,R)-(+)-N-(1,1,1-Trifluoro-2,4-diphenylbut-3-yn-2-yl)-2-
methylpropanesulfinamide 2a
Pale yellow solid, yield 90%; mp 71–72 °C; ½a D23
¼ þ339:2 (c 1.0,
ꢃ
CHCl3); IR (KBr, cmꢀ1
) mmax 696, 1008, 1073, 1172, 1240, 1455,
1487, 2240, 2969, 3212; 1H NMR (400 MHz, CDCl3) d 1.27 (s, 9H),
4.10 (s, 1H), 7.35–7.37 (m, 3H), 7.43–7.45 (m, 3H), 7.61 (dd,
J = 7.6, 1.6 Hz, 2H), 7.83 (t, J = 3.8 Hz, 2H); 13C NMR (100.6 MHz,
CDCl3) d 22.59, 57.45, 63.93 (q, J = 30.3 Hz), 82.89, 90.84, 121.35,
123.77 (q, J = 285.0 Hz), 128.37, 128.41, 129.18, 129.34, 129.86,
132.06, 132.99; 19F NMR (376 MHz, CDCl3) d ꢀ76.56 (s, 3F); MS
(ESI): m/z = 402.1 [M+Na]+; HRMS (ESI) m/z calcd for C20H20F3NOS
[M+Na]+: 402.1110, found: 402.1113.
½
a 2D5
ꢃ
¼ ꢀ202:2 (c 0.52, CHCl3); IR (KBr, cmꢀ1
) mmax 704, 1146,
1238, 1453, 1639, 2983, 3063; 1H NMR (400 MHz, CDCl3) d 1.41
(s, 9H), 7.40–7.45 (m, 3H), 7.67–7.69 (m, 2H), 8.17 (s, 1H); 13C
NMR (100.6 MHz, CDCl3) d 26.27, 66.45, 82.38 (q, J = 29.9 Hz),
122.33 (q, J = 272.4 Hz), 126.10 (q, J = 286.0 Hz), 130.43, 131.02,
131.75, 136.22, 136.87 (q, J = 37.9 Hz), 154.4; 19F NMR (376 MHz,
CDCl3) d ꢀ75.13 (s, 3F), ꢀ57.88 (s, 3F); MS (ESI): m/z = 394.0
[M+Na]+; HRMS (ESI) m/z calcd for C15H15F6NOS [M+Na]+:
394.0670, found: 394.0668.
4.2.2. (SS,R)-(+)-N-(4-Cyclopropyl-1,1,1-trifluoro-2-phenylbut-3-
4.2.6. (SS,R)-(+)-N-(1,1,1-Trifluoro-2-phenyl-4-
yn-2-yl)-2-methylpropanesulfinamide 2b
White solid, yield 88%; mp 47–49 °C; ½a D23
¼ þ365:1 (c 1.0,
ꢃ
(trimethylsilyl)but-3-yn-2-yl)-2-methylpropanesulfinamide 2f
White solid, yield 74%; mp 108–109 °C; ½a D24
¼ þ251:5 (c 1.0,
ꢃ
CHCl3); IR (KBr, cmꢀ1
) mmax 705, 1083, 1167, 1252, 1372, 1459,
CHCl3); IR (KBr, cmꢀ1
) mmax 850, 1073, 1160, 1196, 1253, 1372,
2244, 2963, 3180; 1H NMR (400 MHz, CDCl3) d 0.87–0.89 (m,
4H), 1.23 (s, 9H), 1.41–1.45 (m, 1H), 3.92 (s, 1H), 7.40–7.43 (m,
3H), 7.74 (t, J = 3.8 Hz, 2H); 13C NMR (100.6 MHz, CDCl3) d ꢀ0.32,
8.43 (2C), 22.59, 57.27, 63.38 (q, J = 30.2 Hz), 69.09, 95.36, 122.41
(q, J = 285.1 Hz), 128.24, 129.10, 129.62, 133.50; 19F NMR
(376 MHz, CDCl3) d ꢀ76.88 (s, 3F); MS (ESI): m/z = 344.4 [M+H]+;
HRMS (ESI) m/z calcd for C17H20F3NOS [M+Na]+: 366.1110, found:
366.1099.
1458, 2181, 2958, 3293; 1H NMR (400 MHz, CDCl3) d 0.27 (s, 9H),
1.23 (s, 9H), 3.94 (s, 1H), 7.39–7.44 (m, 3H), 7.75 (t, J = 3.8 Hz,
2H); 13C NMR (100.6 MHz, CDCl3) d 0.00, 23.06, 57.86, 64.12 (q,
J = 30.3 Hz), 97.73, 98.73, 124.12 (q, J = 285.8 Hz), 128.88, 129.39,
130.25, 133.44; 19F NMR (376 MHz, CDCl3) d ꢀ76.40 (s, 3F); MS
(ESI): m/z = 398.0 [M+Na]+; HRMS (ESI) m/z calcd for C17H24F3NOS-
Si [M+Na]+: 398.1192, found: 398.1190.

H. Xiao et al. / Tetrahedron: Asymmetry 21 (2010) 2949–2955
2953
4.2.7. (SS,S)-(+)-N-(1,1,1-Trifluoro-2-phenylbut-3-yn-2-yl)-2-
4.2.12. (SS,S)-(+)-N-(1,1,1-Trifluoro-2-(4-methoxyphenyl)but-3-
methylpropanesulfinamide 2f0
yn-2-yl)-2-methylpropanesulfinamide 2j0
Pale yellow oil, yield 5%; ½a D24
ꢃ
¼ þ154:6 (c 1.0, CHCl3); IR (KBr,
Pale yellow oil, yield 3%; ½a D25
¼ þ244:0 (c 1.0, CHCl3); IR
ꢃ
cmꢀ1
)
mmax 704, 840, 1012, 1074, 1172, 1251, 1460, 1658, 2119,
(KBr, cmꢀ1
) mmax 839, 1016, 1081, 1171, 1254, 1462, 1512,
2925, 3211, 3304; 1H NMR (400 MHz, CDCl3) d 1.26 (s, 9H), 3.00
(s, 1H), 4.10 (s, 1H), 7.41–7.46 (m, 3H), 7.77–7.79 (m, 2H); 13C
NMR (100.6 MHz, CDCl3) d 22.55, 57.50, 63.23 (q, J = 30.4 Hz),
77.74, 79.54, 124.52 (q, J = 285.3 Hz), 128.45, 129.20, 130.07,
131.68; 19F NMR (376 MHz, CDCl3) d ꢀ76.96 (s, 3F); MS (ESI): m/
z = 304.0 [M+H]+; HRMS (ESI) m/z calcd for C14H16F3NOS
[M+Na]+: 326.0797, found: 326.0804.
1612, 2116, 2962, 3208, 3300; 1H NMR (400 MHz, CDCl3) d
1.24 (s, 9H), 2.97 (s, 1H), 3.83 (s, 3H), 4.03 (s, 1H), 6.93 (dt,
J = 9.2, 3.2 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H); 13C NMR
(100.6 MHz, CDCl3) d 23.08, 55.86, 57.87, 63.31 (q, J = 30.5 Hz),
78.59, 79.74, 114.27, 123.81, 124.14 (q, J = 285.2 Hz), 131.22,
161.33; 19F NMR (376 MHz, CDCl3) d ꢀ77.32 (s, 3F); MS (ESI):
m/z = 334.0 [M+H]+; HRMS (ESI) m/z calcd for C15H18F3NO2S
[M+H]+: 334.1083, found: 334.1091.
4.2.8. (SS,R)-(+)-N-(1,1,1-Trifluoro-2-(4-methoxyphenyl)-4-
phenylbut-3-yn-2-yl)-2-methylpropanesulfinamide 2g
4.2.13. (SS,R)-(+)-N-(2-(4-Chlorophenyl)-1,1,1-trifluoro-4-
Pale yellow solid, yield 77%; mp 107–108 °C; ½a D24
ꢃ
¼ þ405:4 (c
phenylbut-3-yn-2-yl)-2-methylpropanesulfinamide 2k
1.0, CHCl3); IR (KBr, cmꢀ1
)
mmax 838, 1082, 1167, 1249, 1507,
Pale yellow oil, yield 80%; ½a D27
¼ þ184:9 (c 0.57, CHCl3); IR
ꢃ
1609, 2233, 2962, 3297; 1H NMR (400 MHz, CDCl3) d 1.27 (s, 9H),
3.84 (s, 3H), 4.06 (s, 1H), 6.95 (dt, J = 8.8, 3.2 Hz, 2H), 7.32–7.40
(m, 3H), 7.60–7.62 (m, 2H), 7.75 (d, J = 8.8 Hz, 2H); 13C NMR
(100.6 MHz, CDCl3) d 22.60, 55.33, 57.35, 63.47 (q, J = 30.5 Hz),
83.22, 90.51, 113.70, 121.39, 123.83 (q, J = 285.1 Hz), 124.61,
128.35, 129.28, 130.66, 132.04, 160.66; 19F NMR (376 MHz, CDCl3)
d ꢀ76.94 (s, 3F); MS (ESI): m/z = 432.0 [M+Na]+; HRMS (ESI) m/z
calcd for C21H22F3NO2S [M+Na]+: 432.1216, found: 432.1221.
(KBr, cmꢀ1
) mmax 690, 751, 1012, 1085, 1174, 1241, 1487, 1584,
1637, 2235, 2963, 3445; 1H NMR (400 MHz, CDCl3) d 1.26 (s, 9H),
4.06 (s, 1H), 7.34–7.43 (m, 5H), 7.61 (dd, J = 8.0, 1.6 Hz, 2H), 7.77
(d, J = 8.4 Hz, 2H); 13C NMR (100.6 MHz, CDCl3) d 22.58, 57.58,
63.54 (q, J = 30.5 Hz), 82.41, 91.18, 121.07, 123.56 (q,
J = 285.5 Hz), 128.43, 128.68, 129.52, 130.74, 131.48, 132.07,
136.22; 19F NMR (376 MHz, CDCl3) d ꢀ76.76 (s, 3F); MS (ESI): m/
z = 414.0 [M+H]+; HRMS (ESI) m/z calcd for C20H19F3ClNOS
[M+Na]+: 436.0720, found: 436.0727.
4.2.9. (SS,R)-(+)-N-(4-Cyclopropyl-1,1,1-trifluoro-2-(4-
methoxyphenyl)but-3-yn-2-yl)-2-methylpropanesulfinamide
2h
4.2.14. (SS,R)-(+)-N-(2-(4-Chlorophenyl)-4-cyclopropyl-1,1,1-
trifluorobut-3-yn-2-yl)-2-methylpropanesulfinamide 2l
White solid, yield 72%; mp 112–113 °C; ½a D23
ꢃ
¼¼ þ387:4 (c 1.0,
White solid, yield 77%; mp 136–137 °C; ½a D28
¼ þ264:9 (c 0.59,
ꢃ
CHCl3); IR (KBr, cmꢀ1
)
mmax 1024, 1082, 1166, 1253, 1461, 1511,
CHCl3); IR (KBr, cmꢀ1
) mmax 933, 1018, 1063, 1172, 1416, 1580,
1611, 2244, 2959, 3199; 1H NMR (400 MHz, CDCl3) d 0.85–0.87
(m, 4H), 1.22 (s, 9H), 1.38–1.43 (m, 1H), 3.83 (s, 3H), 3.88 (s, 1H),
6.91 (dt, J = 9.2, 3.2 Hz, 2H), 7.64 (d, J = 8.8 Hz, 2H); 13C NMR
(100.6 MHz, CDCl3) d 0.00, 8.74, 8.76, 22.92, 55.63, 57.48, 63.23
(q, J = 30.2 Hz), 69.72, 95.262, 113.84, 124.18 (q, J = 285.1 Hz),
125.44, 130.92, 160.80; 19F NMR (376 MHz, CDCl3) d ꢀ77.22 (s,
3F); MS (ESI): m/z = 374.0 [M+H]+; HRMS (ESI) m/z calcd for
1637, 2252, 2971, 3445; 1H NMR (400 MHz, CDCl3) d 0.88 (d,
J = 6.8 Hz, 4H), 1.22 (s, 9H), 1.37–1.45 (m, 1H), 3.88 (s, 1H), 7.37
(dt, J = 8.8, 2.8 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H); 13C NMR
(100.6 MHz, CDCl3) d ꢀ0.37, 8.47 (2C), 22.55, 57.37, 62.98 (q,
J = 30.3 Hz), 68.70, 95.73, 123.56 (q, J = 285.5 Hz), 128.47, 130.67,
131.96, 135.94; 19F NMR (376 MHz, CDCl3) d ꢀ77.05 (s, 3F); MS
(ESI): m/z = 378.0 [M+H]+; HRMS (ESI) m/z calcd for C17H19F3ClNOS
[M+Na]+: 400.0720, found: 400.0732.
