Catalytic metal-free Si-N cross-dehydrocoupling

Article abstract of DOI:10.1039/c3cc49558b

The metal-free B(C₆F₅)₃ catalyzed dehydrocoupling of hydrosilanes with anilines, carbazoles and indoles is reported. For anilines and carbazoles the reaction proceeds by the liberation of H₂ as the sole Si-N cou

Full text of DOI:10.1039/c3cc49558b

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Catalytic metal-free Si–N cross-dehydrocoupling†
Lutz Greb,‡ Sergej Tamke‡ and Jan Paradies*
Cite this: Chem. Commun., 2014,
50, 2318
Received 17th December 2013,
Accepted 10th January 2014
DOI: 10.1039/c3cc49558b
www.rsc.org/chemcomm
The metal-free B(C6F5)3 catalyzed dehydrocoupling of hydrosilanes
with anilines, carbazoles and indoles is reported. For anilines and
carbazoles the reaction proceeds by the liberation of H2 as the
sole Si–N coupling byproduct. Indoles react with diphenyl(methyl)
hydrosilane to give N-silyl indolines with high diastereoselectivity
(d.r. 10 : 1) in excellent yields. A mechanism for this Si–N coupling/
hydrogenation sequence is proposed.
The cross-dehydrocoupling is an efficient methodology for the con-
nection of two molecular entities.1 Especially the dehydrocoupling of
Si–H and N–H fragments provides an environmentally benign access
to silyl-protected amines.2 These ubiquitous structural motifs are
Scheme 1 Conceptional outline for the Si–N dehydrocoupling.
Indeed, when bis(4-toloyl)amine (5a) was reacted with diphenyl-
usually obtained by the reaction of halosilanes with deprotonated (methyl) silane (4a) in the presence of 5 mol% B(C6F5)3 (2) at room
amines, the generation of which often requires strong bases.3 This is temperature, the silylamine 6a was obtained in 95% yield accom-
not only of concern for atom efficiency but also for functional group panied with the evolution of H2 (Table 1, entry 1). In the absence of
tolerance. In light of this, the Si–N dehydrocoupling proved very the catalyst, the formation of 6a was not observed even when a
useful, e.g. for the protection of indoles using Zn(OTf)2 (10 mol%) in mixture of 5a and 4a was heated to 90 1C for 12 h (Table 1, entry 2).
the presence of 0.5–1.0 equiv. of pyridine.4 Oestreich’s sulfur-bridged The catalyst loading was reduced to 1 mol% with slight erosion in
Ru–arene complex5 is particularly effective in the base-free dehydro- yield (73%, entry 3). Lower catalyst loadings of 0.1 mol% led to
coupling of silanes with other nitrogen-containing heterocycles, e.g. significantly reduced yields (entry 4). Further experiments were
indole, carbazole and pyrrole derivatives using only 1 mol% of catalyst carried out with 1 mol% of 2 as catalyst.
loading.6 However, a metal-free variant has not yet been disclosed.7
The reaction displays a remarkable substrate scope. Besides
We have shown earlier that the H2-activation product 1 of the diphenylamine derivatives (5a and 5b, entries 3 and 5), carbazole
frustrated Lewis pair (FLP) consisting of 2/3 is a transient species derivatives 5c-f also proved to be viable substrates and the products
which readily releases H2 at room temperature (Scheme 1, top).8 6c-f were obtained in 83–97% yields (entries 6–9). The bibromo
Accordingly, the isostructural intermediate iso-1, generated through derivative required 70 1C to undergo Si–N cross-dehydrocoupling in
the silyl-transfer from the silane 4 to the aniline 5a, should readily 51% yield without the observation of dehalogenation (entry 8). The
liberate H2 with concomitant release of the Si–N coupling product 6 reduced yield was attributed to the very low solubility of 5e in toluene.
(Scheme 1, bottom). As a potential silyl-transfer catalyst, borane 2 has Other silanes were also useful in the Si–N coupling reaction. Triethyl-
attracted significant attention in hydrosilylation of aldehydes, ketones, silane (4b) or 1,1,3,3-tetramethyldisiloxane (4c) readily reacted with
imines and olefins.9 An analogous mechanism was only recently carbazole (5c) or bis(4-tolyl)amine (5a) in high yields (entries 9 and 10).
proposed by Oestreich as a competing pathway in the borane- The silylation of primary aniline derivatives proceeded at 60–70 1C in
promoted imine reduction with hydrosilanes.9a
excellent yields (88–97%, entries 11–15).10 The electron-deficient
anilines 5m and 5n were reactive even at room temperature and
6m and 6n were obtained in 88% and 97% yields (entries 16 and 17).
