F
R. Piccardi et al.
Paper
Synthesis
13C NMR (CDCl3, 125 MHz): δ =138.0, 137.3, 129.8 (2 C), 129.0 (2 C),
128.4 (2 C), 128.3 (2 C), 127.9, 127.5, 92.6, 70.1, 62.6 (br), 60.3 (br), 8.7
(2 C), –0.1.
Supporting Information
Supporting information for this article is available online at
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HRMS (APCI): m/z [M + H]+ calcd for C19H20NO: 278.1539; found:
278.1532.
References
N-Benzyl-N-(7-chloro-1-phenylhept-2-yn-1-yl)hydroxylamine
(5d)
(1) (a) Wegner, J.; Ceylan, S.; Kirschning, A. Adv. Synth. Catal. 2012,
354, 17. (b) Baxendale, I. R. J. Chem. Technol. Biotechnol. 2013, 88,
519. (c) Basics of Flow Microreactor Synthesis, Springer Briefs in
Molecular Sciences Series; Yoshida, J., Ed.; Springer: Berlin, 2015.
(2) (a) Fukuyama, T.; Rahman, M. T.; Sato, M.; Ryu, R. Synlett 2008,
151. (b) Wegner, J.; Ceylan, S.; Kirschning, A. Chem. Commun.
2011, 47, 4583. (c) Wiles, C.; Watts, P. Green Chem. 2012, 14, 38.
(d) Wiles, C.; Watts, P. Micro Reaction Technology in Organic Syn-
thesis; Taylor and Francis: London, 2011, 1.
(3) (a) Ullah, F.; Zang, Q.; Javed, S.; Zhou, A.; Knudtson, C. A.; Bi, D.;
Hanson, P. R.; Organ, M. G. J. Flow Chem. 2012, 2, 118.
(b) Ranasinghe, N.; Jones, G. B. Curr. Green Chem. 2015, 2, 66.
(c) Manvar, A.; Shah, A. Asian J. Org. Chem. 2014, 11, 1134.
(d) Alcazar, J.; Munoz, J. M. In Microwaves in Organic Synthesis,
3rd ed., Vol. 2; De la Hoz, A.; Loupy, A., Eds.; Wiley-VCH: Wein-
heim, 2012, 1173.
(4) (a) Loubièrea, K.; Oelgemöllerc, M.; Aillet, T.; Dechy-Cabaret, O.;
Prat, L. Chem. Eng. Process. 2016, 104, 120. (b) Cambié, D.;
Bottecchia, C.; Straathof, N. J. W.; Hessel, V.; Noel, T. Chem. Rev.
2016, 116, in press; DOI: 10.1021/acs.chemrev.5b00707.
(c) Yuanhai, Su. Y.; Straathof, N. J. W.; Hessel, V.; Noel, T. Chem.
Eur. J. 2014, 20, 10562.
(5) (a) Price, G. A.; Bogdan, A. R.; Aguirre, A. L.; Iwai, T.; Djuricb, S.
W.; Organ, M. G. Catal. Sci. Technol. 2016, 6, in press; DOI:
10.1039/c6cy00331a. (b) Cantillo, D.; Kappe, C. O. Chem-
CatChem 2014, 6, 3286. (c) Hiroyuki, S.; Miyamura, H.;
Kobayashi, S. Acc. Chem. Res. 2014, 47, 1054. (d) Leadbeater, N. E.
In Comprehensive Organic Synthesis, 2nd ed., Vol. 9; Knochel, P.;
Molander, G. A., Eds.; Elsevier: Amsterdam, 2014, 234.
A solution of 2d in toluene (1.28 M, 520 μL, 0.67 mmol,1.28 equiv)
was added to a solution of (Z)-N-benzyl-1-phenylmethenimine oxide
(110 mg, 0.52 mmol, 1 equiv) in anhyd CH2Cl2 (1 mL), and the result-
ing mixture was stirred at r.t. for 1 h. The reaction was then cooled to
0 °C and quenched with a 2 M aq solution of Rochelle’s salt. The mix-
ture was stirred at r.t. for 1 h, then the two phases were separated.
The aqueous layer was extracted with EtOAc (2 ×), the combined or-
ganic layers were dried (MgSO4), filtered, and concentrated under re-
duced pressure. The crude residue was purified by silica gel column
chromatography using CH2Cl2/MeOH (40:1) as the eluent to obtain
compound 5d (138 mg, 0.42 mmol, 81%) as a white solid. Recrystalli-
zation from CH2Cl2/heptane (1:20) afforded pure 5d in 65% yield (112
mg, 0.34 mmol); mp 68–70 °C.
1H NMR (CDCl3, 500 MHz): δ = 7.44 (d, J = 7.4 Hz, 2 H), 7.35–7.15 (m, 8
H), 6.48 (br s, 1 H), 4.46 (s, 1 H), 3.82 (d, J = 12.6 Hz, 1 H), 3.58–3.55
(m, 3 H), 2.42 (td, J = 7.0, 2.0 Hz, 2 H), 2.00–1.90 (m, 2 H), 1.85–1.70
(m, 2 H).
