D
N. Gandhamsetty et al.
Cluster
Synlett
Ph
N
SiPhMe2
SiPhMe2
N
X
1b
Ph
N
Ph
Ph
N
B(C6F5)3 (5 mol%)
CDCl3, 65 °C, 2 h
B(C6F5)3 (10 mol%)
(a)
+
+
PhMe2SiH
PhMe2SiH (2 equiv)
100 °C, 15 h
SiPhMe2
1b' (89%)a
2b'
2b''
(X = SiPhMe2 or H)
(1.1 equiv)
83%a (2b'/2b" = ca. 70:30)
SiPhMe2
H2 (1 atm)b
100 °C, 1 h
(b)
Ph
N
2b"
1b
+
+
50%a
2b'
50% combined yielda
(2b'/2b" = ca. 70:30)
Scheme 4 Preliminary mechanistic studies. Catalytic formation of the 1,4-product 1b′, followed by addition of B(C6F5)3 and PhMe2SiH (a) or H2 (1 atm)
(b). a The yield was determined by 1H NMR with 1,1,2,2-tetrachloroethane as the internal standard. b The crude solution of 1b′ was degassed by freeze–
pump–thaw cycling before H2 was introduced into the reactor.
tion.13 Similarly, exposing a solution of intermediate 1b′ to
an H2 atmosphere (1 atm) at 100 °C in the presence of
B(C6F5)3 (5 mol%) gave a mixture of 2b′ and 2b′′ in 50% com-
bined yield (2b′/2b′′ ≈ 70:30), together with ~50% of the
starting material 1b (Scheme 4, b). These results strongly
suggest that H2 generated in situ is the reductant involved
in the conversion of 1b′ into the tetrahydroquinoline prod-
ucts 2b′ and 2b′′, and that the conversion of 1b into 1b′ is
reversible, as evidenced by the formation of 1b upon heat-
ing a solution containing 1b′ at 100 °C for one hour.
In summary, we have developed the borane-catalyzed
reduction of substituted N-heteroaromatics with hydrosila-
nes, providing dearomatized azacyclic compounds. The use
of a hydrosilane as the reductant offers a convenient proce-
dure with a broad substrate scope that includes quinolines,
quinoxalines, and quinoline N-oxides within the B(C6F5)3
catalyst system. Moreover, amino- or hydroxy-substituted
quinolines were also reduced to the corresponding tetrahy-
droquinolines in one pot with good to excellent yields. Pre-
liminary mechanistic studies suggested a stepwise reduc-
tion sequence involving 1,4-hydrosilylation followed by re-
duction of the enamine intermediate with the H2 generated
in situ during the catalytic turnover.
References and Notes
(1) (a) Stout, D. M.; Meyers, A. I. Chem. Rev. 1982, 82, 223.
(b) Forrest, T. P.; Dauphinee, D. A.; Deraniyagala, S. A. Can. J.
Chem. 1985, 63, 412. (c) Keay, J. G. Adv. Heterocycl. Chem. 1986,
39, 1. (d) Keay, J. G. In Comprehensive Organic Synthesis;8Vo.
l
Trost, B.
M.; Fleming, I., Eds.; Pergamon: Oxford, 1991, 579. (e) Gribble,
G. W. Chem. Soc. Rev. 1998, 27, 395. (f) Pitts, M. R.; Harrison, J.
R.; Moody, C. J. J. Chem. Soc., Perkin Trans. 1 2001, 955.
(g) Hollmann, F.; Arends, I. W. C. E.; Buehler, K. ChemCatChem
2010, 2, 762. (h) Bull, J. A.; Mousseau, J. J.; Pelletier, G.; Charette,
A. B. Chem. Rev. 2012, 112, 2642. (i) Wan, J.-P.; Liu, Y. RSC Adv.
2012, 2, 9763. (j) Park, S.; Chang, S. Angew. Chem. Int. Ed. 2017,
in pressDOI: 10.1002/anie.201612140.
(2) (a) Krygowski, T. M.; Cryaňski, M. K. Chem. Rev. 2001, 101, 1385.
(b) Balaban, A. T.; Oniciu, D. C.; Katritzky, A. R. Chem. Rev. 2004,
104, 2777. (c) Pape, A. R.; Kaliappan, K. P.; Kündig, E. P. Chem.
Rev. 2000, 100, 2917.
(3) (a) Katritzky, A. R.; Rachwal, S.; Rachwal, B. Tetrahedron 1996,
52, 15031. (b) Sridharan, V.; Suryavanshi, P. A.; Menéndez, J. C.
Chem. Rev. 2010, 111, 7157.
(4) (a) Wu, J.; Wang, C.; Tang, W.; Pettman, A.; Xiao, J. Chem. Eur. J.
2012, 18, 9525. (b) Tang, W.-J.; Tan, J.; Xu, L.-J.; Lam, K.-H.; Fan,
Q.-H.; Chan, A. S. C. Adv. Synth. Catal. 2010, 352, 1055. (c) Wu, J.;
Tang, W.; Pettman, A.; Xiao, J. Adv. Synth. Catal. 2013, 355, 35.
(d) Ye, Z.-S.; Chen, M.-W.; Chen, Q.-A.; Shi, L.; Duan, Y.; Zhou, Y.-
G. Angew. Chem. Int. Ed. 2012, 51, 10181. (e) Dobereiner, G. E.;
Nova, A.; Schley, N. D.; Hazari, N.; Miller, S. J.; Eisenstein, O.;
Crabtree, R. H. J. Am. Chem. Soc. 2011, 133, 7547. (f) Adam, R.;
Cabrero-Antonino, J. R.; Spannenberg, A.; Junge, K.; Jackstell, R.;
Beller, M. Angew. Chem. Int. Ed. 2017, 56, 3216. (g) Chen, F.;
Surkus, A.-E.; He, L.; Pohl, M.-M. Radnik J., Topf C., Junge K., Beller
M. 2015, 137, 11718.
Funding Information
This research was supported by the Institute for Basic Science (IBS-
R010-D1) in Korea.
n
Itsu
i
te
o
f
r
Bacsi
Secince
K
ore
a
B
I(S-R
0
1
0-D1)
(5) (a) Hounjet, L. J.; Stephan, D. W. Org. Process Res. Dev. 2014, 18,
385. (b) Stephan, D. W.; Greenberg, S.; Graham, T. W.; Chase, P.;
Hastie, J. J.; Geier, S. J.; Farrell, J. M.; Brown, C. C.; Heiden, Z. M.;
Welch, G. C.; Ulrich, M. Inorg. Chem. 2011, 50, 12338.
(c) Paradies, J. Synlett 2013, 24, 777. (d) Erős, G.; Nagy, K.;
Mehdi, H.; Pápai, I.; Nagy, P.; Király, P.; Tárkányi, G.; Soós, T.
Chem. Eur. J. 2012, 18, 574. (e) Maier, A. F. G.; Tussing, S.;
Schneider, T.; Flörke, U.; Qu, Z.-W.; Grimme, S.; Paradies, J.
Supporting Information
Supporting information for this article is available online at
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E