Rhodium-catalyzed intramolecular silylation of unactivated C(sp 3)-H bonds

Article abstract of DOI:10.1021/ol303353m

The treatment of a variety of hydrosilanes, each incorporating a benzylic C(sp³)-H bond, with a rhodium catalyst resulted in intramolecular dehydrogenative silylation. This silylation reaction was found to occur at typically unreactive C(sp³)-H bonds located at terminal positions on alkyl chains. Interestingly, the rhodium catalyst also promoted regioselective silylation at a site internal to an alkyl chain.

Full text of DOI:10.1021/ol303353m

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Rhodium-Catalyzed Intramolecular
Silylation of Unactivated C(sp3)ꢀH Bonds
Yoichiro Kuninobu,*,† Takahiro Nakahara, Hirotaka Takeshima, and Kazuhiko Takai*
Division of Chemistry and Biotechnology, Graduate School of Natural Science and
Technology, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530,
Japan
kuninobu@mol.f.u-tokyo.ac.jp; ktakai@cc.okayama-u.ac.jp
Received December 8, 2012
ABSTRACT
The treatment of a variety of hydrosilanes, each incorporating a benzylic C(sp3)ꢀH bond, with a rhodium catalyst resulted in intramolecular
dehydrogenative silylation. This silylation reaction was found to occur at typically unreactive C(sp3)ꢀH bonds located at terminal positions on
alkyl chains. Interestingly, the rhodium catalyst also promoted regioselective silylation at a site internal to an alkyl chain.
CꢀH bond functionalization is one of the most useful
and most versatile techniques for the synthesis of organic
molecules. As a result of the significant amount of research
recently applied to this aspect of synthetic chemistry, the
number of potential CꢀH bond transformations has
increased dramatically, especially in the case of C(sp2)ꢀH
bonds.1 In contrast, examples of transformations via
C(sp3)ꢀH bond activation are still rare.1 While there
have been several reports concerning C(sp3)ꢀH bond
transformations at benzylic2 and allylic3 CꢀH bonds and
at CꢀH bonds adjacent to a heteroatom,4 it is typically
difficult to achieve the functionalization of unactivated
C(sp3)ꢀH bonds.5 Such functionalizations are challenging
partly because the C(sp3)ꢀH bond is particularly strong
and also since it is difficult to control the regioselectivity of
the process. The few reports of successful functionalization
include the selective borylation of alkanes at terminal
carbons,6 transformations of C(sp3)ꢀH bonds adjacent
to quaternary carbon centers,7 C(sp3)ꢀH bond function-
alizations using a bidentate directing group,8 and others.9
† Present address: Graduate School of Pharmaceutical Sciences, The
University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
(1) For several recent reviews on transformations via CꢀH bond
activation, see: (a) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013. (b)
Jazzar, R.; Hitce, J.; Renaudat, A.; Sofack-Kreutzer, J.; Baudoin, O.
Chem.;Eur. J. 2010, 16, 2654. (c) Lyons, T. W.; Sanford, M. S. Chem.
Rev. 2010, 110, 1147.
(2) (a) Sakakura, T.; Tokunaga, Y.; Sodeyama, T.; Tanaka, M.
Chem. Lett. 1987, 2375. (b) Ishikawa, M.; Okazaki, S.; Naka, A.;
Sakamoto, H. Organometallics 1992, 11, 4135. (c) Espino, C. G.; Du
Bois, J. Angew. Chem., Int. Ed. 2001, 40, 598. (d) Kakiuchi, F.; Tsuchiya,
K.; Matsumoto, M.; Mizushima, E.; Chatani, N. J. Am. Chem. Soc.
2004, 126, 12792. (e) Li, Z.; Cao, L.; Li, C.-J. Angew. Chem., Int. Ed.
2007, 46, 6505. (f) Campeau, L.-C.; Schipper, D. J.; Fagnou, K. J. Am.
Chem. Soc. 2008, 130, 3266. (g) Zalatan, D. N.; Du Bois, J. J. Am. Chem.
Soc. 2009, 131, 7558. For several reviews, see: (h) Davies, H. M. L.;
Dick, A. R. Top. Curr. Chem. 2010, 292, 303. (i) Zalatan, D. N.; Du Bois,
J. Top. Curr. Chem. 2010, 292, 347.
(4) (a) Ishii, Y.; Chatani, N.; Kakiuchi, F.; Murai, S. Organometallics
1997, 16, 3615. (b) Ishii, Y.; Chatani, N.; Kakiuchi, F.; Murai, S.
Tetrahedron Lett. 1997, 38, 7565. (c) Chatani, N.; Asaumi, T.; Ikeda,
T.; Yorimitsu, S.; Ishii, Y.; Kakiuchi, F.; Murai, S. J. Am. Chem. Soc.
2000, 122, 12882. (d) Pastine, S. J.; Gribkov, D. V.; Sames, D. J. Am.
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Chem. Soc. 2006, 128, 14220. (e) Basle, O.; Li, C.-J. Org. Lett. 2008, 10,
3661. (f) Tsuchikama, K.; Kasagawa, M.; Endo, K.; Shibata, T. Org.
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Lett. 2009, 11, 1821. (g) Basle, O.; Li, C.-J. Chem. Commun. 2009, 4124.
(h) Yoshikai, N.; Mieczkowski, A.; Matsumoto, A.; Illies, L.;
Nakamura, E. J. Am. Chem. Soc. 2010, 132, 5568. For a recent review,
see: (i) Yoo, W.-J.; Li, C.-J. Top. Curr. Chem. 2010, 292, 281.
(5) Handbook of CꢀH Transformations; Dyker, G., Ed.; Wiley-VCH:
Weinheim, 2005; Vol. 2.
(6) (a) Chen, H.; Hartwig, J. F. Angew. Chem., Int. Ed. 1999, 38, 3391.
(b) Chen, H.; Schlecht, S.; Semple, T. C.; Hartwig, J. F. Science 2000,
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Murphy, J. M.; Lawrence, J. D.; Kawamura, K.; Incarvito, C.; Hartwig,
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r
10.1021/ol303353m
XXXX American Chemical Society

We have recently reported the rhodium-catalyzed syn-
thesis of silafluorene derivatives via SiꢀH and C(sp2)ꢀH
bond activation.10 On reacting a biphenylhydrosilane
bearing a methyl group at the ortho-position of the phenyl
group (A in Figure 1), the desired intramolecular C(sp2)ꢀH
bond silylation proceeded and the corresponding silafluo-
rene derivative B was formed in low yield. Interestingly,
silylation also proceeded at the C(sp3)ꢀH bond of the
methyl group, and 5,6-dihydrodibenzo[b,d]silane C was
obtained in 47% yield as the major product (Figure 1).
This result encouraged us toinvestigate benzylic C(sp3)ꢀH
bond silylation employing rhodium catalysis. We report
herein the rhodium-catalyzed silylation of a benzylic
C(sp3)ꢀH bond. This work further demonstrated that this
catalytic rhodium system can also promote the regio-
selective silylation of unactivated terminal and internal
C(sp3)ꢀH bonds.
the formation of 2,3-dihydro-1H-benzo[b]silole, 2a) in only
8% yield. However, on changing the catalyst to a mixture of
catalytic amounts of a rhodium complex, [RhCl(cod)]2, and
1,3-bis(diphenylphosphino)propane (dppp), the yield of 2a
increased dramatically and this product was obtained in 61%
yield (eq 1).11,12
We next investigated the variety of substrates to which
this reaction is applicable (Table 1). Usually, functionali-
zation of an unactivated C(sp3)ꢀH bond in tertiary alkyl
groups is readily accomplished, compared with primary
and secondary alkyl positions.7 Similarly, the silylation
reaction of the tertiary C(sp3)ꢀH bond of 1b proceeded
efficiently when applying our catalytic system, and the
Table 1. Rhodium-Catalyzed Intramolecular Silylation of
Unactivated C(sp3)ꢀH Bondsa
Figure 1. Rhodium-catalyzed silylation of aromatic C(sp2)ꢀH
and benzylic C(sp3)ꢀH bonds.
Compared with the biphenylhydrosilane A, the silyl
moiety of (2-methylbenzyl)hydrosilane (1a in eq 1) pos-
sesses significantly more freedom of motion. We therefore
anticipated that the transformation of 1a would be more
difficult for entropic reasons. Indeed, treatment of 1a with
a catalytic amount of a rhodium complex, [RhCl(PPh3)3],
gave the desired benzylic C(sp3)ꢀH silylation (resulting in
(7) C(sp3)ꢀH bonds adjacent to quaternary centers are relatively
easily functionalized because of entropic effects and the impossibility of
β-hydride elimination. See: (a) Watanabe, T.; Oishi, S.; Fujii, N.; Ohno,
H. Org. Lett. 2008, 10, 1759. (b) Wang, D.-H.; Wasa, M.; Giri, R.; Yu,
J.-Q. J. Am. Chem. Soc. 2008, 130, 7190. (c) Chaumontet, M.; Piccardi,
R.; Audic, N.; Hitce, J.; Peglion, J.-L.; Clot, E.; Baudoin, O. J. Am.
Chem. Soc. 2008, 130, 15157. (d) Neumann, J. J.; Rakshit, S.; Droge, T.;
Glorius, F. Angew. Chem., Int. Ed. 2009, 48, 6892. (e) Wasa, M.; Engle,
K. M.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 9886. (f) Stowers, K. J.;
Fortner, K. C.; Sanford, M. S. J. Am. Chem. Soc. 2011, 133, 6541.
(8) (a) Zaitsev, V. G.; Shabashov, D.; Daugulis, O. J. Am. Chem. Soc.
2005, 127, 13154. (b) Reddy, B. V. S.; Reddy, L. R.; Corey, E. J. Org.
Lett. 2006, 8, 3391. (c) Shavashov, D.; Daugulis, O. J. Am. Chem. Soc.
2010, 132, 3965. (d) Hasegawa, N.; Charra, V.; Inoue, S.; Fukumoto, Y.;
Chatani, N. J. Am. Chem. