E
C. Guissart et al.
Letter
Synlett
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Tetrahedron 2012, 68, 6665.
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Hiyama, T. Synlett 2007, 1163. (b) Sakamoto, T.; Takahashi, K.;
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(20) Typical Procedure for the Synthesis of γ-Trifluoromethylated
Allenamide 3 from Trifluoromethylated Alkyne 2
The reaction of 2a is representative. To a stirred solution of the
trifluoromethylated propargyl amide 2 (0.15 mmol) in THF
(2.40 mL) was added NaOH (1.20 mL, 1.20 mmol, 1 M in H2O, 8
equiv), and the reaction was stirred at 40 °C for 24 h. After com-
pletion of the reaction, the crude mixture was quenched with a
sat. aq NH4Cl solution, and the aqueous layer was extracted
with Et2O (three times). The combined organic layers were
washed with water (twice), brine, dried with MgSO4, filtered,
and concentrated under vacuum. The crude was purified by
flash column chromatography on silica gel to afford the desired
γ-trifluoromethylated allenamide 3.
(13) (a) Burton, D. J.; Hartgraves, G. A.; Hsu, J. Tetrahedron Lett. 1990,
31, 3699. (b) Bouillon, J.-P.; Maliverney, C.; Merenyi, R.; Viehe,
H. G. J. Chem. Soc., Perkin Trans. 1 1991, 2147. (c) Zhao, T. S. N.;
Szabó, K. J. Org. Lett. 2012, 14, 3966. (d) Miyake, Y.; Ota, S.-i.;
Shibata, M.; Nakajima, K.; Nishibayashi, Y. Chem. Commun.
2013, 49, 7809. (e) Ji, Y.-L.; Kong, J.-J.; Lin, J.-H.; Xiao, J.-C.; Gu,
Y.-C. Org. Biomol. Chem. 2014, 12, 2903. (f) Ambler, B. R.; Peddi,
S.; Altman, R. A. Synthesis 2014, 46, 1938. (g) Ambler, B. R.;
Peddi, S.; Altman, R. A. Org. Lett. 2015, 17, 2506. (h) Ji, Y.-L.; Luo,
J.-J.; Lin, J.-H.; Xiao, J.-C.; Gu, Y.-C. Org. Lett. 2016, 18, 1000.
(14) Tresse, C.; Guissart, C.; Schweizer, S.; Bouhoute, Y.; Chany, A.-C.;
Goddard, M.-L.; Blanchard, N.; Evano, G. Adv. Synth. Catal. 2014,
356, 2051.
tert-Butyl Dodecyl(4,4,4-trifluorobuta-1,2-dien-1-yl)carba-
mate (3a)
This product was obtained from tert-butyl dodecyl(4,4,4-trifluo-
robut-2-yn-1-yl)carbamate (2a, 50 mg, 0.13 mmol) to afford the
desired product 3a (46 mg, 0.12 mmol, 92%) as a colorless oil.
Solvent system for flash chromatography: cyclohexane–EtOAc–
Et3N (100:1:1). 1H NMR (300 MHz, CDCl3): δ = 7.65 and 7.47 (br
s, 1 H, rot.), 5.95 (app. quint, J = 5.5 Hz, 1 H), 3.28 (t, J = 6.5 Hz, 2
H), 1.55–1.45 (m, 11 H), 1.25 (s, 18 H), 0.88 (t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 199.9 and 198.4 (br s, rot.),
152.7 and 152.0 (br s, rot.), 121.7 (q, J = 271.3 Hz), 107.1 (br s),
95.4 (q, J = 39.6 Hz), 82.0 (br s), 46.2 and 45.7 (rot.), 32.1, 29.8 (2
C), 29.69, 29.66, 29.5, 29.4, 28.3 (3 C), 27.4 (br s), 26.8, 22.8,
14.2. 19F NMR (376 MHz, CDCl3): δ = –63.1 (dd, J = 5.3, 3.3 Hz, 3
F). IR (ATR): νmax = 2935, 2856, 1707, 1467, 1370, 1283, 1141,
870 cm–1. HRMS (APCI): m/z calcd for C21H36F3NaNO4 [M + Na]+:
414.2590; found: 414.2588.
(15) Navarro-Vázquez, A. Beilstein J. Org. Chem. 2015, 11, 1441.
(16) Typical Procedure for the Synthesis of Trifluoromethylated
Alkyne 2 from Terminal Alkyne 1
The reaction of 1a is representative. A 50 mL round-bottom
flask was charged with CuI (143 mg, 0.75 mmol, 1.5 equiv),
K2CO3 (207 mg, 1.5 mmol, 3.0 equiv), TMEDA (112 μL, 0.75
mmol, 1.5 equiv), and DMF (2.3 mL). The resulting deep blue
mixture was vigorously stirred at room temperature under air
atmosphere for 20 min. TMSCF3 (148 μL, 1.00 mmol, 2.0 equiv)
was added, and the resulting deep green mixture was stirred for
an additional 15 min under air atmosphere, then cooled to 0 °C.
A solution of terminal alkyne 1 (0.50 mmol, 1 equiv) and
TMSCF3 (148 μL, 1.00 mmol, 2.0 equiv) in DMF (2.3 mL), previ-
ously cooled to 0 °C, was then added in one portion. The reac-
tion mixture was stirred at 0 °C for 30 min, under air atmo-
sphere, and allowed to warm to room temperature and stirred
for 24 h. At the end of the reaction, H2O was added and the
aqueous layer was extracted with Et2O (three times). The com-
bined organic layers were washed with H2O (three times), brine,
dried over MgSO4, filtered, and concentrated under vacuum.
The crude product was then purified by flash column chroma-
tography on silica gel to afford the desired trifluoromethylated
alkyne 2.
t-Butyl Dodecyl(4,4,4-trifluorobut-2-yn-1-yl)carbamate (2a)
This product was obtained following the general procedure
from tert-butyl dodecyl(prop-2-yn-1-yl)carbamate (1a, 250 mg,
0.77 mmol) to afford the desired product (226 mg, 0.58 mmol,
75%) as a yellow oil. Solvent system for flash chromatography:
pentane–Et2O (9:1). 1H NMR (300 MHz, CDCl3): δ = 4.28–3.95
(m, 2 H), 3.28 (t, J = 7.3 Hz, 2 H), 1.58–1.50 (m, 2 H), 1.47 (s, 9 H),
1.34–1.21 (m, 18 H), 0.88 (t, J = 6.4 Hz, 3 H). 13C NMR (100 MHz,
CDCl3): δ = 155.0 (br s), 114.0 (q, J = 257.1 Hz), 84.5 (br s), 80.8,
70.4 (q, J = 50.9 Hz), 47.3 (br s), 36.5 and 35.7 (br s, rot.), 32.0,
29.77, 29.75, 29.70 (2 C), 29.5, 29.4, 28.4 (3 C), 28.2, 26.8, 22.8,
14.2. 19F NMR (376 MHz, CDCl3): δ = –51.3 (br s, 3 F). IR (ATR):
(21) Sulfonamides were not tolerated in this process, the highly elec-
trophilic tosyl iminium intermediate being hydrolyzed over
time. This is a clear indication that a one-pot trifluoromethyla-
tion–isomerization sequence is feasible, although such
process was not systematically explored in this work.
a
(22) We currently do not have a sound explanation for this lack of
reactivity. Along the same lines, it was noticed that the oxida-
tive copper-mediated trifluoromethylation reaction of terminal
alkynes was inhibited with certain classes of substrates such as
N-propargyl phthalimide or substrates possessing a phenyl
group in the propargylic position.
(23) Shen, L.; Hsung, R. P. Org. Lett. 2005, 7, 775.
(24) (a) Krause, N.; Winter, C. Chem. Rev. 2011, 111, 1994.
(b) Hashmi, A. S. K.; Schwarz, L.; Choi, J.-H.; Frost, T. M. Angew.
Chem. Int. Ed. 2000, 39, 2285.
(25) (a) Manzo, A. M.; Perboni, A. D.; Broggini, G.; Rigamonti, M. Tet-
rahedron Lett. 2009, 50, 4696. (b) Singh, S.; Elsegood, M. R. J.;
Kimber, M. C. Synlett 2012, 23, 565. (c) De Sousa Fonseca, F. C.;
Araujo, F. M.; Nagem, T. J.; de Oliveira, T. T.; Roque, D.; Correia,
C.; Taylor, J. G. Synth. Commun. 2013, 43, 758. (d) Bernal-Albert,
P.; Faustino, H.; Gimeno, A.; Asensio, G.; Mascarenas, J. L.;
Lopez, F. Org. Lett. 2014, 16, 6196. (e) Slater, N. H.; Brown, N. J.;
Elsegood, M. R. J.; Kimber, M. C. Org. Lett. 2014, 16, 4606.
(26) For related gold-catalyzed anellations, see: (a) Pflästerer, D.;
Dolbundalchok, P.; Rafique, S.; Rudolph, M.; Rominger, F.;
Hashmi, A. S. K. Adv. Synth. Catal. 2013, 355, 1383. (b) Pflästerer,
D.; Rettenmeier, E.; Schneider, S.; de Las Heras Ruiz, E.;
Rudolph, M.; Hashmi, A. S. K. Chem. Eur. J. 2014, 20, 6752.
ν
max = 2924, 2859, 2283, 1696, 1457, 1402, 1283, 1152, 870, 750
cm–1. HRMS (APCI): m/z calcd for C21H36F3NaNO2 [M + Na]+:
414.2590; found: 414.2583.
(17) Huang, J.; Xiong, H.; Hsung, R. P.; Rameshkumar, C.; Mulder, J.
A.; Grebe, T. P. Org. Lett. 2002, 4, 2417.
(18) Liu, H.; Leow, D.; Huang, K.-W.; Tan, C.-H. J. Am. Chem. Soc.
2009, 131, 7212.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F