13C NMR (CDCl3, 125 MHz): δ =137.7, 137.0, 129.9 (2 C), 129.1 (2 C),
128.4 (2 C), 128.2 (2 C) 128.0, 127.5, 88.2, 75.7, 62.3 (br), 60.0 (br),
44.6, 31.8, 26.1, 18.4.
HRMS (ESI): m/z [M + H]+ calcd for C20H23ClNO: 328.1463; found:
328.1461.
N-Benzyl-N-(1-phenylnona-2,8-diyn-1-yl)hydroxylamine (5e)
A solution of 2e in toluene (1.3 M, 520 μL, 0.68 mmol, 1.3 equiv) was
added to a solution of (Z)-N-benzyl-1-phenylmethenimine oxide (110
mg, 0.52 mmol, 1 equiv) in anhyd CH2Cl2 (1 mL), and the resulting
mixture was stirred at r.t. for 1 h. The reaction was then cooled to 0 °C
and quenched with a 2 M aq solution of Rochelle’s salt. The mixture
was stirred at r.t. for 1 h, then the two phases were separated. The
aqueous layer was extracted with EtOAc (2 ×), the combined organic
layers were dried (MgSO4), filtered, and concentrated under reduced
pressure. The crude residue was purified by silica gel column chroma-
tography using CH2Cl2/MeOH (40:1) as the eluent to afford compound
5e (85 mg, 0.27 mmol, 51%) as a white amorphous solid.
(6) (a) Finelli, F. G.; Mirandab, L. S. M.; de Souza, R. O. M. A. Chem.
Commun. 2015, 51, 3708. (b) Tsubogo, T.; Ishiwata, T.;
Kobayashi, S. Angew. Chem. Int. Ed. 2013, 52, 6590.
(7) (a) Pastre, J. C.; Browne, D. L.; Ley, S. V. Chem. Soc. Rev. 2013, 42,
8849. (b) Baumann, M.; Baxendale, I. R. Beilstein J. Org. Chem.
2015, 11, 1194. (c) Baumann, M.; Baxendale, I. R.; Ley, S. V. Mol.
Divers. 2011, 15, 613. (d) Porta, R.; Benaglia, M.; Puglisi, A. Org.
Process Res. Dev. 2016, 20, 2.
(8) For some recent examples, see: (a) Becker, M. R.; Ganiek, M. A.;
Knochel, P. Chem. Sci. 2015, 6, 6649. (b) Petersen, T. P.; Becker,
M. R.; Knochel, P. Angew. Chem. Int. Ed. 2014, 53, 7933.
(c) Nagaki, A.; Ichinari, D.; Yoshida, J. J. Am. Chem. Soc. 2014,
136, 12245. (d) Wakami, H.; Yoshida, J. Org. Process Res. Dev.
2005, 9, 787. (e) Kupracza, L.; Kirschning, A. Adv. Synth. Catal.
2013, 355, 3375. (f) Browne, D. L.; Harji, B. H.; Ley, S. V. Chem.
Eng. Technol. 2013, 36, 959. (g) Newby, J. A.; Huck, L.; Blaylock,
D. W.; Witt, P. M.; Ley, S. V.; Browne, D. L. Chem. Eur. J. 2014, 20,
263. (h) Fukuyama, T.; Totoki, T.; Ryu, I. Org. Lett. 2014, 16,
5632. (i) Pieber, B.; Glasnov, T.; Kappe, C. O. RSC Adv. 2014, 4,
13430. (j) Becker, M. R.; Knochel, P. Angew. Chem. Int. Ed. 2015,
54, 12501. (k) Ganiek, M. A.; Becker, M. R.; Ketels, M.; Knochel,
P. Org. Lett. 2016, 18, 828. (l) Becker, M. R.; Knochel, P. Org. Lett.
2016, 18, 1462. (m) Brodmann, T.; Koos, P.; Metzger, A.;
Knochel, P.; Ley, S. V. Org. Process Res. Dev. 2012, 16, 1102.
(n) Yoshida, J.; Takahashi, Y.; Nagaki, A. Chem. Commun. 2013,
49, 9896. (o) Nagaki, A.; Uesugi, Y.; Kim, H.; Yoshida, J. Chem.
1H NMR (CDCl3, 500 MHz): δ = 7.41 (d, J = 7.4 Hz, 2 H), 7.28–7.13 (m, 8
H), 5.94 (br, 1 H), 4.47 (s, 1 H), 3.77 (d, J = 12.6 Hz, 1 H), 3.61 (d, J =
12.6 Hz, 1 H), 2.40–2.24 (m, 2 H), 2.23–2.11 (m, 2 H), 1.87 (t, J = 2.7
Hz, 1 H), 1.74–1.56 (m, 4 H).
13C NMR (CDCl3, 125 MHz): δ = 137.9, 137.3, 129.8 (2 C), 129.0 (2 C),
128.4 (2 C), 128.3 (2 C), 128.0, 127.5, 88.7, 84.2, 75.4, 68.7, 62.6 (br),
60.3 (br), 27.9, 27.8, 18.6, 18.1.
HRMS (ESI): m/z [M + H]+ calcd for C22H24NO: 318.1852; found:
318.1857.
Acknowledgment
We gratefully thank the CNRS, University Paris Descartes, and the
Agence Nationale de la Recherche (ANR, Tribal project) for financial
support.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G