Rhodium-Catalyzed Cycloisomerization of 2-Silylethynyl Phenols and Anilines via 1,2-Silicon Migration

Article abstract of DOI:10.1021/acs.orglett.6b00529

It has been established that a cationic rhodium(I)/BINAP complex catalyzes the cycloisomerization of 2-silylethynylphenols, leading to 3-silylbenzofurans, via 1,2-silicon migration. Similarly, the cycloisomerization of 2-silylethynylanilines, leading to 3-silylindoles, via 1,2-silicon migration was catalyzed by a cationic rhodium(I)/H₈-BINAP complex.

Full text of DOI:10.1021/acs.orglett.6b00529

Letter
pubs.acs.org/OrgLett
Rhodium-Catalyzed Cycloisomerization of 2‑Silylethynyl Phenols and
Anilines via 1,2-Silicon Migration
Hiroshi Kanno,†,‡ Kyosuke Nakamura,‡ Keiichi Noguchi,§ Yu Shibata,† and Ken Tanaka*,†,‡
†Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, O-okayama,
Meguro-ku, Tokyo 152-8550, Japan
§
‡Department of Applied Chemistry, Graduate School of Engineering, and Instrumentation Analysis Center, Tokyo University of
Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
S
* Supporting Information
ABSTRACT: It has been established that a cationic rhodium(I)/BINAP
complex catalyzes the cycloisomerization of 2-silylethynylphenols, leading to 3-
silylbenzofurans, via 1,2-silicon migration. Similarly, the cycloisomerization of 2-
silylethynylanilines, leading to 3-silylindoles, via 1,2-silicon migration was
catalyzed by a cationic rhodium(I)/H8−BINAP complex.
Experimental and theoretical mechanistic studies revealed that
he transition-metal-catalyzed cycloisomerization is a useful
Tmethod for the construction of complex carbocyclic and this cycloisomerization proceeds through allenyl ketone
intermediates.4 On the other hand, Lautens reported the
cycloisomerization of a 2-silylethynyl phenol via electrophilic
activation of the alkyne moiety by a highly electron-deficient
rhodium(I) complex as a catalyst (Scheme 1, middle).6
Importantly, this reaction afforded not a 3-silylbenzofuran but
a 2-silylbenzofuran without 1,2-silicon migration. In this paper,
we disclose the unprecedented catalytic cycloiosomerization of
2-silylethynyl phenols and anilines, leading to 3-silylbenzofur-
ans and 3-silylindoles, involving 1,2-silicon migration presum-
ably through rhodium vinylidene intermediates (Scheme 1,
bottom).7,8
heterocyclic frameworks.1 For the synthesis of heterocycles, the
intramolecular heterocyclization of alkynes and allenes is one of
the most useful and reliable methods.2 In order to synthesize
heterocycles with unusual substitution patterns, the hetero-
cyclization involving molecular rearrangements is attractive.3
For example, Gevorgyan reported the gold(I)-catalyzed cyclo-
isomerization of 4-silyl homopropargylic ketones to 3-
silylfurans involving 1,2-silicon migration (Scheme 1, top).4,5
Scheme 1
Recently, our research group reported the modular synthesis
of triphenylenes by the cationic rhodium(I)/H8−BINAP
complex-catalyzed [2 + 2 + 2] cycloaddition of bipheyl-linked
diynes with alkynes.9 In this cycloaddition, a silyl-substituted
propargyl alcohol was an excellent cycloaddition partner.9 This
result prompted us to investigate the reaction of bipheyl-linked
diyne and 2-silylethynyl phenol 1a. Surprisingly, not the
expected cycloaddition product but cycloisomerization product
2a involving 1,2-silicon migration was obtained as a major
product (Scheme 2).10
The reaction of 1a in the absence of bipheyl-linked diyne
under the above-mentioned reaction conditions afforded 2a as a
sole product, although the reaction was sluggish (Table 1, entry
1). Thus, the optimization of reaction conditions for the
cycloisomerization of 1a to 2a was examined. In this study,
active catalysts were prepared through removal of the cod
ligand by hydrogenation. Screening of bisphosphine ligands
(Figure 1, entries 1−6) revealed that the use of BINAP affords
2a in the highest yield (entry 1). The yields of 2a depend on
the electron density of biaryl bisphoshine ligands (entries 1−4).
Received: February 25, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b00529
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
increased the yield of 3a (entry 12). Other π-electrophilic
transition-metal complexes [RhCl(PPh3)3/AgBF4, [Ir(cod)2]-
BF4/BINAP, [Pd(MeCN)4](BF4)2/BINAP, PtCl2/2AgBF4,
AgBF4, AuCl(SMe2)/0.5BINAP, [Au(PPh3)]SbF6] were also
tested, while all of these were ineffective for this migratory
cycloisomerization.
Scheme 2
With the optimized reaction conditions in hand, we explored
the scope of this cycloisomerization as shown in Figure 2. With
Table 1. Optimization of Reaction Conditions for
a
Cycloisomerization of 2-Silylethynyl Phenol 1a
b
yield (%)
conv
entry
ligand
BINAP
X
conditions
(%)
2a
3a
1
2
3
4
5
6
7
8
9
BF4
BF4
BF4
BF4
BF4
BF4
SbF6
OTf
BArF
BF4
BF4
BF4
rt, 16 h
58
33
23
7
54
25
19
0
0
BIPHEP
H8−BINAP
Segphos
dppf
rt, 16 h
0
0
rt, 16 h
rt, 16 h
0
rt, 16 h
0
0
0
dppb
rt, 16 h
14
59
21
73
93
94
81
0
0
BINAP
BINAP
BINAP
BINAP
BINAP
−
rt, 16 h
53
8
0
rt, 16 h
0
c
4
rt, 16 h
63
90
40
7
0
d
10
80 °C, 1 h
80 °C, 16 h
80 °C, 16 h
0
ef
,
11
12
42
71
ef
,
a
[Rh(cod)2]X (0.010 mmol), ligand (0.010 mmol), 1a (0.050 mmol),
and CH2Cl2 (1.0 mL) were used. Active catalysts were prepared
b
c
through hydrogenation (1 atm, rt). Isolated yield. ArF = 3,5-
d
(CF3)2C6H3. [Rh(cod)2]BF4 (0.010 mmol), BINAP (0.010 mmol),
1a (0.20 mmol), and (CH2Cl)2 (1.0 mL) were used. CH2Cl)2 (1.0
mL) was used. Without hydrogenation.
Figure 2. Rhodium-catalyzed cycloisomerization of 2-silylethynyl
phenols 1a−m. [Rh(cod)2]BF4 (0.010−0.040 mmol), BINAP
(0.010−0.040 mmol), 1 (0.20 mmol), and (CH2Cl)2 (1.0 mL) were
used. The cited yields are of the isolated products.
e
f
respect to the substituents at the silicon atom (R1−R3), not
only dimethylphenyl (1a) but also tert-butyldimethyl (1b), tert-
butyldiphenyl (1c), diisopropylphenyl (1d), trimethyl (1e),
triethyl (1f), and triisopropyl (1g) groups could be employed
for this reaction, although high catalyst loadings were required
for sterically demanding substrates 1c and 1d. With respect to
the substituents at the benzene ring (R4−R6), various
substituted 3-silylbenzofurans 2h−m were obtained in high
yields, although high catalyst loadings were required.
Figure 1. Structures of bisphospnine ligands.
The reaction of germyl analogue 4 was also examined as
shown in Scheme 3.11 In this case, normal cycloisomerization
product 6 was obtained in higher yield than 1,2-germanium
migration product 5.
Screening of counteranions (entries 1 and 7−9) revealed that
the use of BF4 and SbF6 showed comparable good results
(entries 1 and 7). The use of BArF showed the highest
4
conversion of 1a, while the selectivity of 2a was lower than
those of BF4 and SbF6 (entry 9). Finally, when using BINAP as
a ligand and BF4 as a counteranion at elevated temperature (80
°C), high conversion of 1a was reached within 1 h using 5 mol
% of the catalyst to give 2a in 90% yield (entry 10).
Interestingly, when the catalyst was used without hydro-
genation, a 1:1 mixture of 2a and 3a was obtained (entry 11).
