Nucleophilic trifluoromethylation of imines using the CF3I/TDAE reagent

Article abstract of DOI:10.1021/jo050483v

The nucleophilic trifluoromethylation reagent derived from CF₃I and tetrakis(dimethylamino)-ethylene (TDAE) was found to be effective in addition to both N-tosyl aldimines and N-tolyl sulfinimines, the latter reaction exhibiting very good diastereoselectivity.

Full text of DOI:10.1021/jo050483v

Nucleophilic Trifluoromethylation of Imines Using the CF3I/TDAE
Reagent
Wei Xu and William R. Dolbier, Jr.*
Department of Chemistry, University of Florida, Gainesville, Florida 32611-7200
wrd@chem.ufl.edu
Received March 10, 2005
The nucleophilic trifluoromethylation reagent derived from CF3I and tetrakis(dimethylamino)-
ethylene (TDAE) was found to be effective in addition to both N-tosyl aldimines and N-tolyl
sulfinimines, the latter reaction exhibiting very good diastereoselectivity.
Introduction
tives with the idea of developing methods for preparing
trifluoromethylamines10 and, in particular, chiral tri-
fluoromethylamines,11,12 which had previously only been
synthesized from precursors (i.e., ketones) already bear-
ing a trifluoromethyl group.13-21 Indeed, use of CF3TMS
proved to be very effective for nucleophilic trifluoro-
methylation of N-tosyl aldimines and N-(2-methyl-2-
propane-sulfinyl)imines (Scheme 1), with the latter re-
actions exhibiting excellent diastereoselectivity.
An alternative approach to nucleophilic trifluoro-
methylation that was discovered in our laboratories in
2001 involves the generation of the required, sequestered
trifluoromethylcarbanion by two-electron reduction of
trifluoromethyliodide by tetrakis-(dimethylamino)ethyl-
ene (TDAE).22 The chemical reactivity of the CF3I/TDAE
reagent bears some similarities to that of CF3TMS, but,
in part because it does not involve the necessity for TMS
The trifluoromethyl substituent has long been recog-
nized for the beneficial impact that it can have upon the
biological activity of molecules.1,2 Although there are
many methods to directly or indirectly introduce a
trifluoromethyl group into a molecule,3 over the past
decade or so there has been an increase in the activity
directed toward methods involving “nucleophilic trifluoro-
methylation”.4-6 Because of the instability of directly
generated trifluoromethyl Grignards and lithium re-
agents,7 indirect methods utilizing in situ-generated
trifluoromethyl anion were required. Beginning with
Prakash’s report in 1989 of a very effective procedure
using Ruppert’s reagent (trifluoromethyltrimethylsilane)
to carry out nucleophilic trifluoromethylations,8 there has
been considerable effort expended in the development of
this and alternative methods for accomplishing such
chemistry.9
(10) Prakash, G. K. S.; Mandal, M.; Olah, G. A. Synlett. 2001, 77-
78.
There is a broad scope of substrates that have been
shown to undergo nucleophilic trifluoromethylation using
Ruppert’s reagent, and most recently Prakash and co-
workers have delved into its reactions with imine deriva-
(11) Prakash, G. K. S.; Mandal, M.; Olah, G. A. Angew. Chem., Int.
Ed. 2001, 40, 589-590.
(12) Prakash, G. K. S.; Mandal, M. J. Am. Chem. Soc. 2002, 124,
6538-6539.
(13) Pirkle, W. H.; Hanske, J. R. J. Org. Chem. 1977, 42, 2436-
2439.
(14) Wang, Y.; Mosher, H. S. Tetrahedron Lett. 1991, 32, 987-990.
(15) Soloshonok, V. A.; Ono, T. J. Org. Chem. 1997, 62, 3030-3031.
(16) Osipov, S. N.; Golubev, A. S.; Sewald, N.; Burger, K. Tetrahe-
dron Lett. 1997, 38, 5965-5966.
(1) Bhm, H.-J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Mller,
K.; Obst-Sander, U.; Stahl, M. ChemBioChem 2004, 5, 637-643.
(2) Jeschke, P. ChemBioChem 2004, 5, 570-589.
(3) McClinton, M. A.; McClinton, D. A. Tetrahedron 1992, 48, 6555-
6666.
(4) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97, 757-786.
(5) Prakash, G. K. S.; Mandal, M. J. Fluorine Chem. 2001, 112, 123-
131.
(17) Nelson, D. W.; Owens, J.; Hiraldo, D. J. Org. Chem. 2001, 66,
2572-2582.
(18) Gong, Y.; Kato, K. J. Fluorine Chem. 2002, 116, 103-107.
(19) Yong, K. H.; Chong, J. M. Org. Lett. 2002, 4, 4139-4142.
(20) Spanedda, M. V.; Ourevitch, M.; Crousse, B.; Begue, J.-P.;
Bonnet-Delpon, D. Tetrahedron Lett. 2004, 45, 5023-5025.
(21) Kochi, T.; Mukade, T.; Ellman, J. A. J. Synth. Org. Chem. Jpn.
2004, 62, 128-139.
(6) Singh, R. P.; Shreeve, J. M. Tetrahedron 2000, 56, 7613-7632.
(7) Burton, D. J.; Yang, Z.-Y. Tetrahedron 1992, 48, 189-275.
(8) Prakash, G. K. S.; Krishnamurthy, R.; Olah, G. A. J. Am. Chem.
Soc. 1989, 111, 393-395.
(22) At-Mohand, S.; Takechi, N.; Mdebielle, M.; Dolbier, W. R., Jr.
Org. Lett. 2001, 3, 4271-4273.
(9) Dolbier, W. R., Jr. Chim. Oggi 2003, 21, 66-69.
10.1021/jo050483v CCC: $30.25 © 2005 American Chemical Society
Published on Web 05/07/2005
J. Org. Chem. 2005, 70, 4741-4745
4741

Xu
SCHEME 1
SCHEME 4
SCHEME 5
SCHEME 2
TABLE 1. Trifluoromethylation of N-Tosylimines
R1R2CdNSO2Tol
2, yield (%)
compd
R1
R2
1a
1b
1c
Ph
H
H
86
84
84
81
78
76
62
54
4-CH3Ph
4-CH3OPh
4-FPh
H
1d
1e
H
4-ClPh
4-NO2Ph
PhCHdCH
Ph
H
SCHEME 3
1fa
1g
1hb
H
H
Ph
a In this case, the substrate was added to the reaction mixture
30 min after the mixing of CF3I and TDAE. b About 50% of starting
material was recovered in this reaction.
transfer as part of the mechanism, it also exhibits
significant differences such as in its ability to open cyclic
sulfates to produce â-trifluoromethyl alcohols.23 On the
other hand, CF3TMS appears to be more suitable for
reactions with substrates that bear readily enolizable
hydrogens (such as aliphatic aldehydes).
In our efforts to fully explore the scope and limitations
of the CF3I/TDAE reagent in nucleophilic trifluoromethyl-
ation chemistry, we considered it important to examine
its reactivity with imines of the type studied by Prakash
with CF3TMS. In the event, the end results were quite
similar, but some significant differences were also ob-
served. We report the results of this study in this paper.
modest to good yields for aryl systems by facilitating the
reaction of CF3TMS using TMS-imidazole.24
As Prakash showed, the reactivity of imines toward
nucleophilic trifluoromethylation can be significantly
enhanced by using N-tosylimines, with the p-toluene-
sulfonyl group being removed from the adduct by its
treatment with phenol and 48% HBr to give the respec-
tive primary amine products.10
Tosylimines are readily synthesized from the respective
aldehydes or ketones by a procedure developed by Ram
and Khan (Scheme 4).25
When a series of N-tosylimines, 1a-h, was allowed to
react with the trifluoromethyl anion reagent derived from
CF3I/TDAE in the usual manner, very good yields of the
trifluoromethylated adducts were obtained, as exempli-
fied in Scheme 5. The results for the entire series are
given in Table 1, and it can be seen that the reaction is
quite effective for aromatic N-tosylaldimines and still
satisfactory for the benzophenone N-tosylimine. In this
case, irradiation by a sun lamp does not enhance the
reaction. Unfortunately, the analogous reactions with
imines bearing aliphatic substituents on the imine carbon
did not produce the desired adducts. Such attempts
included the N-tosylimines of acetophenone, p-chloro-
acetophenone, cyclohexanone, and hexanal. In contrast,
aliphatic aldehydes had been reported to provide adducts
using Prakash’s CF3TMS methodology.10
Results and Discussion
Nucleophilic trifluoromethylation using the CF3I/TDAE
reagent is experimentally quite straightforward. Such
chemistry is exemplified by the reactions of aldehydes
and cyclic sulfates, where addition of 2.2 equiv of CF3I
to the appropriate dry solvent (i.e., DMF) containing the
substrate at -20 °C is followed by slow addition of 2.2
equiv of TDAE and warming to room temperature to give
products (Scheme 2). In the former example, irradiation
by a sun lamp was shown to enhance yields.
