E
I. Sasaki et al.
Letter
Synlett
(2) For applications of borylated heteroarenes in syntheses of
natural products, see: (a) Zhou, S.; Jia, Y. Org. Lett. 2014, 16,
3416. (b) Han, S.; Morrison, K. C.; Hergenrother, P. J.;
Movassaghi, M. J. Org. Chem. 2013, 79, 473. (c) McMurray, L.;
O’Hara, F.; Gaunt, M. J. Chem. Soc. Rev. 2011, 40, 1885. (d) Han,
S.; Movassaghi, M. J. Am. Chem. Soc. 2011, 133, 10768.
(e) Gutekunst, W. R.; Baran, P. S. Chem. Soc. Rev. 2011, 40, 1976.
(f) Beck, E. M.; Hatley, R.; Gaunt, M. J. Angew. Chem. Int. Ed.
2008, 47, 3004.
(9) For an example of carbonyl-directed borylation of heteroaro-
matic compounds with a silica-supported iridium catalyst, see:
Kawamorita, S.; Ohmiya, H.; Sawamura, M. J. Org. Chem. 2010,
75, 3855.
(10) For examples of ortho borylations of functionalized arenes
reported by other groups, see: (a) Ros, A.; Fernández, R.;
Lassaletta, J. M. Chem. Soc. Rev. 2014, 43, 3229. (b) Xiao, B.; Li, Y.-
M.; Liu, Z.-J.; Yang, H.-Y.; Fu, Y. Chem. Commun. 2012, 48, 4854.
(c) Dai, H.-X.; Yu, J.-Q. J. Am. Chem. Soc. 2012, 134, 134. (d) Hurst,
T. E.; Macklin, T. K.; Becker, M.; Hartmann, E.; Kügel, W.; Salle, P.
L.; Batsanov, A. S.; Marder, T. B.; Snieckus, V. Chem. Eur. J. 2010,
16, 8155. (e) Yamazaki, K.; Kawamorita, S.; Ohmiya, H.;
Sawamura, M. Org. Lett. 2010, 12, 3978. (f) Kawamorita, S.;
Ohmiya, H.; Hara, K.; Fukuoka, A.; Sawamura, M. J. Am. Chem.
Soc. 2009, 131, 5058.
(11) For bioactive heteroaromatic compounds bearing a formyl or
imino group, see: (a) Clemens, L.; Quaranta, L.; Edmunds, A.;
Pouliot, M.; Trah, S. WO 2012069601, 2012. (b) Shoujun, C.;
Junyi, Z.; Jun, J.; Gary, B.; Nha, V.; Qinglin, C.; Zhiqiang, X.; Lijun,
S. WO 2010039237, 2010. (c) Yu, X.; Park, E.-J.; Kondratyuk, T.
P.; Pezzuto, J. M.; Sun, D. Org. Biomol. Chem. 2012, 10, 8835.
(12) Sasaki, I.; Amou, T.; Ito, H.; Ishiyama, T. Org. Biomol. Chem. 2014,
12, 2041.
(3) For C–H borylation of heteroarenes with transition-metal cata-
lysts, see: (a) Dombray, T.; Werncke, C. G.; Jiang, S.; Grellier, M.;
Vendier, L.; Bontemps, S. B.; Sortais, J.-B.; Sabo-Etienne, S.;
Darcel, C. J. Am. Chem. Soc. 2015, 137, 4062. (b) Maegawa, Y.;
Inagaki, S. Dalton Trans. 2015, 44, 13007. (c) Furukawa, T.;
Tobisu, M.; Chatani, N. Chem. Commun. 2015, 51, 6508.
(d) Larsen, M. A.; Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 4287.
(e) Green, A. G.; Liu, P.; Merlic, C. A.; Houk, K. J. Am. Chem. Soc.
2014, 136, 4575. (f) Sadler, S. A.; Tajuddin, H.; Mkhalid, I. A.;
Batsanov, A. S.; Albesa-Jove, D.; Cheung, M. S.; Maxwell, A. C.;
Shukla, L.; Roberts, B.; Blakemore, D. C.; Lin, Z.; Marder, T. B.;
Steel, P. G. Org. Biomol. Chem. 2014, 12, 7318. (g) Konishi, S.;
Kawamorita, S.; Iwai, T.; Steel, P. G.; Marder, T. B.; Sawamura, M.
Chem. Asian J. 2014, 9, 434. (h) Preshlock, S. M.; Plattner, D. L.;
Maligres, P. E.; Krska, S. W.; Maleczka, R. E. Jr.; Smith, M. R. III.
Angew. Chem. Int. Ed. 2013, 52, 12915. (i) Tajuddin, H.;
Harrisson, P.; Bitterlich, B.; Collings, J. C.; Sim, N.; Batsanov, A.
S.; Cheung, M. S.; Kawamorita, S.; Maxwell, A. C.; Shukla, L.;
Morris, J.; Lin, Z.; Mader, T. B.; Steel, P. G. Chem. Sci. 2012, 3,
3505. (j) Mkhalid, I. A.; Barnard, J. H.; Marder, T. B.; Murphy, J.