The use of [Rh(cod)2]BF4 without hydrogenation significantly
Scheme 3
B
DOI: 10.1021/acs.orglett.6b00529
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Next, we examined the rhodium-catalyzed cycloisomerization
Scheme 5
of 2-silylethynyl anilines 7 as shown in Figure 3.12 In this case,
Scheme 6
Based on these observations, a possible mechanism for the
rhodium-catalyzed cycloisomerization of 2-silylethynyl phenol 1
and aniline 7 is shown in Scheme 7. 2-Silylethynyl phenol 1
Scheme 7
Figure 3. Rhodium-catalyzed cycloisomerization of 2-silylethynyl
anilines 7a−j. [Rh(cod)2]BF4 (0.020−0.040 mmol), H8−BINAP
(0.020−0.040 mmol), 7 (0.20 mmol), and (CH2Cl)2 (8.0 mL) were
used. The cited yields are of the isolated products. a Isolated as a
mixture of 8a and 1H-indole. b (CH2Cl)2 (4.0 mL) was used.
H8−BINAP was found to be the best ligand and diluted
conditions were employed in order to suppress desilylation of
3-silylindole products 8. Similar to the cycloisomerization of 2-
silylethynyl phenols 1, varying substitution at the silicon atom
(R1−R3) and benzene rings (R4−R6) was tolerable. However,
yields of 1,2-silicon migration products 8 (3-silylindoles) were
moderate due to the formation of normal cycloisomerization
products 9 (2-silylindoles) as byproducts.13 Importantly, the
use of H8−BINAP in place of BINAP increased the yields of 3-
silylindoles 8 and decreased the yields of 2-silylindoles 9.14
In order to determine a possible reaction mechanism, the
following experiments were conducted. The reaction of 3b in
the presence of the rhodium catalyst did not afford 1,2-silicon
migration product 2b, and 3b was recovered unchanged
(Scheme 4).
reacts with a cationic rhodium(I) complex to generate rhodium
vinylidene B15 presumably through transition state A which is
stabilized by interaction between the phenol oxygen atom and
the migrating silicon atom.16 Subsequent oxycyclization affords
2. On the other hand, 3 can be generated via formation of
alkenyl-rhodium C followed by protonation. The same
mechanism can be applied to the formation of 8 and 9, while
a weak interaction between the aniline nitrogen atom and the
migrating silicon atom might decrease the yield of 1,2-silicon
migration product 8 and increase the yield of normal
cycloisomerization product 9. In addition, the more nucleo-
philic nature of the amino group than the hydroxy group results
in rapid cyclization to form 9 prior to the vinylidene formation.
The poor ability of the electron-rich rhodium(I)/H8−BINAP
catalyst toward the electrophilic alkyne activation might
account for suppression of the formation of normal cyclo-
isomerization products 9.
Scheme 4
The synthetic utility of 3-silylbenzofurans is demonstrated in
Scheme 8. Treatment of 2e with ICl afforded a new compound,
3-iodobenzofuran (10), which cannot be obtained by
iodination of benzofuran,17 in good yield.18
In conclusion, we have established that a cationic rhodium-
(I)/BINAP complex catalyzes cycloisomerization of 2-
silylethynylphenols, leading to 3-silylbenzofurans, via 1,2-silicon
migration. Similarly, cycloisomerization of 2-silylethynyl-
The reaction of a 1:1 mixture of 1h and 1i afforded a 1:1
mixture of 2h and 2j, and crossover products 2n and 2i were
not generated at all (Scheme 5). This result suggests that the
present cycloisomerization is an intramolecular process.
Finally, the reaction of 1a in the presence of MeOD
furnished 2a, in which the 2-position was partially deuterated
(Scheme 6).
C
DOI: 10.1021/acs.orglett.6b00529
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(g) Shiroodi, R. K.; Gevorgyan, V. Chem. Soc. Rev. 2013, 42, 4991.
(h) Crone, B.; Kirsch, S. F. Chem. - Eur. J. 2008, 14, 3514.
(4) Dudnik, A. S.; Xia, Y.; Li, Y.; Gevorgyan, V. J. Am. Chem. Soc.
2010, 132, 7645.
Scheme 8
(5) For other examples of the transition-metal-catalyzed intra-
molecular heterocyclization involving 1,2-silicon migration, see:
(a) Shiroodi, R. K.; Vera, C. I. R.; Dudnik, A. S.; Gevorgyan, V.
Tetrahedron Lett. 2015, 56, 3251. (b) Xia, Y.; Dudnik, A. S.; Li, Y.;
Gevorgyan, V. Org. Lett. 2010, 12, 5538. (c) Mochida, K.; Shimizu, M.;
Hiyama, T. J. Am. Chem. Soc. 2009, 131, 8350. (d) Dankwardt, J. W.