It has been demonstrated that, under such conditions,
a stabilized TDAE dication/trifluoromethyl anion “com-
plex” is generated by a two-electron transfer from TDAE
to CF3I (Scheme 3).22 This in situ reagent then can deliver
a trifluoromethyl anion to appropriate electrophilic sub-
strates.
Enantiopure sulfinimines have been demonstrated to
be versatile chiral imine building blocks for the asym-
metric synthesis of amines.11 There are a number of
reasons for this, including the ability of the sulfinyl group
to enhance nucleophilic addition to the CdN double bond,
its ability to provide superior stereocontrol, and not to
Simple alkyl- or aryl-substituted imines are relatively
unreactive toward nucleophilic trifluoromethylation, al-
though Blazejewski and co-workers were able to obtain
(24) Blazejewski, J. C.; Anselmi, E.; Wilmshurst, M. P. Tetrahedron
Lett. 1999, 40, 5475-5478.
(25) Ram, R. N.; Khan, A. A. Synth. Commun. 2001, 841-846.
(23) Takechi, N.; Ait-Mohand, S.; Medebielle, M.; Dolbier, W. R.,
Jr. Org. Lett. 2002, 4, 4671-4672.
4742 J. Org. Chem., Vol. 70, No. 12, 2005

Nucleophilic Trifluoromethylation of Imines
SCHEME 6
SCHEME 8
SCHEME 7
effective for addition to both N-tosyl- and N-tolylsulfin-
aldimines and thus provides a viable synthetic alterna-
tive to the use of CF3TMS in the synthesis of trifluoro-
methylamines. The N-tosylimine reaction appears to be
limited to use with nonenolizable aldimines, and the
diastereoselectivities of the N-tolylsulfinimine reaction,
while good, fall short of those observed by Prakash in
the CF3TMS-derived trifluoromethylation of (2-methyl-
2-propane)sulfinaldimines.
TABLE 2. Trifluoromethylation of N-Tolylsulfinimines
R1C2HdNSO2Tol
compd
R
dr
4, yield (%)
3a
3b
3c
3d
3e
3f
3g
3h
3i
Ph
87:13
86:14
82:18
85:15
88:12
72:28
88:12
94:6
66
4-CH3Ph
4-CH3OPh
4-FPh
73
71
69
4-CF3Ph
n-C6H13
4-ClPh
1-naphthyl
C(CH3)3
74
48
Experimental Section
67
42
1H and 19F NMR spectra were recorded in CDCl3 using
tetramethylsilane (TMS) and CFCl3 as internal standards,
respectively. TDAE was prepared by a published procedure
(with some modification);29 N-tosyl aldimines 1a-g were
prepared according to the previous literature.25 Sulfinimines
3a-e, 3g, and 3h were prepared according to Davis’s method,26
and 3f was prepared by Ruano’s Procedure.30 S-(+)-2,4,
6-Trimethylphenyl sulfinamide was prepared following Se-
nannayake’s method,27 and 5 was prepared by a published
procedure.28
General Procedure for Trifluoromethylation of
N-Tosyl Aldimines. Into a three-necked flask equipped with
a dry ice reflux condenser were added 10 mL of anhydrous
DMF and the N-tosylimine (1 mmol). The system was degassed
and filled with dry nitrogen under a balloon. The solution was
cooled to -30 °C, and TDAE (2.2 mmol) was added. After
stirring for 15 min, CF3I (2.2 mmol) was bubbled into the
mixture. The solution was vigorously stirred at -30 °C for
30 min and then allowed to warm slowly to room temperature.
The mixture was stirred overnight, after which it was quenched
with 2 N hydrochloride acid solution. The resulting aqueous
mixture was extracted with dichloromethane (three times); the
extract washed with brine (three times) and then dried over
Na2SO4. The solvent was removed, and the crude product was
purified by silica gel chromatography (ethyl acetate/hexane )
1:5) to give the trifluoromethylated product.
no product
mention its easy removal under mild acid conditions.
N-p-Tolylsulfinylimines are easily prepared from the
respective aldehydes or ketones and commercially avail-
able (1R,2S,5R)-(-)-menthyl (S)-p-toluenesulfinate by a
procedure developed by Davis and co-workers (Scheme
6).26 According to Davis, p-toluenesulfinimides are much
more convenient chiral auxiliaries to make than are
N-tert-butylsulfinimides.