M.; Hartwig, J. F. Chem. Rev. 2009, 110, 890. (k) Kallepalli, V. A.;
Shi, F.; Paul, S.; Onyeozili, E. N.; Maleczka, R. E. Jr.; Smith, M. R.
III. J. Org. Chem. 2009, 74, 9199. (l) Mkhalid, I. A. I.; Coventry, D.
N.; Albesa-Jove, D.; Batsanov, A. S.; Howard, J. A. K.; Perutz, R.
N.; Marder, T. B. Angew. Chem. Int. Ed. 2006, 45, 489.
(13) Borylation of Heteroaromatic Aldimine 1a; General Proce-
dure
An oven-dried two-necked flask was charged with
[Ir(OMe)(cod)]2 (5.0 mg, 7.5 μmol), borane 2 (152.4 mg, 0.60
mmol), and 1,10-phen (2.7 mg, 15 μmol). The flask was con-
nected to a vacuum/N2 manifold through a rubber tube, evacu-
ated, and backfilled with N2. This cycle was repeated three
times. Mesitylene (3.0 mL) was then added in the flask through
a rubber septum by using a syringe and the mixture was stirred
at r.t. for 15 min. Next, 1 (0.50 mmol) was added from a syringe
and the mixture was stirred at r.t. When the reaction was com-
plete, the mixture was initially purified by Kugelrohr distilla-
tion. The resulting mixture was crystallized from hexane. See
the Supporting Information for characterization data of all com-
pounds 3. Data for 3a are given here as an example.
(4) Ishiyama, T.; Takagi, J.; Yonekawa, Y.; Hartwig, J. F.; Miyaura, N.
Adv. Synth. Catal. 2003, 345, 1103.
(5) For regioselective C–H borylations of arenes at the meta posi-
tion by using bidentate ligands, see: (a) Hartwig, J. F. Chem.
Soc. Rev. 2011, 40, 1992. (b) Murphy, J. M.; Liao, X.; Hartwig,
J. F. J. Am. Chem. Soc. 2007, 129, 15434. (c) Tzschucke, C. C.;
Murphy, J. M.; Hartwig, J. F. Org. Lett. 2007, 9, 761. (d) Paul, S.;
Chotana, G. A.; Holmes, D.; Reichle, R. C.; Maleczka, R. E. Jr.;
Smith, M. R. III. J. Am. Chem. Soc. 2006, 128, 15552. (e) Ishiyama,
T.; Miyaura, N. Pure Appl. Chem. 2006, 78, 1369. (f) Ishiyama, T.;
Nobuta, Y.; Hartwig, J. F.; Miyaura, N. Chem. Commun. 2003,
2924. (g) Ishiyama, T.; Miyaura, N. J. Organomet. Chem. 2003,
680, 3. (h) Takagi, J.; Sato, K.; Hartwig, J. F.; Ishiyama, T.;
Miyaura, N. Tetrahedron Lett. 2002, 43, 5649.
(6) Chotana, G. A.; Rak, M. A.; Smith, M. R. III. J. Am. Chem. Soc. 2005,
127, 10539.
(7) Sasaki, I.; Taguchi, J.; Hiraki, S.; Ito, H.; Ishiyama, T. Chem. Eur. J.
2015, 21, 9236.
(8) Our group has reported ortho borylations of functionalized
arenes, see: (a) Itoh, H.; Kikuchi, T.; Ishiyama, T.; Miyaura, N.
Chem. Lett. 2011, 40, 1007. (b) Ishiyama, T.; Isou, H.; Kikuchi, T.;
Miyaura, N. Chem. Commun. 2010, 46, 159.
The NMR yield of 3a in the crude mixture was 79%. The reaction
mixture was first purified by Kugelrohr distillation (34 Pa, 180
°C). Then, the resulting mixture was recrystallized from hexane
to obtain 3a (76.2 mg, 0.19 mmol, 38%) as a white solid from 1a
1
(137.6 mg, 0.50 mmol); mp 149 °C. H NMR (396 MHz, CDCl3):
δ = 1.32 (s, 12 H), 2.45 (d, J = 1.2 Hz, 3 H), 6.40 (s, 1 H), 8.69 (s, 1
H). 13C NMR (99 MHz, CDCl3): δ = 13.7 (CH3), 24.7 (CH3), 84.2
(C), 113.5 (CH), 127.0 (dt, J = 4.2, 12.4 Hz, C), 136.4–136.8 (m,
CF), 139.0–139.3 (m, CF), 141.5–141.6 (m, CF), 155.7 (C), 156.2
(CH), 158.1 (C). The carbon directly attached to the boron atom
was not detected, likely due to quadrupolar relaxation. 19F NMR
(373 MHz, CDCl3): δ = –153.6 (d, J = 14.2 Hz, 2 F), –161.5 (t, J =
21.6 Hz, 1 F), –163.9 (t, J = 17.9 Hz, 2 F). HRMS-EI (m/z): [M]+
calcd for C18H1710BF5NO3, 400.12580; found, 400.12638.
(14) (a) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.;
Miyaura, N.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 14263.
(b) Tamura, H.; Yamazaki, H.; Sato, H.; Sakaki, S. J. Am. Chem.
Soc. 2003, 125, 16114.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E