Tetrahedron Lett. 2001, 42, 5809.
anilines, leading to 3-silylindoles, via 1,2-silicon migration was
catalyzed by a cationic rhodium(I)/H8−BINAP complex.
Future work will focus on further exploration of the cationic
rhodium(I) complex-catalyzed cycloisomerization reactions
involving molecular rearrangements.
(6) Boyer, A.; Isono, N.; Lackner, S.; Lautens, M. Tetrahedron 2010,
66, 6468.
(7) A single example of the rhodium-catalyzed cycloisomerization of
a siloxy-linked 1,7-enyne was reported. The authors proposed that this
process proceeds via the rhodium vinylidene intermediate generated
through 1,2-silicon migration. See: Kim, H.; Lee, C. J. Am. Chem. Soc.
2005, 127, 10180.
(8) A single example of the rhodium-catalyzed cycloisomerization of
homopropargylic alcohols to dihydrofurans was reported. The authors
proposed that this process proceeds via the rhodium vinylidene
intermediate generated through 1,2-hydrogen migration. See: Trost, B.
M.; Rhee, Y. H. J. Am. Chem. Soc. 2003, 125, 7482.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b00529.
X-ray crystallographic file (CIF)
Experimental procedures and compound characterization
data (PDF)
(9) Murayama, K.; Sawada, Y.; Noguchi, K.; Tanaka, K. J. Org. Chem.
2013, 78, 6202.
(10) The gas-phase thermal cycloisomerization (750 °C) of 2-
trimethylsilylethynyl phenol to 3-trimethylsilylbenzofuran involving
1,2-silicon migration was reported; see: Barton, T. J.; Groh, B. L. J.
Org. Chem. 1985, 50, 158.
(11) For the transition-metal-catalyzed intramolecular heterocycliza-
tion involving 1,2-germanium migration, see: Seregin, I. V.;
Gevorgyan, V. J. Am. Chem. Soc. 2006, 128, 12050.
(12) For the transition-metal-catalyzed intramolecular heterocycliza-
tion of aniline derivatives involving molecular rearrangements, see:
(a) Yeung, C. F.; Chung, L. H.; Lo, H. S.; Chiu, C. H.; Cai, J.; Wong,
C. Y. Organometallics 2015, 34, 1963. (b) Abbiati, G.; Marinelli, F.;
Rossi, E.; Arcadi, A. Isr. J. Chem. 2013, 53, 856.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: ktanaka@apc.titech.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported partly by ACT-C from JST (Japan)
and Grants-in-Aid for Scientific Research (Nos. 26102004 and
25105714) from MEXT (Japan). We thank Takasago Interna-
tional Corporation for the gift of Segphos and H8−BINAP and
Umicore for generous support in supplying the rhodium
complex.
(13) The normal cycloisomerization products, 2-silylindoles 9, were
detected in ca. 10−30% yields as byproducts.
(14) See Table S1 of the Supporting Information.
(15) For the formation of rhodium vinylidenes from internal
silylacetylenes, see: (a) Katayama, H.; Onitsuka, K.; Ozawa, F.
Organometallics 1996, 15, 4642. (b) Werner, H.; Baum, M.; Schneider,
D.; Windmueller, B. Organometallics 1994, 13, 1089. (c) Werner, H.;
Schneider, D.; Schulz, M. J. Organomet. Chem. 1993, 451, 175.
(16) In the formation of rhodium vinylidene complexes from a 8-
quinolinolato rhodium(I) complex and terminal alkynes, stabilization
of the transition state by interaction between the oxygen atom and the
migrating hydrogen atom is proposed by the DFT calculation. See:
(a) Dang, Y.; Qu, S.; Wang, Z.-X.; Wang, X. Organometallics 2013, 32,
2804. For a report of the orginal reaction, see: (b) Kondo, M.; Kochi,
T.; Kakiuchi, F. J. Am. Chem. Soc. 2011, 133, 32.
(17) For examples of 2-lithiation followed by iodination of
benzofurans giving 2-iodobenzofurans, see: (a) Usui, S.; Hashimoto,
Y.; Morey, J. V.; Wheatley, A. E. H.; Uchiyama, M. J. Am. Chem. Soc.
2007, 129, 15102. (b) Zhang, H.; Larock, R. C. J. Org. Chem. 2002, 67,
7048.
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DOI: 10.1021/acs.orglett.6b00529
Org. Lett. XXXX, XXX, XXX−XXX