General and practical one-pot synthesis of dihydrobenzosiloles from styrenes

Article abstract of DOI:10.1021/ol203428c

A one-pot synthesis of dihydrobenzosiloles from styrenes has been developed. The reaction involves the nickel-catalyzed hydrosilylation of styrene with diphenylsilane, followed by the iridium-catalyzed dehydrogenative cyclization. This method is efficient for both electron-rich and -deficient styrenes and exhibits good functional group tolerance, as well as excellent regioselectivity. The forming dihydrobenzosiloles can be efficiently converted into valuable benzosiloles or 2-hydroxyphenethyl alcohols.

Full text of DOI:10.1021/ol203428c

ORGANIC
LETTERS
2012
Vol. 14, No. 3
914–917
General and Practical One-Pot Synthesis
of Dihydrobenzosiloles from Styrenes
Alexey Kuznetsov and Vladimir Gevorgyan*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061, United States
vlad@uic.edu
Received December 22, 2011
ABSTRACT
A one-pot synthesis of dihydrobenzosiloles from styrenes has been developed. The reaction involves the nickel-catalyzed hydrosilylation of
styrene with diphenylsilane, followed by the iridium-catalyzed dehydrogenative cyclization. This method is efficient for both electron-rich
and -deficient styrenes and exhibits good functional group tolerance, as well as excellent regioselectivity. The forming dihydrobenzosiloles can be
efficiently converted into valuable benzosiloles or 2-hydroxyphenethyl alcohols.
Dehydrogenative coupling of the SiÀH bond with aro-
matic CÀH bondsisa powerful method forthe synthesis of
valuable aryl and hetaryl silanes. In recent years, several
methods for SiHÀCH coupling have been developed
(Figure 1). Thus, in 2005 Hartwig showed the possibility of
the formation of dihydrobenzosilole from dimethylphe-
nethylsilane via an intramolecular platinum-catalyzed de-
hydrogenative cyclization reaction (eq 1).1 However, the
reaction required harsh conditions, and the scope of this
approach toward dihydrobenzosiloles was not established.
Later, Falck reported2 a milder iridium-catalyzed intermo-
lecular silylation of electron-rich aromatic heterocycles
(eq 2). Then, Takai reported3 the rhodium-catalyzed synth-
esis of dibenzosiloles from biarylhydrosilanes (eq 3). Very
recently, Hartwig showed4 that Falck’s conditions can ef-
ficiently be used for ortho- CÀH silylation of benzyl alcohol
derivatives (eq 4). In 2009, Kawashima reported5 the Lewis
acid mediated intramolecular sila-FriedelÀCrafts reaction
leading to dibenzosiloles (eq 5). Dihydrobenzosiloles hold
promise in becoming useful synthons for organic chemistry6
(vide infra); however, to date, there are no efficient methods
for their synthesis.7 Herein, we wish to report a practical
and general one-pot procedure for the synthesis of dihydro-
benzosiloles 3 from styrenes 1 through the Ni-catalyzed
hydrosilylation, followed by the Ir-catalyzed dehydrogena-
tive cyclization (eq 6).
We aimed at developing a method for the synthesis of
dihydrobenzosiloles via β-hydrosilylation of styrenes with
dihydrosilanes, followed by dehydrogenative cyclization
of the formed product. First, we turned our attention to
(5) Furukawa, S.; Kobayashi, J.; Kawashima, T. J. Am. Chem. Soc.
2009, 131, 14192.
(1) Tsukada, N.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 5022.
(2) Lu, B.; Falck, J. R. Angew. Chem., Int. Ed. 2008, 47, 7508.
(3) Ureshino, T.; Yoshida, T.; Kuninobu, Y.; Takai, K. J. Am. Chem.
Soc. 2010, 132, 14324.
(4) Simmons, E. M.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132,
17092.
(6) For an example of hydrogenation of dihydrobenzosilole, see:
Benkeser, R. A.; Mozdzen, E. C.; Muench, W. C.; Roche, R. T.; Siklosi,
M. P. J. Org. Chem. 1979, 44, 1370.
(7) For selected examples of synthesis of dihydrobenzosiloles, see: (a)
Belzner, J.; Dehnert, U.; Ihmels, H. Tetrahedron 2001, 57, 511. (b) Ando,
W.; Sekiguchi, A. J. Org. Chem. 1980, 45, 5286. See also refs 1 and 6.
r
10.1021/ol203428c
Published on Web 01/24/2012
2012 American Chemical Society

However, a combination of triphenylphosphine with
Ni(cod)2 gave the desired hydrosilane 2a in high yield
and regioselectivity (entry 10).
Table 1. Table 1. Optimization of the Reaction Conditions for
Ni-Catalyzed Hydrosilylation of Styrene with Diphenysilanea
GC yield, %
entry
cat.
β-
R-
Ph3SiH
1
NiCl2•(PCy3)2
NiCl2•dppe
NiCl2•dppf
NiCl2•dppp
NiCl2•(PPh3)2
NiBr2•(PPh3)2
NiBr2•(PPh3)2
NiBr2
À
À
34
8
2
6
13
3
3
10
55
87
90
3
4
37
<2
<2
<1
À
11
<2
<1
<1
À
5
Figure 1. Methods for SiHÀCH coupling.
6
7b
8
92 (87)c
À
hydrosilylation of styrenes, as the first step of the proposed
sequence. Although several methods for hydrosilylation of
styrene with diphenylsilane using Au,8 Zr,9 Yb,10 and Rh11
complexes exist, methods employing cheap and readily avail-
able catalysts are still in demand. On the other hand, it is
known that nickel(II) salts with phosphine ligands are effec-
tive catalysts for hydrosilylation of olefins.12 Since there are
no reports on nickel-catalyzed β-hydrosilylation of styrene
with dihydrosilanes, we verified the possibility of hydrosily-
lation of styrene with diphenylsilane in the presence of nickel
catalysts (Table 1). When 5 mol % NiCl2•(PCy3)2 was em-
ployed, only triphenylsilane, a product of disproportionation
of diphenylsilane,13 was formed (entry 1). Using 5 mol %
NiCl2•dppe, the desired hydrosilylated product 2a was ob-
tained in 6% yield (entry 2). Other nickel catalysts, such
as NiCl2•dppf and NiCl2•dppp, provided 2a in 10% and
55% yields, respectively (entries 3, 4). We were pleased to
find that NiCl2•(PPh3)2 and NiBr2•(PPh3)2 gave 2a in high
yield and high regioselectivity (entries 5À7). When NiBr2
without triphenylphosphine was used, no hydrosilylated
product was formed (entry 8). Employment of phosphine-
free Ni(cod)2 resulted in the mixture of regioisomers (entry 9).
9
10d
Ni(cod)2
53
89
30
<2
6
Ni(cod)2/PPh3
<1
a Conditions: 5 mol % cat., 0.2 mmol of styrene, 0.22 mmol of
Ph2SiH2 in 0.2 mL of THF were stirred at 80 °C for 6 h under a N2
atmosphere. The reaction was monitored by GC-MS analysis. b 2 mol %
cat. was used. The reaction was analyzed after 1 h. c Isolatedyield is given
in parentheses. d 5 mol % cat. and 20 mol % PPh3 were used.
After a convenient method for β-hydrosilylation of
styrene with diphenylsilane was established, we searched
for efficient conditions for intramolecular dehydrogenative
cyclization. It was found that, under Falck’s conditions,2
the hydrosilane 2a underwent smooth dehydrogenative
cyclization into the dihydrobenzosilole 3a. Moreover, it
was found that the dehydrocyclization can be performed
in a one-pot manner after completion of the hydrosilyla-
tion step to produce dihydrobenzosilole 3a in 86% over-
all yield.
Next we examined the scope of this one-pot transforma-
tion (Table 2). It was found that this method is quite gen-
eral, as diverse styrenes, possessing MeO, Me, F, Cl, and
CO2Me groups in ortho-, meta- and para-positions, were
well tolerated under the reaction conditions to give the cor-
responding dihydrobenzosiloles 3in good yields. Generally,
when meta-substituted styrenes were used, dehydrocycliza-
tion occurred at the least hindered para-position to the
substituent. Only when a small group, such as fluorine, was
employed, a 2:1 mixture of para- and ortho-cyclized prod-
ucts 3i was obtained. In the case of ortho-methylstyrene,
36 h were required for the completion of the dehydrocycli-
zation step toward 3g.
(8) For selected examples of Au-catalyzed hydrosilylation of styrene
with Ph2SiH2, see: (a) Corma, A.; Gonzalez-Arellano, C.; Iglesias, M.;
Sanchez, F. Angew. Chem., Int. Ed. 2007, 46, 7820. (b) Debono, N.;
Iglesias, M.; Sanchez, F. Adv. Synth. Catal. 2007, 349, 2470.
(9) For an example of Zr-catalyzed hydrosilylation of styrene with
Ph2SiH2, see: Takahashi, T. J. Am. Chem. Soc. 1991, 113, 8564.
(10) For an example of Yb-catalyzed hydrosilylation of styrene with
Ph2SiH2, see: Takaki, K.; Sonoda, K.; Kousaka, T.; Koshoji, G.;
Shishido, T.; Takehira, K. Tetrahedron Lett. 2001, 42, 9211.
(11) For selected examples of Rh-catalyzed hydrosilylation of styrene
with Ph2SiH2, see: (a) Nielsen, L.; Skrydstrup, T. J. Am. Chem. Soc.
2008, 130, 113145. (b) Betley, T. A.; Peters, J. C. Angew. Chem., Int. Ed.
2003, 42, 2385.
(12) For examples of Ni(II) and Ni(0) catalyzed hydrosilylation of
olefins, see: (a) Belyakova, Z. V.; Pomerantseva, M. G.; Efimova, L. A.;
Chernyshev, E. A.; Storozhenko, P. A. Rus. J. Gen. Chem. 2010, 80, 728.
(b) Gareau, D.; Sui-Seng, C.; Groux, L. F.; Brisse, F.; Zargarian, D.
Organometallics 2005, 24, 4003. (c) Yamamoto, K.; Hayashi, T.;
Uramoto, Y.; Ito, R.; Kumada, M. J. Organomet. Chem. 1976, 118, 331.
(13) For examples of Rh-catalyzed disproportionation of diphenyl-
silane, see: (a) Rodenberg, L.; Davis, C. W.; Yao J. Am. Chem. Soc.
2001, 123, 5120. (b) Chang, L. S.; Corey, J. Y. Organometallics 1989, 8,
1885.
Org. Lett., Vol. 14, No. 3, 2012
915

Table 2. Scope of the One-Pot Hydrosilylation Dehydrocycli-
zation Reactiona
Scheme 1. HydrosilylationÀDehydrocyclization Reaction of
R-Substituted Styrenes
was found for the rates of cyclization of meta-substituted
styrenes: MeO < Me < H<Cl < CO2Me. Likewise, intra-
molecular competitive cyclization experiments of 2u and 2v
indicated a similar reactivity trend (Scheme 2). Hence, cycli-
zation of 2u, possessing a Me- group in one of the aromatic
rings, preferentially occurred at the unsubstituted ring,
whereas there was a slight preference for cyclization into
the Cl-substituted aromatic ring in 2v. Thus, in all cases, the
reaction preferentially occurs at the electron-deficient CÀH
bond, thereby supporting the CÀH activation path rather
than the electrophilic metalation pathway.4 Furthermore,
the performed intermolecular kinetic isotope effect studies
of 2a and 2a-d515 revealed kH/kD = 1.6, which suggests that
cleavage of the aromatic CÀH bond may occur at the rate-
determining step.16
Scheme 2. Intermolecular Competitive Cyclization
a Conditions: 2 mol % Ni cat., 0.50 mmol of styrene, 0.53 mmol of
Ph2SiH2 in 0.5 mL of THF were stirred at 80 °C for 1 h under a N2
atmosphere. Then, 2 mol % Ir cat., 4 mol % dtbpy, 0.6 mmol of
norbornene, and 2.0 mL of THF were added. Reaction was stirred at
80 °C for 12 h.
Next, we examined the possibility of employment of this
one-pot method for synthesis ofsubstituteddihydrobenzo-
siloles (Scheme 1). To this end, hydrosilylation of R-
substituted styrenes was examined. Unfortunately hydro-
silylation reaction of R-methyl- 1s and R-phenyl styrene 1t in
the presence of a NiBr2•(PPh3)2 catalyst system was not
effective. However, the corresponding hydrosilylated pro-
ducts were obtained in high yields employing a Lewis acid
catalyst, B(C6F5)3.14 Subsequently, after removing B(C6F5)3
and the solvent, the dehydrocyclization step was performed
using standard dehydrogenative coupling conditions. Thus,
3-methylbenzosilole 3s and 3-phenyldehydrobenzosilole 3t
were obtained using this semi-one-pot procedure in 79% and
76% yields, respectively (Scheme 1).
In order to gain some insight into the mechanism of the
dehydrocyclization reaction, we first performed an inter-
molecular competitive cyclization study. It was found that
the substrates possessing electron-withdrawing groups at the
aromatic ring cyclized faster then those possessing electron-
donating groups. Thus, the following reactivity trend
Based on the above-mentioned observations, the follow-
ing mechanistic pathways were proposed (Scheme 3). First,
the iridium species undergo oxidative addition into the SiÀH
bond of hydrosilane 2 with formation of iridium hydride A.
Hydrometalation of the double bond of norbornene gives
intermediate B, which then undergoes insertion into the
aromatic CÀH bond to give intermediate C (Path A, similar
to Falck’s mechanism2). The following reductive elimination
of norbornane gives intermediate D. Alternatively (Path B),
the concerted metalationÀdeprotonation of the intermediate
B through the transition state E17 can occur to give the same
intermediate D upon elimination of the norbornane. The
reductive elimination from D leads to the cyclized product 3
and regenerates the iridium catalyst.
After developing a practical method for the synthesis of
dihydrobenzosiloles from styrenes, the initial studies of
(15) See Supporting Information for details.
(16) (a) Livendahl, M.; Echavarren, A. M. Isr. J. Chem. 2010, 50, 630.
(b) Wei, Y.; Kan, J.; Wang, M.; Su, W.; Hong, M. Org. Lett. 2009, 11,
3346.
(17) For a very recent study on the CMD-type mechanism in the Ir-
catalyzed CÀH arylation, see: Garcia-Melchor, M.; Gorelsky, S. I.;
Woo, T. K. Chem.;Eur. J. 2011, 17, 13847.
(14) For B(C6F5)3-catalyzed hydrosilylation of alkenes, see: Rubin,
M.; Schwier, T.; Gevorgyan, V. J. Org. Chem. 2002, 67, 1936.
916
Org. Lett., Vol. 14, No. 3, 2012

their synthetic utility were performed. It was found that
compounds 3a, 3s, and 3t in the presence of DDQ can be ef-
fectively oxidized into valuable benzosiloles 418 (Scheme 4).
Expectedly, oxidation of 3-phenyl derivative 3t is more
facile than that of 3-methyl derivative 3s, which in turn is
more reactive than the unsubstituted dihydrobenzosilole
3a. It has also been shown that dihydrobenzosiloles 3a, 3s,
and 3t can readily be converted into 2-hydroxyphenethyl
alcohols 5 in 79À87% yield when treated with tert-butylper-
oxide and TBAF. By application of standard Mitsunobu-
type reaction conditions, 2-hydroxyphenethyl alcohol
5a was smoothly transformed into dihydrobenzo-
furan 6a.
Scheme 3. Proposed Mechanistic Pathways
In summary, we have developed a general and practical
method for a one-pot synthesis of synthetically valuable
dihydrobenzosiloles from styrenes. The method implies a
nickel-catalyzed hydrosilylation reaction followed by the
irridium-catalyzed dehydrogenative cyclization process.
The obtaineddihydrobenzosiloles can bereadily converted
into benzosiloles or 2-hydroxyphenethyl alcohols.
Acknowledgment. We thank the National Institutes of
Health (GM-64444 and 1P50 GM-086145) for financial
support of this work.
Scheme 4. Further Transformations of Dihydrobenzosiloles
Supporting Information Available. Detailed experimen-
tal procedures and characterization data for all new
compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
(18) (a) Wong, W. W. H.; Hooper, J. F.; Holmes, A. B. Aust. J. Chem.
2009, 62, 393. (b) Wong, W. W. H.; Holmes, A. B. Adv. Polym. Sci. 2008,
212, 85. (c) Tamao, K.; Uchida, M.; Izumizawa, T.; Furukawa, K.;
Yamaguchi, S. J. Am. Chem. Soc. 1996, 118, 11974.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 3, 2012
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