Indeed, when nucleophilic trifluoromethylation of
p-toluenesulfinimides 3a-f was carried out with the
CF3- reagent derived from CF3I/TDAE, very good yields
and diastereoselectivities were observed for a wide
variety of substrates (Scheme 7, Table 2), including, in
this case, one derived from an aliphatic aldehyde (4f).
In hopes of increasing the diastereoselectivity of the
reaction, the tolyl group was replaced by a mesityl group.
This necessitated the use of an alternative procedure for
the preparation of sulfinimine 5 from S-(+)-2,4,6-tri-
methylphenyl sulfonamide (Scheme 8).27,28
Unfortunately, only a modest increase in diastereo-
selectivity was observed as a result of using the mesityl
rather than the tosyl derivative.
In an attempt to compare the diastereoselectivity of
our reagent directly with that of CF3TMS, the (2-methyl-
2-propane)sulfinimine derivative of benzaldehyde was
examined using our CF3I/TDAE reagent. Unfortunately,
no significant amount of products deriving from nucleo-
philic trifluoromethylation was able to be detected in this
reaction.
4-Methyl-N-(2,2,2-trifluoro-1-phenyl-ethyl)-benzene-
sulfonamide, 2a:10 pale white solid, yield 86%; mp 155-
156 °C; 1H NMR δ 2.37 (s, 3H), 4.92 (q, J ) 7.5 Hz, 1H), 5.23
(d, J ) 9.3 Hz, 1H), 7.15-7.18 (m, 4H), 7.28-7.33 (m, 3H),
7.60 (d, J ) 8.1 Hz, 2H); 19F NMR δ -74.3 (d, J ) 6.5 Hz, 3F);
MS (EI) m/z 329 (M+), 328 (M+ - H), 260 (M+ - CF3), 174
(M+ - 4-CH3-C6H4SO2), 155 (M+ - C6H5CHCF3NH), 91
(C6H5CH2+). Anal. Calcd for C15H14F3NO2S: C, 54.70; H, 4.28;
N, 4.25. Found: C, 54.72; H, 4.21; N, 4.18.
4-Methyl-N-[2,2,2-trifluoro-1-(4-methyl-phenyl)-ethyl]-
benzenesulfonamide, 2b: pale white solid, yield 84%;
mp 181-182 °C; 1H NMR δ 2.31 (s, 3H), 2.37 (s, 3H), 4.87
(q, J ) 7.5 Hz, 1H), 5.21 (d, J ) 9.0 Hz, 1H), 7.08 (s, 4H), 7.17
(d, J ) 8.1 Hz, 2H), 7.61 (d, J ) 8.1 Hz, 2H); 19F NMR δ -74.4
Conclusion
In conclusion, the nucleophilic trifluoromethylation
reagent derived from CF3I/TDAE has proved to be
(d, J ) 6.5 Hz, 3F); MS (EI) m/z 342 (M+ - H), 274 (M+
-
(26) Davis, F. A.; Zhang, Y.; Andemichael, Y.; Fang, T.; Fanelli, D.
L.; Zhang, H. J. Org. Chem. 1999, 64, 1403-1406.
(27) Han, Z. X.; Krishnamurthy, D.; Grover, P.; Fang, Q. K.;
Senanayake, C. H. J. Am. Chem. Soc. 2002, 124, 7880-7881.
(28) Davis, F. A.; Ramachandar, T.; Wu, Y. Z. J. Org. Chem. 2003,
68, 6894-6898.
(29) Pruett, R. L.; Barr, J. T.; Rapp, K. E.; Bahner, C. T.; Gibson, J.
D.; Lafferty, H. L. J. Am. Chem. Soc. 1950, 72, 3646-3650.
(30) Ruano, J. L. G.; Aleman, J.; Soriano, J. F. Org. Lett. 2003, 5,
677-680.
J. Org. Chem, Vol. 70, No. 12, 2005 4743

Xu
CF3), 188 (M+ - 4-CH3-C6H4SO2), 155 (M+ - 4-CH3C6H5-
CHCF3NH), 91 (C6H5CH2+). Anal. Calcd for C16H16F3NO2S: C,
55.97; H, 4.70; N, 4.08. Found: C, 55.49; H, 4.70; N, 4.07.
4-Methyl-N-[2,2,2-trifluoro-1-(4-methoxy-phenyl)-eth-
yl]-benzenesulfonamide, 2c:10 pale white solid, yield 84%;
mp 152-153 °C; 1H NMR δ 2.37 (s, 3H), 3.77 (s, 3H), 4.85
(q, J ) 8.4 Hz, 1H), 5.31 (d, J ) 8.7 Hz, 1H), 6.77 (d, J ) 8.7
Hz, 2H), 7.10 (d, J ) 8.7 Hz, 2H), 7.18 (d, J ) 8.1 Hz, 2H),
7.60 (d, J ) 8.1 Hz, 2H); 19F NMR δ -74.6 (d, J ) 6.2 Hz, 3F);
MS (EI) m/z 359 (M+), 290 (M+ - CF3), 204 (M+ - 4-CH3-C6H4-
SO2), 155 (M+ - 4-CH3O-C6H5CHCF3NH), 91 (C6H5CH2+);
Anal. Calcd for C16H16F3NO3S: C, 53.48; H, 4.49; N, 3.90.
Found: C, 53.36; H, 4.48; N, 3.81
times), and the extract was washed with brine (three times)
and dried over Na2SO4. The solvent was removed, and the
crude product was purified by silica gel chromatography (ethyl
acetate/hexane ) 1:5) to give the trifluoromethylated product
as a mixture of diastereomers. There was no indication of a
significant separation of the diastereomers during the chro-
matography.
1
4a: pale white solid, yield 66%; mp 107-108 °C; H NMR
δ 2.31 (s, 0.87 × 3H), 2.37 (0.13 × 3H), 4.57 (d, J ) 6.6 Hz,
0.87 × 1H), 4.66-4.77 (m, 0.13 × 2H), 4.85 (q, J ) 7.2 Hz,
0.87 × 1H), 7.15-7.25 (m, 0.87 × 7H), 7.36-7.40 (m, 0.13 ×
7H), 7.47 (d, J ) 8.1 Hz, 0.87 × 2H), 7.55 (d, J ) 8.1 Hz,
0.13 × 2H); 19F NMR δ -74.2 (d, J ) 6.2 Hz, 0.13 × 3F), -74.4
(d, J ) 8.4 Hz, 0.87 × 3F); MS (EI) m/z 313 (M+), 265 (M+
-
4-Methyl-N-[2,2,2-trifluoro-1-(4-fluoro-phenyl)-ethyl]-
SO), 174 (M+ - SOC6H4-4-CH3), 139 (+SOC6H4-4-CH3), 91
(C6H5CH2+), 77 (C6H5+); HRMS (EI) calcd for C15H14F3NOS
(M+) 313.0748, found 313.0748. Anal. Calcd for C15H14F3-
NOS: C, 57.50; H, 4.50; N, 4.47. Found: C, 57.29; H, 4.51; N,
4.35.
benzenesulfonamide 2d: pale white solid, yield 81%;
1
mp 182-183 °C; H NMR δ2.38 (s, 3H), 4.90 (q, J ) 8.4 Hz,
1H), 5.50 (d, J ) 9.6 Hz, 1H), 6.92-6.99 (m, 2H), 7.17-7.20
(m, 4H), 7.60 (d, J ) 8.1 Hz, 2H); 19F NMR δ -74.5 (d, J )
6.4 Hz, 3F), -111.8 (s, 1F); MS (EI) m/z 347 (M+), 346 (M+
H), 278 (M+ - CF3), 192 (M+ - 4-CH3-C6H4SO2), 155 (M+
-
-
1
4b: pale white solid, yield 73%; mp 102-103 °C; H NMR
4-FC6H5CHCF3NH), 91 (C6H5CH2+). Anal. Calcd for C15H13F4-
NO2S: C, 51.87; H, 3.77; N, 4.03. Found: C, 51.82; H, 3.73;
N, 3.92.
δ 2.33 (s, 0.86 × 3H), 2.40 (s, 3H), 2.44 (s, 0.14 × 3H), 4.56
(d, J ) 6.9 Hz, 0.86 × 1H), 4.69-4.72 (m, 0.14 × 1H), 4.78
(q, J ) 7.2 Hz, 0.14 × 1H), 4.89 (q, J ) 7.2 Hz, 0.86 × 1H),
7.12-7.20 (m, 0.86 × 4H), 7.25 (d, J ) 6.6 Hz, 2H), 7.36
(t, J ) 7.2 Hz, 0.14 × 4H), 7.61 (d, J ) 8.4 Hz, 0.86 × 2H),
7.55 (d, J ) 7.8 Hz, 0.14 × 2H); 19F NMR δ -74.3 (d, J )
8.5 Hz, 0.14 × 3F), -74.4 (d, J ) 8.5 Hz, 0.86 × 3F); MS (EI)
m/z 327 (M+), 278 (M+ - SO), 188 (M+ - SOC6H4-4-CH3), 139
(+SOC6H4-4-CH3), 91 (C6H5CH2+); HRMS (EI) calcd for C16H16F3-
NOS (M+) 327.0905, found 327.0891. Anal. Calcd for C16H16F3-
NOS: C, 58.70; H, 4.93; N, 4.28. Found: C, 58.35; H, 4.88; N,
4.21.
4-Methyl-N-[2,2,2-trifluoro-1-(4-chloro-phenyl)-ethyl]-
benzenesulfonamide, 2e:10 pale white solid, yield 78%;
1
mp 202-203 °C; H NMR δ 2.39 (s, 3H), 4.90 (q, J ) 7.8 Hz,
1H), 5.43 (d, J ) 7.2 Hz, 1H), 7.11-7.25 (m, 6H), 7.60 (d, J )
8.4 Hz, 2H); 19F NMR δ - 74.4 (d, J ) 6.5 Hz, 3F); MS (EI)
m/z 365 (M+ + 2), 363 (M+), 362 (M+ - H), 294 (M+ - CF3),
208 (M+ - 4-CH3-C6H4SO2), 155 (M+ - 4-ClC6H5CHCF3NH),
91 (C6H5CH2+). Anal. Calcd for C15H13ClF3NO2S: C, 49.52; H,
3.60; N, 3.85. Found: C, 49.36; H, 3.52; N, 3.76.
4c: pale white solid, yield 71%; mp 87-88 °C; 1H NMR
δ 2.38 (s, 0.82 × 3H), 2.43 (s, 0.18 × 3H), 3.78 (s, 0.82 × 3H),
3.83 (s, 0.18 × 3H), 4.59 (d, J ) 6.6 Hz, 0.82 × 1H), 4.70-4.80
(m, 0.18 × 2H), 4.87 (q, J ) 7.5 Hz, 0.82 × 1H), 6.80-6.85
(m, 0.82 × 2H), 6.92-6.97 (m, 0.18 × 2H), 7.12-7.42 (m, 4H),
7.53 (d, J ) 8.1 Hz, 0.82 × 2H), 7.60 (d, J ) 8.1 Hz, 0.18 ×
2H); 19F NMR δ -74.47 (d, J ) 8.5 Hz, 0.18 × 3F), -74.52
(d, J ) 8.5 Hz, 0.82 × 3F); HRMS (ESI) calcd for C16H16F3-
NOS (M+ + Na) 366.0751, found 366.0744. Anal. Calcd for
C16H16F3NO2S: C, 55.97; H, 4.70; N, 4.08. Found: C, 55.65;
H, 4.88; N, 4.41.
4-Methyl-N-[2,2,2-trifluoro-1-(4-nitro-phenyl)-ethyl]-
benzenesulfonamide, 2f: yellow solid, yield 76%; mp 166-
167 °C; 1H NMR δ 2.38 (s, 3H), 5.05 (q, J ) 8.7 Hz, 1H), 5.65
(d, J ) 8.7 Hz, 1H), 7.20 (d, J ) 8.1 Hz, 2H), 7.42 (d, J )
9.0 Hz, 2H), 7.62 (d, J ) 8.4 Hz, 2H), 8.14 (d, J ) 8.7 Hz, 2H);
19F NMR δ -73.9 (d, J ) 6.5 Hz, 3F); MS (EI) m/z 374 (M+),
373 (M+ - H), 305 (M+ - CF3), 219 (M+ - 4-CH3-C6H4SO2),
155 (M+ - 4-NO2C6H5CHCF3NH), 91 (C6H5CH2+). Anal. Calcd
for C15H13F3N2O4S: C, 48.13; H, 3.50; N, 7.48. Found: C, 47.74;
H, 3.50; N, 7.16.