C
18H22F3NO2S [M+Na]+: 396.1216, found: 396.1215.
4.2.10. (SS,R)-(+)-N-(1,1,1-Trifluoro-2-(4-methoxyphenyl)oct-3-
4.2.15. (SS,R)-(+)-N-(2-(4-Chlorophenyl)-1,1,1-trifluorooct-3-yn-
yn-2-yl)-2-methylpropanesulfinamide 2i
2-yl)-2-methylpropanesulfinamide 2m
White solid, yield 75%; mp 80–81 °C; ½a D24
ꢃ
¼ þ412:4 (c 1.0,
White solid, yield 67%; mp 69–71 °C; ½a D28
¼ þ221:0 (c 0.5,
ꢃ
CHCl3); IR (KBr, cmꢀ1
)
mmax 851, 1014, 1106, 1243, 1468, 1516,
CHCl3); IR (KBr, cmꢀ1
) mmax 932, 1061, 1170, 1415, 1458, 1569,
1609, 2252, 2964, 3321; 1H NMR (400 MHz, CDCl3) d 0.94 (t,
J = 7.4 Hz, 3H), 1.23 (s, 9H), 1.44–1.51 (m, 2H), 1.58–1.64 (m, 2H),
2.38 (t, J = 7.2 Hz, 2H), 3.83 (s, 3H), 3.92 (s, 1H), 6.92 (dt, J = 9.2,
3.2 Hz, 2H), 7.68 (d, J = 8.8 Hz, 2H); 13C NMR (100.6 MHz, CDCl3)
2251, 2928, 3437; 1H NMR (400 MHz, CDCl3) d 0.94 (t, J = 7.4 Hz,
3H), 1.23 (s, 9H), 1.41–1.51 (m, 2H), 1.58–1.66 (m, 2H), 3.94 (s,
1H), 2.39 (t, J = 7.2 Hz, 2H), 7.38 (dt, J = 8.8, 2.8 Hz, 2H), 7.70 (d,
J = 8.4 Hz, 2H); 13C NMR (100.6 MHz, CDCl3) d 13.54, 18.58, 22.00,
22.55, 30.10, 57.35, 62.98 (q, J = 30.3 Hz), 73.79, 92.91, 123.65 (q,
J = 285.4 Hz), 128.50, 130.66, 131.91, 135.94; 19F NMR (376 MHz,
CDCl3) d ꢀ77.09 (s, 3F); MS (ESI): m/z = 394.0 [M+H]+; HRMS
(ESI) m/z calcd for C18H23F3ClNOS [M+Na]+: 416.1033, found:
416.1044.
d
14.00, 19.05, 22.46, 23.04, 30.66, 55.75, 57.58, 63.41 (q,
J = 30.2 Hz), 74.97, 92.57, 114.02, 124.43 (q, J = 285.2 Hz), 125.59,
131.03, 160.98; 19F NMR (376 MHz, CDCl3) d ꢀ77.24 (s, 3F); MS
(ESI): m/z = 412.1 [M+Na]+; HRMS (ESI) m/z calcd for C19H26F3NO2S
[M+Na]+: 412.1529, found: 412.1537.
4.2.11. (SS,R)-(+)-N-(1,1,1-Trifluoro-2-(4-methoxyphenyl)-4-
4.2.16. (SS,S)-(+)-N-(2-(4-Chlorophenyl)-1,1,1-trifluorobut-3-yn-
(trimethylsilyl)but-3-yn-2-yl)-2-methylpropanesulfinamide 2j
2-yl)-2-methylpropanesulfinamide 2n
Colorless oil, yield 73%; ½a D26
ꢃ
¼ þ238:1 (c 1.0, CHCl3); IR (KBr,
Pale yellow oil, yield 56%; ½a D28
¼ þ47:0 (c 0.43, CHCl3); IR (KBr,
ꢃ
cmꢀ1
)
vmax 845, 1088, 1169, 1252, 1462, 1512, 1617, 2182, 2692,
cmꢀ1
) mmax 830, 1014, 1087, 1175, 1250, 1405, 1483, 1579, 2120,
3441; 1H NMR (400 MHz, CDCl3) d 0.27 (s, 9H), 1.22 (s, 9H), 3.83
(s, 3H), 3.94 (s, 1H), 6.93 (dt, J = 8.8, 3.2 Hz, 2H), 7.67 (d,
J = 8.8 Hz, 2H); 13C NMR (100.6 MHz, CDCl3) d 0.00, 23.06, 55.79,
57.75, 63.62 (q, J = 30.3 Hz), 97.22, 99.08, 114.15, 124.20 (q,
J = 285.4 Hz), 124.98, 130.88, 161.03; 19F NMR (376 MHz, CDCl3)
d ꢀ76.72 (s, 3F); MS (ESI): m/z = 406.1 [M+H]+; HRMS (ESI) m/z
calcd for C18H26F3NO2SSi [M+Na]+: 428.1298, found: 428.1306.
2924, 3302, 3433; 1H NMR (400 MHz, CDCl3) d 1.25 (s, 9H), 3.01
(s, 1H), 4.06 (s, 1H), 7.41 (dt, J = 8.8, 2.8 Hz, 2H), 7.72 (d,
J = 8.4 Hz, 2H); 13C NMR (100.6 MHz, CDCl3) d 22.51, 57.59, 61.10,
62.81 (q, J = 30.4 Hz), 79.88, 123.32 (q, J = 285.5 Hz), 128.72,
13017, 130.72, 136.44; 19F NMR (376 MHz, CDCl3) d ꢀ77.13 (s,
3F); MS (ESI): m/z = 338.0 [M+H]+; HRMS (ESI) m/z calcd for
C
14H15F3ClNOS [M+Na]+: 360.0407, found: 360.0420.

2954
H. Xiao et al. / Tetrahedron: Asymmetry 21 (2010) 2949–2955
4.2.17. (SS,R)-(+)-N-(1-Phenyl-3-(trifluoromethyl)non-1-yn-3-
was purified by chromatography (silica gel, petroleum ether/ethyl
acetate: 40/1, 20/1) to afford the enantiomerically active -trifluo-
romethylated -propargylamine 3.
yl)-2-methylpropanesulfinamide 2o
a
White solid, yield 89%; mp 91–92 °C; ½a D24
ꢃ
¼ þ86:8 (c 1.0,
a
CHCl3); IR (KBr, cmꢀ1
) mmax 689, 749, 1052, 1179, 1259, 1458,
2240, 2951, 3127; 1H NMR (400 MHz, CDCl3) d 0.90 (t, J = 7.0 Hz,
3H), 1.26 (s, 9H), 1.26–1.43 (m, 6H), 1.68–1.77 (m, 2H), 1.95–
2.07 (m, 2H), 3.58 (s, 1H), 7.31–7.40 (m, 3H), 7.47 (dd, J = 8.0,
2.0 Hz, 2H); 13C NMR (100.6 MHz, CDCl3) d 14.02, 22.49, 22.59,
23.82, 29.19, 31.57, 35.02, 57.21, 61.33 (q, J = 29.9 Hz), 82.20,
88.66, 121.29, 124.53 (q, J = 286.1 Hz), 128.41, 129.30, 131.97;
19F NMR (376 MHz, CDCl3) d ꢀ77.75 (s, 3F); MS (ESI): m/z = 410.3
[M+Na]+; HRMS (ESI) m/z calcd for C20H28F3NOS [M+Na]+:
410.1736, found: 410.1743.
4.3.1. (R)-(+)-4-Cyclopropyl-1,1,1-trifluoro-2-phenylbut-3-yn-2-
amine 3a
Pale yellow oil, yield 90%; ½a D29
¼ þ32:4 (c 1.0, CHCl3); IR (KBr,
ꢃ
cmꢀ1 mmax 708, 933, 1166, 1453, 1634, 2242, 2926, 3401; 1H
)
NMR (400 MHz, CDCl3) d 0.75–0.86 (m, 4H), 1.32–1.37 (m, 1H),
2.06 (s, 2H), 7.38–7.40 (m, 3H), 7.76–7.78 (m, 2H); 13C NMR
(100.6 MHz, CDCl3) d 1.77, 10.65, 10.69, 61.33 (q, J = 30.3 Hz),
75.61, 92.44, 126.93 (q, J = 284.3 Hz), 129.96, 130.51, 131.34,
138.84; 19F NMR (376 MHz, CDCl3) d ꢀ79.27 (s, 3F); MS (ESI): m/
z = 262.1 [M+Na]+; HRMS (ESI) m/z calcd for C13H12F3N [M+Na]+:
262.0814, found: 262.0810.
4.2.18. (SS,R)-(+)-N-(1-Cyclopropyl-3-(trifluoromethyl)non-1-
yn-3-yl)-2-methylpropanesulfinamide 2p
White solid, yield 97%; mp 104 °C; ½a D24
¼ þ102:2 (c 1.0,
ꢃ
4.3.2. (R)-(+)-4-Cyclopropyl-1,1,1-trifluoro-2-(4-
CHCl3); IR (KBr, cmꢀ1
) mmax 730, 909, 1047, 1172, 1267, 1461,
methoxyphenyl)but-3-yn-2-amine 3b
2250, 2951, 3108; 1H NMR (400 MHz, CDCl3) d 0.71–0.74 (m,
2H), 0.81–0.86 (m, 2H), 0.89 (t, J = 6.6 Hz, 3H), 1.22 (s, 9H),
1.26–1.34 (m, 7H), 1.51–1.67 (m, 2H), 1.87 (t, J = 8.4 Hz, 2H),
3.42 (s, 1H); 13C NMR (100.6 MHz, CDCl3) d 0.00, 9.00, 9.06,
14.65, 23.11, 23.21, 24.30, 29.80, 32.19, 35.55, 57.63, 61.42 (q,
J = 29.6 Hz), 69.12, 93.61, 125.16 (q, J = 286.0 Hz); 19F NMR
Pale yellow oil, yield 97%; ½a D29
¼ þ18:5 (c 1.0, CHCl3); IR (KBr,
ꢃ
cmꢀ1
) mmax 831, 934, 1032, 1164, 1252, 1458, 1511, 1610, 2241,
2929, 3011, 3394; 1H NMR (400 MHz, CDCl3) d 0.74–0.78 (m,
2H), 0.80–0.86 (m, 2H), 1.31–1.38 (m, 1H), 2.08 (s, 2H), 3.81 (s,
3H), 6.90 (dt, J = 8.8, 3.2 Hz, 2H), 7.68 (d, J = 8.8 Hz, 2H); 13C NMR
(100.6 MHz, CDCl3) d 0.00, 8.87, 8.91, 55.86, 59.11 (q, J = 30.3 Hz),
74.08, 90.48, 114.03, 125.24 (q, J = 284.1 Hz), 129.10, 129.49,
160.64; 19F NMR (376 MHz, CDCl3) d ꢀ79.53 (s, 3F); MS (ESI): m/
z = 292.1 [M+Na]+; HRMS (ESI) m/z calcd for C14H14F3NO
[M+Na]+: 292.0920, found: 292.0918.
(376 MHz, CDCl3)
d
ꢀ78.16 (s, 3F); MS (ESI): m/z = 374.2
[M+Na]+; HRMS (ESI) m/z calcd for C17H28F3NOS [M+H]+:
352.1917, found: 352.1914.
4.2.19. (SS,R)-(+)-N-(7-(Trifluoromethyl)tridec-5-yn-7-yl)-2-
methylpropanesulfinamide 2q
White solid, yield 94%; mp 78–79 °C; ½a D24
¼ þ101:9 (c 1.0,
ꢃ
4.3.3. (R)-(+)-1,1,1-Trifluoro-2-(4-methoxyphenyl)-4-
CHCl3); IR (KBr, cmꢀ1
) mmax 600, 720, 878, 1054, 1171, 1373,
(trimethylsilyl)but-3-yn-2-amine 3c
Pale yellow oil, yield 93%; ½a D27
¼ þ2:0 (c 0.49, CHCl3); IR (KBr,
ꢃ
1464, 2254, 2864, 3954, 3148; 1H NMR (400 MHz, CDCl3) d 0.88–
0.94 (m, 6H), 1.23 (s, 9H), 1.27–1.65 (m, 12H), 1.87–1.91 (m, 2H),
2.25 (t, J = 7.0 Hz, 2H), 3.44 (s, 1H); 13C NMR (100.6 MHz, CDCl3)
d 14.11, 14.65, 18.91, 22.45, 23.11, 23.19, 24.34, 29.79, 30.81,
32.20, 35.62, 57.63, 61.45 (q, J = 29.7 Hz), 74.16, 90.65, 125.21 (q,
J = 286.7 Hz); 19F NMR (376 MHz, CDCl3) d ꢀ78.22 (s, 3F); MS
(ESI): m/z = 368.1 [M+H]+; HRMS (ESI) m/z calcd for C18H32F3NOS
[M+H]+: 368.2230, found: 368.2223.
cmꢀ1
) mmax 754, 841, 1063, 1166, 1251, 1302, 1510, 1577, 2173,
2960, 3398; 1H NMR (400 MHz, CDCl3) d 0.24 (s, 9H), 2.03 (s,
2H), 3.83 (s, 3H), 6.93 (dt, J = 8.8, 3.2 Hz, 2H), 7.72 (d, J = 8.8 Hz,
2H); 13C NMR (100.6 MHz, CDCl3)
d 2.10, 57.64, 61.28 (q,
J = 30.3 Hz), 93.65, 105.63, 115.88, 126.72 (q, J = 284.2 Hz),
130.10, 131.30, 162.54; 19F NMR (376 MHz, CDCl3) d ꢀ79.36 (s,
3F); MS (ESI): m/z = 324.1 [M+Na]+; HRMS (ESI) m/z calcd for
C
14H18F3NOSi [M+Na]+: 324.1002, found: 324.0999.
4.2.20. (SS,R)-(+)-N-(3-(Trifluoromethyl)-1-(trimethylsilyl)non-
4.3.4. (R)-(+)-1-Cyclopropyl-3-(trifluoromethyl)non-1-yn-3-
1-yn-3-yl)-2-methylpropanesulfinamide 2r
White solid, yield 72%; mp 144 °C; ½a D24
¼ þ79:8 (c 1.0, CHCl3);
ꢃ
amine 3d
Pale yellow oil, yield 87%; ½a D29
¼ þ36:6 (c 0.42, CHCl3); IR (KBr,
ꢃ
IR (KBr, cmꢀ1
) mmax 854, 1055, 1106, 1176, 1261, 1462, 2189, 2954,
cmꢀ1
) mmax 708, 815, 919, 1168, 1260, 1370, 1459, 1635, 2247,
3112; 1H NMR (400 MHz, CDCl3) d 0.20 (s, 9H), 0.90 (t, J = 6.6 Hz,
3H), 1.23 (s, 9H), 1.29–1.39 (m, 6H), 1.57–1.71 (m, 2H), 1.89–
1.94 (m, 2H), 3.43 (s, 1H); 13C NMR (100.6 MHz, CDCl3) d ꢀ0.49,
14.00, 22.43, 22.52, 23.59, 29.08, 31.48, 34.65, 57.15, 61.13 (q,
J = 29.8 Hz), 94.66, 97.91, 124.32 (q, J = 286.1 Hz); 19F NMR
(376 MHz, CDCl3) d ꢀ77.87 (s, 3F); MS (ESI): m/z = 384.0 [M+H]+;
HRMS (ESI) m/z calcd for C17H32F3NOSSi [M+H]+: 384.1999, found:
384.1996.
2927, 3415; 1H NMR (400 MHz, CDCl3) d 0.66–0.72 (m, 2H),
0.73–0.80 (m, 2H), 0.88 (t, J = 6.6 Hz, 3H), 1.22–1.26 (m, 3H),
1.27–1.30 (m, 6H), 1.51–1.57 (m, 2H), 1.61 (s, 2H); 13C NMR
(100.6 MHz, CDCl3) d 1.64, 10.58, 10.61, 16.37, 24.89, 25.95,
31.61, 33.95, 37.88, 58.73 (q, J = 29.1 Hz), 74.03, 91.29, 128.02 (q,
J = 284.1 Hz); 19F NMR (376 MHz, CDCl3) d ꢀ81.10 (s, 3F); MS
(ESI): m/z = 248.1 [M+H]+; HRMS (ESI) calcd for m/z C13H20F3N
[M+H]+: 248.1621, found: 248.1631.
4.3. General experimental procedure for acidic cleavage of the
4.3.5. (R)-(+)-3-(Trifluoromethyl)-1-(trimethylsilyl)non-1-yn-3-
tert-butanesulfinyl groups to provide the corresponding
trifluoromethylated -propargylamine 3
a-
amine 3e
a
Pale yellow oil, yield 97%; ½a D27
¼ þ51:9 (c 0.45, CHCl3); IR (KBr,
ꢃ
cmꢀ1
) mmax 704, 761, 850, 1173, 1257, 1459, 1620, 2176, 2926,
To a solution of sulfinamides (1.0 mmol) in methanol (0.5 M)
was added HCl (0.5 mL, 4.0 M in 1,4-dioxane). The reaction mixture
was stirred at room temperature for 1 h and diluted with EtOAc
(15 mL) after which an NaOH aqueous solution (1 M) was carefully
added dropwise to adjust the pH of the mixture to 8. The organic
layer was removed and the aqueous layer was extracted with
EtOAc (15 mL ꢂ 2). The organic layers were combined and dried
over anhydrous Na2SO4, filtered, concentrated, and the residue
3410; 1H NMR (400 MHz, CDCl3) d 0.18 (s, 9H), 0.90 (t, J = 7.0 Hz,
3H), 1.25–1.53 (m, 8H), 1.58 (t, J = 6.0 Hz, 2H), 1.67 (s, 2H); 13C
NMR (100.6 MHz, CDCl3) d 0.00, 14.34, 22.81, 23.83, 29.50, 31.86,
35.56, 57.15 (q, J = 29.3 Hz), 90.68, 120.08, 128.54 (q,
J = 284.1 Hz); 19F NMR (376 MHz, CDCl3) d ꢀ80.80 (s, 3F); MS
(ESI): m/z = 280.0 [M+H]+; HRMS (ESI) m/z calcd for C13H24F3NSi
[M+H]+: 280.1703, found: 280.1714.

H. Xiao et al. / Tetrahedron: Asymmetry 21 (2010) 2949–2955
2955
Chem. 2001, 1449; (c) Crucianelli, M.; De Angelis, F.; Lazzaro, F.; Malpezzi, L.;
Volonterio, A.; Zanda, M. J. Fluorine Chem. 2004, 125, 573; (d) Lazzaro, F.;
Crucianelli, M.; De Angelis, F.; Frigerio, M.; Malpezzi, L.; Volonterio, A.; Zanda,
M. Tetrahedron: Asymmetry 2004, 15, 889.
Acknowledgments
The Shanghai Pujiang Program (09PJ1400800) and the Funda-
mental Research Funds for the Central Universities are greatly
acknowledged for funding this work.
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