Also the two diamines N,N0-(diphenyl)-1,4-phenylene diamine (5o)
and N,N0-(diphenyl)-ethylene diamine (5p) underwent silylation with
diphenylmethyl silane (4a) in high yields (entries 18 and 19).
Institute for Organic Chemistry, Karlsruhe Institute of Technology (KIT),
Fritz-Haber-Weg 6, D-76131 Karlsruhe, Germany. E-mail: jan.paradies@kit.edu
† Electronic supplementary information (ESI) available: Experimental proce-
dures, analytical data. See DOI: 10.1039/c3cc49558b
‡ Both authors contributed evenly.
2318 | Chem. Commun., 2014, 50, 2318--2320
This journal is ©The Royal Society of Chemistry 2014

View Article Online
Communication
ChemComm
Table 1 Si–N cross-dehydrocoupling of aromatic amines with hydrosilanesa
Table 1 (continued)
Entry t [h] T [1C] Product
Yield [%]
Entry t [h] T [1C] Product
Yield [%]
92
1
2
3
4
1
25
12 90
25
10 25
95b
Diarylamines
0c
25
24 70
1
73
32d
a
b
Reactions were performed on a 1.0 mmol scale, 3 M in CH2Cl2.
5
6
1
1
25
25
91
97
c
d
e
5 mol% 2. Absence of 2. 0.1 mol% B(C6F5)3. 10 mol% 2, 0.1 mmol
scale, 3 M in CD2Cl2, yield determined by 1H NMR. 2 mol% 2.
f
Accordingly, the reaction of 5p with phenylsilane (4d) provided
the cyclic product 6q in 83% yield (entry 20).
7
8
1
25
83
Finally, we investigated the potential of the Si–N dehydro-
coupling for pyrrole and indole derivatives. While pyrrole-
derivatives were unreactive under our reaction conditions,11 the
indole-derivatives 5r–v displayed high reactivity. The indoles 5r–v were
chemospecifically converted into the 1-silylated indoline derivatives
6r–v (entries 21–25) without the formation of unsaturated side
products arising from N or C3-silylation.12 Indole (5r) required
prolonged reaction time (144 h, entry 21) for the domino silylation/
reduction sequence and indoline (6r) was obtained in 50% yield. The
less electron-rich 6-chloroindole (5s) was transformed into 6s in
excellent yield in only 24 h (95%, entry 22). Substituents in position
2 were well tolerated and the 2-methyl and 2-phenyl indolines 5t and
5u were obtained in quantitative yields (96% and 97%, entries 3–5).
2,3-dimethylindole (5v) was diastereoselectively reduced to cis-2,3-
dimethyl indoline (6v) in quantitative yield (98%, d.r. 10 : 1).13
The high chemospecificity and diastereoselectivity prompted us to
investigate the Si–N cross coupling/hydrogenation reaction of 5v with
4a in detail (Scheme 2). Only resonances of the starting materials and
the product 6v were observed when the reaction was monitored by
1H NMR (1 mol% 3, [D8]-toluene). Neither the resonance of FLP-
activated H2 nor the resonance of dissolved H2 was observed by
1H NMR. Deuterium labeling experiments were conducted to inves-
tigate the fate of the hydridic and protic hydrogen atoms in silane 4a
24 25
95e
9
1
1
25
25
95e
97
10
11
12
72 70
48 70
90b
90
Anilines
13
14
15
48 70
36 60
24 60
93
97
91
16
17
36 25
24 25
88
97
18
24 25
26 f
Diamines
19
20
24 70
24 60
92b
83
21
144 70
50e
Indoles
22
23
24
24 70
24 70
24 70
81
96
97
Scheme 2 Isotope labelling experiments with (a) 1-D-2,3-dimethylindole
(1-(D)-4v), with (b) D-SiMePh2 (D-4a) and (c) cross experiment.
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 2318--2320 | 2319

View Article Online
ChemComm
Communication
2 For reviews, see: (a) R. Waterman, Chem. Soc. Rev., 2013, 42, 5629;
(b) E. M. Leitao, T. Jurca and I. Manners, Nat. Chem., 2013, 5, 817;
(c) M. S. Hill, D. J. Liptrot, D. J. MacDougall, M. F. Mahon and
T. P. Robinson, Chem. Sci., 2013, 4, 4212; (d) J. Y. Corey, Chem. Rev.,
2011, 111, 863; (e) J. F. Harrod, Coord. Chem. Rev., 2000, 206, 493;
( f ) J. A. Reichl and D. H. Berry, Adv. Organomet. Chem., 1998, 43, 197;
for pioneering work, see: (g) E. Matarasso-Tchiroukhine, Chem.