4-Methyl-N-(1,1,1-trifluoro-4-phenylbut-3-en-2-yl)-ben-
zenesulfonamide, 2g:10 pale white solid, yield 62%; mp 119-
120 °C; 1H NMR δ 2.36 (s, 3H), 4.58 (q, J ) 8.7 Hz, 1H), 4.96
(d, J ) 9.3 Hz, 1H), 5.90 (d d, J ) 17.1, 8.1 Hz, 1H), 6.51
(d, J ) 15.9 Hz, 1H), 7.21-7.33 (m, 7H), 7.75 (d, J ) 8.1 Hz,
2H); 19F NMR δ -75.8 (d, J ) 6.5 Hz, 3F); MS (EI) m/z 355
(M+), 354 (M+ - H), 286 (M+ - CF3), 200 (M+ - 4-CH3-C6H4-
SO2), 155 (M+ - 4-FC6H5CHCF3NH), 91 (C6H5CH2+). Anal.
Calcd for C17H16F3NO2S: C, 57.46; H, 4.54; N, 3.94. Found:
C, 57.59; H, 4.43; N, 3. 88.
4-Methyl-N-(2,2,2-trifluoro-1,1-diphenyl-ethyl]-benze-
nesulfonamide, 2h: pale white solid, yield 54%; mp 184-
185 °C; 1H NMR δ 2.37 (s, 3H), 5.72 (s, 1H), 7.05 (d, J )
8.1 Hz, 2H), 7.23-7.34 (m, 12H); 19F NMR δ -69.9 (s, 3F);
MS (EI) m/z 405 (M+), 404 (M+ - H), 336 (M+ - CF3), 250
(M+ - 4-CH3-C6H4SO2), 155 (M+ - (C6H5)2CCF3NH), 91 (C6H5-
CH2+). Anal. Calcd for C21H18F3NO2S: C, 62.21; H, 4.47; N,
3.45. Found: C, 62.05; H, 4.44; N, 4.40.
General Procedure for Trifluoromethylation of Sulfin-
imines. Into a three-necked flask equipped with a dry ice
reflux condenser were added 10 mL of anhydrous DMF and
S-(+)-sulfinimine (1 mmol). The system was degassed and
filled with dry nitrogen with a balloon. The solution was cooled
to - 30 °C, and TDAE (2.2 mmol) was added. After the reaction
was stirred for 15 min, CF3I (2.2 mmol) was bubbled into the
mixture. The solution was vigorously stirred at -30 °C for
30 min and then warmed slowly to room temperature. The
mixture was stirred overnight, and the reaction was quenched
with saturated ammonia chloride solution. The resulting
aqueous mixture was extracted with dichloromethane (three
4d: pale white solid, yield 69%; mp 92-93 °C; 1H NMR
δ 2.37 (s, 0.85 × 3H), 2.43 (s, 0.15 × 3H), 4.62 (d, J ) 6.6 Hz,
0.85 × 1H), 4.70-4.80 (m, 0.15 × 2H), 4.91 (q, J ) 7.8 Hz,
0.85 × 1H), 6.95-7.01 (m, 0.85 × 2H), 7.09-7.15 (m, 0.85 ×
2H), 7.20-7.36 (m, 4H), 7.49 (d, J ) 8.1 Hz, 0.85 × 2H), 7.59
(d, J ) 8.4 Hz, 0.15 × 2H); 19F NMR δ -74.3 (d, J ) 8.5 Hz,
0.14 × 3F), -74.4 (d, J ) 8.5 Hz, 0.86 × 3F); MS (EI) m/z 331
(M+), 283 (M+ - SO), 192 (M+ - SOC6H4-4-CH3), 139
(+SOC6H4-4-CH3), 91 (C6H5CH2+); HRMS (EI) calcd for C15H13F4-
NOS (M+) 331.0654, found 331.0650. Anal. Calcd for C15H13F4-
NOS: C, 54.38; H, 3.95; N, 4.23. Found: C, 54.28; H, 3.83; N,
4.11.
4e: pale white solid, yield 74%; mp 96-97 °C; 1H NMR
δ 2.35 (s, 0.88 × 3H), 2.45 (s, 0.12 × 3H), 4.81 (d, J ) 6.3 Hz,
1H), 5.00 (q, J ) 8.4 Hz, 1H), 7.16 (d, J ) 8.1 Hz, 2H), 7.34
(d, J ) 8.4 Hz, 2H), 7.46 (m, 0.88 × 2H), 7.52 (d, J ) 8.1 Hz,
0.88 × 2H), 7.62 (m, 0.12 × 2H), 7.71 (d, J ) 7.8 Hz, 0.12 ×
2H); 19F NMR δ -63.28 (s, 0.12 × 3F), -63.32 (s, 0.88 × 3F),
-73.9 (d, J ) 6.2 Hz, 0.12 × 3F), -74.0 (d, J ) 6.9 Hz, 0.88 ×
3F); MS (EI) m/z 381 (M+), 333 (M+ - SO), 245 (M+ - SOC6H4-
4-CH3), 139 (+SOC6H4-4-CH3), 91 (C6H5CH2+); HRMS (EI)
calcd for C16H13F6NOS (M+) 381.0622, found 327.0624. Anal.
Calcd for C16H13F6NOS: C, 50.39; H, 3.44; N, 3.67. Found: C,
50.12; H, 3.51; N, 3.50.
4f: pale yellow liquid that crystallizes upon standing, yield
48%; mp 66-67 °C; 1H NMR (CDCl3) δ 0.88 (t, J ) 7.2 Hz,
3H), 1.28 (s, 6H), 1.45-1.87 (m, 4H), 2.41 (s, 3H), 2.44 (s, 0.14
× 3H), 3.58-3.66 (m, 0.28 × 1H), 3.76-3.83 (m, 0.72 × 1H),
4.02 (d, J ) 7.8 Hz, 0.72 × 1H), 4.34 (d, J ) 9.0 Hz, 0.28 ×
4744 J. Org. Chem., Vol. 70, No. 12, 2005

Nucleophilic Trifluoromethylation of Imines
1H),7.28-7.32 (m, 2H), 7.56-7.61 (m, 2H); 19F NMR δ -75.4
(d, J ) 6.2 Hz, 0.28 × 3F), -76.8 (d, J ) 6.5 Hz, 0.72 × 3F);
MS (EI) m/z 322 (M+ + H), 321 (M+), 273 (M+ - SO), 182
(M+ - SOC6H4-4-CH3), 139 (+SOC6H4-4-CH3); HRMS (EI) calcd
for C15H23F3NOS (M+ + H) 322.1452, found 322.1461.
1H), 7.03 (d, J ) 8.4 Hz, 2H), 7.40-7.60 (m, 8H), 7.82-7.92
(m, 4H); 19F NMR δ -73.2 (d, J ) 7.6 Hz, 0.94 × 3F), -73.9
(d, J ) 7.1 Hz, 0.06 × 3F); HRMS (ESI) calcd for C19H16F3-
NOS (M+ + Na) 386.0802, found 386.0744.
6: pale white solid, yield 57%; 1H NMR δ 2.29 (s, 3H), 2.51
(s, 6H), 4.68 (d, J ) 9.0 Hz, 0.90 × 1H), 4.82 (d, J ) 8.7 Hz,
0.10 × 1H), 4.94 (q, J ) 6.3 Hz, 0.90 × 1H), 4.97-5.04
(m, 0.10 × 1H), 6.85 (s, 2H), 7.41-7.48 (m, 5H); 19F NMR
δ -74.3 (d, J ) 6.2 Hz, 0.90 × 3F), -74.5 (d, J ) 6.2 Hz,
0.10 × 3F.
4g: pale white solid, yield 67%; mp 90-91 °C; 1H NMR
δ 2.36 (s, 0.88 × 3H), 2.43 (s, 0.12 × 3H), 4.56 (d, J ) 6.9 Hz,
0.88 × 1H), 4.74 (t, J ) 6.9 Hz, 0.12 × 1H), 4.86 (q, J )
7.5 Hz, 0.88 × 1H), 4.99 (d, J ) 7.2 Hz, 0.88 ×1H), 7.15-7.59
(m, 8H); 19F NMR δ -74.1 (d, J ) 8.5 Hz, 0.12 × 3F), -74.3
(d, J ) 9.0 Hz, 0.88 × 3F); MS (EI) m/z 347 (M+), 299 (M+
-
SO), 208 (M+ - SOC6H4-4-CH3), 139 (+SOC6H4-4-CH3), 91
(C6H5CH2+); HRMS (EI) calcd for C15H13ClF3NOS (M+) 347.0358,
found 347.0350. Anal. Calcd for C15H13ClF3NOS: C, 51.80; H,
3.77; N, 4.03. Found: C, 51.56; H, 3.66; N, 3.84.
Acknowledgment. Support of this work in part by
the National Science Foundation is acknowledged with
thanks.
1
4h: pale white solid, yield 42%; mp 109-110 °C; H NMR
δ 2.23 (s, 3H), 4.88 (d, J ) 5.7 Hz, 1H), 5.80 (q, J ) 7.2 Hz,
JO050483V
J. Org. Chem, Vol. 70, No. 12, 2005 4745