C
M. A. Al-Saedy, J. P. Harrity
Letter
Synlett
(d) Gandon, V.; Leboeuf, D.; Amslinger, S.; Vollhardt, K. P. C.;
Malacria, M.; Aubert, C. Angew. Chem. Int. Ed. 2005, 44, 7114.
(e) Hilt, G.; Smolko, K. I. Angew. Chem. Int. Ed. 2003, 42, 2795.
(4) Kirkham, J. D.; Edeson, S. J.; Stokes, S.; Harrity, J. P. A. Org. Lett.
2012, 14, 5354.
PinB–Bdan
Bdan
Ph
Pd2(dba)3 (10 mol%)
Ph3As (20 mol%), Cs2CO3
Ph
DMA, 60 °C, 1 h
N
NHTs
Ts
12; 58%
(5) (a) Huang, J.; Macdonald, S. J. F.; Harrity, J. P. A. Chem. Commun.
2010, 46, 8770. (b) Warner, A. J.; Lawson, J. R.; Fasano, V.;
Ingleson, M. J. Angew. Chem. Int. Ed. 2015, 54, 11245. (c) Chong,
E.; Blum, S. A. J. Am. Chem. Soc. 2015, 137, 10144.
Scheme 5 Borylative cyclization using Suginome’s reagent
(6) For alternative approaches to 3-borylated indoles, see:
(a) Tasch, B. O. A.; Merkul, E.; Müller, T. J. J. Eur. J. Org. Chem.
2011, 4532. (b) Merkul, E.; Schäfer, E.; Müller, T. J. J. Org. Biomol.
Chem. 2011, 9, 3139. (c) Mkhalid, I. A. I.; Barnard, J. H.; Marder,
T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890.
(7) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873.
(8) Iwadate, N.; Suginome, M. J. Am. Chem. Soc. 2010, 132, 2548.
(9) Cid, J.; Carbó, J. J.; Fernández, E. Chem. Eur. J. 2014, 20, 3616.
(10) Amjad, M.; Knight, D. W. Tetrahedron Lett. 2004, 45, 539.
(11) Xu, L.; Li, P. Chem. Commun. 2015, 51, 5656.
(12) Kaila, N.; Follows, B.; Leung, L.; Thomason, J.; Huang, A.;
Moretto, A.; Janz, K.; Lowe, M.; Mansour, T. S.; Hubeau, C.; Page,
K.; Morgan, P.; Fish, S.; Xu, X.; Williams, C.; Saiah, E. J. Med.
Chem. 2014, 57, 1299.
(13) Representative Procedure for the Borylation of N-Tosyl 3-
Iodo Indoles – Synthesis of Indole 19
In conclusion, we have found that indole 3-pinacol bo-
ronic esters undergo facile protodeborylation in the pres-
ence of palladium catalysts and base, resulting in the gener-
ation of nonborylated indole byproducts. Suginome’s re-
agent provides an alternative method to access 3-borylated
indoles as these compounds are less susceptible to deboro-
nation. Efforts to extend the scope of this chemistry, in par-
ticular with respect to borylative cyclization and function-
alization of the C–B bond, are ongoing and will be reported
in due course.
Acknowledgment
We are grateful to The Iraqi Ministry of Higher Education and Scien-
tific Research and Al-Mustansiriyah University for financial support.
2-Cyclopropyl-3-iodo-1-tosyl-1H-indole (11, 200 mg, 0.455
mmol), Pd2(dba)3 (21 mg, 0.023 mmol), Cs2CO3 (297 mg, 0.910
mmol), PinB-Bdan (268 mg, 0.910 mmol) in MeOH (1 mL) was
stirred at reflux under a nitrogen atmosphere for 2 h. The reac-
tion mixture was allowed to cool to r.t., and EtOAc (10 mL) was
added. The organic extract was washed with H2O (2 × 5 mL) and
brine (5 mL), dried over MgSO4, and the solvents removed under
reduced pressure to provide the crude product. Purification of
the residue by flash chromatography on silica gel using a
solvent gradient of PE–EtOAc (95:5), increasing in polarity to
EtOAc gave the target compound 19 as a colorless solid (151 mg,
70%), mp 240–241 °C. 1H NMR (400 MHz, CDCl3): δ = 8.25 (d,
J = 8.5 Hz, 1 H), 7.77 (d, J = 8.5 Hz, 2 H), 7.57 (d, J = 7.5 Hz, 1 H,
ArH), 7.34–7.29 (m, 1 H, ArH), 7.25–7.20 (m, 3 H, ArH), 7.14 (dd,
J = 8.0, 7.5 Hz, 2 H), 7.07 (dd, J = 8.5, 1.0 Hz, 2 H), 6.35 (dd,
J = 7.0, 1.0 Hz, 2 H), 5.87 (s, 2 H), 2.39 (s, 3 H), 2.33 (tt, J = 8.5, 5.5
Hz, 1 H), 0.96 (dt, J = 8.5, 3.0 Hz, 2 H), 0.66–0.59 (m, 2 H). 13C
NMR (101 MHz, CDCl3): δ = 146.4, 144.6, 140.8, 137.6, 137.0,
136.3, 132.2, 129.7, 127.6, 126.6, 124.3, 123.3, 120.7, 119.8,
117.9, 114.5, 105.9, 21.6, 10.3, 8.9. 11B NMR (128 MHz, CDCl3):
Supporting Information
Supporting information for this article is available online at
S
u
p
p
ortioInfgrmoaitn
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ortiInfogrmoaitn
References and Notes
(1) Boronic Acids; Hall, D. G., Ed.; Wiley-VCH: Weinheim, 2005.
(2) For representative examples, see: (a) Bachollet, S. P. J. T.; Vivat, J.
F.; Cocker, D. C.; Adams, H.; Harrity, J. P. A. Chem. Eur. J. 2014, 20,
12889. (b) Crépin, D. F. P.; Harrity, J. P. A.; Jiang, J.; Meijer, A. J. H.
M.; Nassoy, A.-C. M. A.; Raubo, P. J. Am. Chem. Soc. 2014, 136,
8642. (c) Browne, D. L.; Taylor, J. B.; Plant, A.; Harrity, J. P. A.
J. Org. Chem. 2009, 74, 396. (d) Delaney, P. M.; Browne, D. L.;
Adams, H.; Plant, A.; Harrity, J. P. A. Tetrahedron 2008, 64, 866.
(3) (a) Stalling, T.; Harker, W. R. R.; Auvinet, A.-L.; Cornel, E. J.;
Harrity, J. P. A. Chem. Eur. J. 2015, 21, 2710. (b) Auvinet, A.-L.;
Harrity, J. P. A. Angew. Chem. Int. Ed. 2011, 50, 2769. (c) Auvinet,
A.-L.; Harrity, J. P. A.; Hilt, G. J. Org. Chem. 2010, 75, 3893.
δ = 30.9. FTIR: νmax = 3404, 3042, 2963, 2884, 1625, 1600 cm–1
HRMS (ESI-TOF): m/z [M
.
+
Na]+ calcd for C28H24BN3O2S:
500.1580; found: 500.1561.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–C