Commun., 1990, 681; for recent examples, see: (h) J. F. Dunne,
S. R. Neal, J. Engelkemier, A. Ellern and A. D. Sadow, J. Am. Chem.
Soc., 2011, 133, 16782; (i) C. K. Toh, H. T. Poh, C. S. Lim and
W. Y. Fan, J. Organomet. Chem., 2012, 717, 9; ( j) F. Buch and
S. Harder, Organometallics, 2007, 26, 5132; (k) A. Iida, A. Horii,
T. Misaki and Y. Tanabe, Synthesis, 2005, 2677; (l) F. Lunzer,
C. Marschner and S. Landgraf, J. Organomet. Chem., 1998, 568, 253;
(m) H. Q. Liu and J. F. Harrod, Can. J. Chem., 1992, 70, 107;
(n) H. Q. Liu and J. F. Harrod, Organometallics, 1992, 11, 822;
(o) W. D. Wang and R. Eisenberg, Organometallics, 1991, 10, 2222;
(p) Y. D. Blum, K. B. Schwartz and R. M. Laine, J. Mater. Sci., 1989,
24, 1707; (q) Y. Blum and R. M. Laine, Organometallics, 1986, 5, 2081.
3 (a) P. G. M. Wuts and T. W. Greene, Protective Group in
Organic Chemistry, John Wiley & Sons, Inc., Hoboken, New Jersey,
4th edn, 2007; (b) S. Djuric, J. Venit and P. Magnus, Tetrahedron
Lett., 1981, 22, 1787.
Scheme 3 Proposed catalytic cycle for the Si–N coupling/hydrogenation
domino reaction.
and indole 5v. The reaction of 1-D-2,3-dimethyl indole (1-D-5v, 95% D)
with H–SiMePh2 (4a) gave exclusively cis-3-D-2,3-dimethyl indoline
(3-D-6v) in high yields (97%, 92% D-incorporation, Scheme 2a).
The reaction of D–SiMePh2 (D-2a, 95% D) with 5v provided
exclusively cis-2-D-2,3-dimethyl indoline (2-D-6v) in 96% yield
with 92% D-incorporation at position 2. Together the chemo-
selective deuteration and the absence of dissolved or FLP-
activated H2 or HD14 strongly support a N-silylation/rearrangement/
reduction mechanism (Scheme 3). The product of the B(C6F5)3-
catalyzed silyl-transfer to 5v is 1-silyl-1-H-indol-1-ium 6, which
rearranges to the more stable 1-silyl-3-H-indol-1-ium 7. Alternatively,
an intermolecular proton-transfer might be conceivable. However,
according to our cross experiment using 5t–u and 1-silyl-indole
8, the sigmatropic rearrangement mechanism is more likely
(Scheme 2c). The indole derivatives 5t and 5u were equally
reactive as 5v (96–98%, 24 h, see Table 1, entries 23–25) and
should be readily protonated by transiently formed 6 (formed
by the reaction of 5 and 4a, compare Scheme 3). However, the
reaction of an equimolar mixture of 8, 5t–u, and 4a in the
presence of 10 mol% 2 produced 6t or 6u as the product (6u/6v
>95 : 5; 6t : 6v >90 : 10). This is a strong indication that inter-
molecular proton-transfer is not operative in the silylation/
hydrogenation reaction sequence. The final step in the catalytic
cycle is the hydride transfer from [H–B(C6F5)3] to the highly
electrophilic iminium species 7 from the least hindered side
liberating cis-6v and the catalyst 2.
4 T. Tsuchimoto, Y. Iketani and M. Sekine, Chem.–Eur. J., 2012,
18, 9500.
5 (a) T. Stahl, H. F. T. Klare and M. Oestreich, J. Am. Chem. Soc., 2013,
135, 1248; (b) T. Stahl, K. Muether, Y. Ohki, K. Tatsumi and
M. Oestreich, J. Am. Chem. Soc., 2013, 135, 10978; (c) C. D. F. Konigs,
H. F. T. Klare, Y. Ohki, K. Tatsumi and M. Oestreich, Org. Lett., 2012,
14, 2842; (d) H. F. T. Klare, M. Oestreich, J.-i. Ito, H. Nishiyama, Y. Ohki
and K. Tatsumi, J. Am. Chem. Soc., 2011, 133, 3312; (e) Y. Ohki,
Y. Takikawa, H. Sadohara, C. Kesenheimer, B. Engendahl, E. Kapatina
and K. Tatsumi, Chem.–Asian J., 2008, 3, 1625.
6 C. D. F. Koenigs, M. F. Mueller, N. Aiguabella, H. F. T. Klare and
M. Oestreich, Chem. Commun., 2013, 49, 1506.
7 For metal-free silylation of OH-groups, see: (a) D. J. Gao and
C. M. Cui, Chem.–Eur. J., 2013, 19, 11143; (b) for metal-free silylation
of P–P bonds, see: S. J. Geier and D. W. Stephan, Chem. Commun.,
2010, 46, 1026.
˜
8 (a) L. Greb, S. Tussing, B. Schirmer, P. Ona-Burgos, K. Kaupmees,
M. Lokov, I. Leito, S. Grimme and J. Paradies, Chem. Sci., 2013,
˜
4, 2788; (b) L. Greb, P. Ona-Burgos, B. Schirmer, S. Grimme,
D. W. Stephan and J. Paradies, Angew. Chem., Int. Ed., 2012, 51, 10164.
9 (a) J. Hermeke, M. Mewald and M. Oestreich, J. Am. Chem. Soc.,
˜
2013, 46, 17537; (b) L. Greb, P. Ona-Burgos, A. Kubas, F. C. Falk,
F. Breher, K. Fink and J. Paradies, Dalton Trans., 2012, 40, 9056;
(c) W. E. Piers, A. J. V. Marwitz and L. G. Mercier, Inorg. Chem., 2011,
50, 12252; (d) A. Berkefeld, W. E. Piers and M. Parvez, J. Am. Chem.
Soc., 2010, 132, 10660; (e) J. M. Blackwell, D. J. Morrison and
W. E. Piers, Tetrahedron, 2002, 58, 8247; ( f ) M. Rubin, T. Schwier
and V. Gevorgyan, J. Org. Chem., 2002, 67, 1936; (g) D. J. Parks,
J. M. Blackwell and W. E. Piers, J. Org. Chem., 2000, 65, 3090;
(h) J. M. Blackwell, E. R. Sonmor, T. Scoccitti and W. E. Piers, Org.
Lett., 2000, 2, 3921; (i) W. E. Piers and T. Chivers, Chem. Soc. Rev.,
1997, 26, 345; ( j) D. J. Parks and W. E. Piers, J. Am. Chem. Soc., 1996,
118, 9440.
In summary, we have developed the metal-free Si–N cross-
dehydrocoupling for primary and secondary aryl amines having
solely molecular hydrogen as byproduct. Indole derivatives
undergo N-silylation followed by a rearrangement/reduction
sequence to furnish indolines in high yields and high diastereo-
selectivity (d.r. 10: 1).
10 The elevated temperature of 60–70 1C was required to thermally
cleave the aniline/B(C6F5)3 adduct as evidenced by 11B NMR.
11 Neither N- nor C3-silylation products were observed, see:
L. D. Curless, E. R. Clark, J. J. Dunsford and M. J. Ingleson, Chem.
Commun., 2014, DOI: 10.1039/c3cc47372d.
12 For B(C6F5)3-catalyzed 1,4-hydrosilylation of 2-phenyl chinoline, see:
S. J. Geier, P. A. Chase and D. W. Stephan, Chem. Commun., 2010,
46, 4884.
13 Determined by deprotection of 6v and comparison of the 1H NMR
spectra of the resulting 1-H indoline with literature reported NMR
data: F. O. Arp and G. C. Fu, J. Am. Chem. Soc., 2006, 128, 14264.
Notes and references
1 For reviews, see: (a) C. S. Yeung and V. M. Dong, Chem. Rev., 2011, 14 Although the hydrogenation of N-methyl indoles is reported
111, 1215; (b) C. J. Scheuermann, Chem.–Asian J., 2010, 5, 436;
(c) G. E. Dobereiner and R. H. Crabtree, Chem. Rev., 2010, 681;
(d) C. J. Li, Acc. Chem. Res., 2009, 42, 335; for recent examples, see:
(e) X. M. Jie, Y. P. Shang, P. Hu and W. P. Su, Angew. Chem., Int. Ed.,
2013, 52, 3630; ( f ) N. Kuhl, M. N. Hopkinson and F. Glorius, Angew.
Chem., Int. Ed., 2012, 51, 8230.
(10 mol% 2, 103 bar H2, 80 1C, see: D. W. Stephan, S. Greenberg,
T. W. Graham, P. Chase, J. J. Hastie, S. J. Geier, J. M. Farrell,
C. C. Brown, Z. M. Heiden, G. C. Welch and M. Ullrich, Inorg.
Chem., 2011, 50, 12338) the hydrogenation of 1-silyl-2,3-dimethyl
indole (4 bar H2) in the presence of 5 mol% 2 in toluene at 70 1C did
not furnish indoline 6v.
2320 | Chem. Commun., 2014, 50, 2318--2320
This journal is ©The Royal Society of Chemistry 2014