Please do not adjust margins
Organic & Biomolecular Chemistry
Page 8 of 10
ARTICLE
Journal Name
tert-Butyl 4-(4,4-difluoropentanoyl)piperidine-1-carboxylate (376 MHz, CDCl3): δ = −220.5 (tt, JHF = 47.3, 27.V0iewHAzr)t.iclHe ORnMlinSe
+
+
DOI: 10.1039/C7OB00680B
(5c). Isolated yield: 66% (100 mg). Column chromatography (AJSESI) calcd. for C14H24FNO3Na [M+Na] 296.1632, found m/z
eluent – petroleum ether/ethyl acetate (15:1 – 2:1). Starting 296.1635.
material 1f was recovered in 12% yield (14 mg). Н NMR (400
1
MHz, CDCl3): δ = 4.11 (br s, 2H), 2.78 (m, 2H), 2.68 (m, 2H), 2.50
(tt, J = 11.4, 3.7 Hz, 1H), 2.15 (tt, JHF = 17.1, JHH = 7.5 Hz, 2H),
Notes and references
1.88–1.76 (m, 2H), 1.61 (t, JHF = 18.3 Hz, 3H), 1.60–1.48 (m, 2H),
1.45 (s, 9H). 13C NMR (100.6 MHz, CDCl3): δ = 210.37, 154.79,
123.72 (t, J = 238.0 Hz), 79.81, 48.89, 43.36 (br s), 33.36 (t, J =
3.7 Hz), 31.77 (t, J = 25.6 Hz), 28.57, 27.65, 23.99 (t, J = 27.8 Hz).
19F NMR (376 MHz, CDCl3): δ = −92.7 (m). HRMS (AJESI) calcd.
for C15H25F2NO3Na+ [M+Na]+ 328.1695, found m/z 328.1702.
6-(4-Bromophenyl)-5,5-difluoro-1-phenylhexan-2-one (6). Isolated
yield: 67% (124 mg). Column chromatography eluent –
petroleum ether/diethyl ether, 10:1. Colorless needles,
mp 88.0 °C (from diethyl ether/hexane). 1Н NMR (400 MHz,
CDCl3): δ = 7.46–7.41 (m, 2H), 7.36–7.30 (m, 2H), 7.29–7.25 (m,
1H), 7.21–7.16 (m, 2H), 7.08 (d, J = 8.1 Hz, 2H), 3.70 (s, 2H), 3.05
(t, JHF = 15.9 Hz, 2H), 2.66 (m, 2H), 2.11–1.96 (m, 2H). 13C NMR
(100.6 MHz, CDCl3): δ = 206.39, 133.95, 132.08, 132.07, 131.77,
129.49, 128.96, 127.33, 123.28 (t, J = 242.6 Hz), 121.75, 50.33,
43.07 (t, J = 26.2 Hz), 34.22 (t, J = 3.5 Hz), 29.95 (t, J = 25.0 Hz).
19F NMR (376 MHz, CDCl3): δ = −94.5 (quint, JHF = 16.7 Hz). HRMS
(AJESI) calcd. for C18H18BrF2O+ [M+H]+ 367.0504, found
m/z 367.0511.
‡ Crystal data for 6:
C18H17BrF2O, Mr = 367.22 g/mol, orthorhombic, Pnma (no. 62),
a = 34.5876(4) Å, b = 9.19962(10) Å, c = 4.92247(5) Å, V =
1566.29(3) Å3, Z = 4, T = 123.0 K, μ(Cu-Kα) = 3.762 mm−1, ρcalc
=
1.557 g/cm3, 13397 reflections measured (5.11° ≤ 2Θ ≤ 134.43°)
of which 1462 unique (Rint = 0.0195, Rsigma = 0.0074), final R1
[F2>2σ(F2)] = 0.0235, wR2 = 0.0627. The crystallographic data is
deposited with the Cambridge Crystallographic Data Centre
(CCDC 1536256) and can be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
1
For the recent reviews, see: a) C. Ni and J. Hu, Chem. Soc. Rev.,
2016, 45, 5441; b) C. Alonso, E. Martínez de Marigorta, G.
Rubiales and F. Palacios, Chem. Rev., 2015, 115, 1847; c) P.
Gao, X.-R. Song, X.-Y. Liu and Y.-M. Liang, Chem. Eur. J., 2015,
21, 7648; d) O. A. Tomashenko and V. V. Grushin, Chem. Rev.,
2011, 111, 4475; e) T. Koike and M. Akita, J. Fluor. Chem.,
2014, 167, 30; f) J. Charpentier, N. Früh and A. Togni, Chem.
Rev., 2015, 115, 650; g) S. Barata-Vallejo, S. Bonesi and A.
Postigo, Org. Biomol. Chem., 2016, 14, 7150; h) G. Landelle, A.
Panossian, S. Pazenok, J.-P. Vors and F. R. Leroux, Beilstein J.
Org. Chem., 2013, 9, 2476.
2
3
Y. Zeng, C. Ni and J. Hu, Chem. Eur. J., 2016, 22, 3210.
a) N. Yi, H. Zhang, C. Xu, W. Deng, R. Wang, D. Peng, Z. Zeng
and J. Xiang, Org. Lett., 2016, 18, 1780; b) Q. Luo, C. Liu, J.
Tong, Y. Shao, W. Shan, H. Wang, H. Zheng, J. Cheng and X.
Wan, J. Org. Chem., 2016, 81, 3103; c) B. Gao, Y. Zhao and J.
Hu, Angew. Chem. Int. Ed., 2015, 54, 638; d) M. M. Lerch, B.
Morandi, Z. K. Wickens and R. H. Grubbs, Angew. Chem. Int.
Ed., 2014, 53, 8654.
1-phenyl-4-(1-(trifluoromethyl)cyclopropyl)butan-2-one
(7).
Isolated yield: 23% (30 mg). Column chromatography eluent –
petroleum ether/diethyl ether, 10:1. 1Н NMR (400 MHz, CDCl3):
δ = 7.38–7.31 (m, 2H), 7.31–7.26 (m, 1H), 7.23–7.19 (m, 2H),
3.70 (s, 2H), 2.66 (m, 2H), 1.80 (m, 2H), 0.92 (m, 2H), 0.53 (m,
2H). 13C NMR (100.6 MHz, CDCl3): δ = 207.40, 134.09, 129.51,
128.90, 127.6 (q, J = 273.8 Hz), 127.25, 50.38, 39.48, 26.10,
21.97 (q, J = 32.3 Hz), 9.36 (q, J = 2.7 Hz). 19F NMR (376 MHz,
CDCl3): δ = −69.4 (s). HRMS (APCI) calcd. for C14H16F3O+ [M+H]+
257.1148, found m/z 257.1134.
5-Fluoro-1-phenylpentan-2-one (8a). Isolated yield: 13% (12 mg).
Column chromatography eluent – pentane/diethyl ether, 20:1.
1Н NMR (400 MHz, CDCl3): δ = 7.37–7.31 (m, 2H), 7.30–7.24 (m,
1H), 7.23–7.18 (m, 2H), 4.41 (dt, JHF = 47.3, JHH = 5.8 Hz, 2H), 3.71
(s, 2H), 2.61 (t, J = 7.1 Hz, 2H), 1.94 (dtt, JHF = 26.7, JHH = 7.1, 5.8
Hz, 1H). 13C NMR (100.6 MHz, CDCl3): δ = 207.47, 134.20,
129.51, 128.93, 127.25, 83.26 (d, J = 164.6 Hz), 50.40, 37.45 (d,
J = 4.4 Hz), 24.57 (d, J = 20.1 Hz). 19F NMR (376 MHz, CDCl3): δ =
4
5
a) X.-J. Tang, Z. Zhang and W. R. Dolbier, Chem. Eur. J., 2015,
21, 18961; b) L. Zhu, L.-S. Wang, B. Li, B. Fu, C.-P. Zhang and
W. Li, Chem. Comm., 2016, 52, 6371; c) R. Sakamoto, H.
Kashiwagi, S. Selvakumar, S. A. Moteki and K. Maruoka, Org.
Biomol. Chem., 2016, 14, 6417; d) T. Besset, D. Cahard and X.
Pannecoucke, J. Org. Chem., 2014, 79, 413; e) X. Mu, T. Wu,
H.-Y. Wang, Y.-l. Guo and G. Liu, J. Am. Chem. Soc., 2012, 134
,
878.
a) H. Egami, R. Shimizu, Y. Usui and M. Sodeoka, Chem.
Comm., 2013, 49, 7346; b) X. Liu, F. Xiong, X. Huang, L. Xu, P.
Li and X. Wu, Angew. Chem. Int. Ed., 2013, 52, 6962; c) Z.-M.
Chen, W. Bai, S.-H. Wang, B.-M. Yang, Y.-Q. Tu and F.-M.
Zhang, Angew. Chem. Int. Ed., 2013, 52, 9781; d) S. Martinez-
Erro, A. Sanz-Marco, A. Bermejo Gómez, A. Vázquez-Romero,
M. S. G. Ahlquist and B. Martín-Matute, J. Am. Chem. Soc.,
2016, 138, 13408; e) V. Bizet, X. Pannecoucke, J.-L. Renaud
and D. Cahard, J. Fluor. Chem., 2013, 152, 56.
−220.2 (tt, JHF = 47.4, 26.7 Hz). Spectral data correspond to those
9a,b
previously reported
tert-Butyl
.
6
a) F.-Q. Huang, Y.-W. Wang, J.-G. Sun, J. Xie, L.-W. Qi and B.
Zhang, RSC Advances, 2016,
6
, 52710; b) N. O. Ilchenko, M.
, 1056; c) T.-P.
4-(4-fluorobutanoyl)piperidine-1-carboxylate
(8b).
Hedberg and K. J. Szabo, Chem. Sci., 2017,
8
Isolated yield: 13% (18 mg). Column chromatography eluent –
petroleum ether/ethyl acetate, 5:1. 1Н NMR (400 MHz, CDCl3):
δ = 4.45 (dt, JHF = 47.3, JHH = 5.7 Hz, 2H), 4.11 (br s, 2H), 2.77 (br
t, J = 12.4 Hz, 2H), 2.62 (t, J = 7.1 Hz, 2H), 2.47 (tt, J = 18.2, 5.1
Hz, 1H), 1.97 (dtt, JHF = 27.0, JHH = 7.1, 5.7 Hz, 2H), 1.81 (m, 2H),
1.58–1.50 (m, 2H), 1.45 (s, 9H). 13C NMR (100.6 MHz, CDCl3): δ
= 211.33, 154.80, 83.29 (d, J = 164.5 Hz), 79.79, 48.87, 43.23,
36.00 (d, J = 4.1 Hz), 28.57, 27.63, 24.48 (d, J = 20.0 Hz). 19F NMR
Yang, Q. Li, J.-H. Lin and J.-C. Xiao, Chem. Comm., 2014, 50
1077.
,
7
8
J. K. Cha and O. G. Kulinkovich, Org. React., 2012, 77, 1.
a) A. Nikolaev and A. Orellana, Synthesis, 2016, 48, 1741; b) I.
Haym and M. A. Brimble, Org. Biomol. Chem., 2012, 10, 7649;
c) O. Kulinkovich, Eur. J. Org. Chem., 2004, 4517; d) O. G.
Kulinkovich, Chem. Rev., 2003, 103, 2597.
a) H. Zhao, X. Fan, J. Yu and C. Zhu, J. Am. Chem. Soc., 2015,
137, 3490; b) I. Naoki, O. Shintaro, N. Yuuta and M. Masahiro,
Chem. Lett., 2015, 44, 821; c) S. Bloom, D. D. Bume, C. R. Pitts
9
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins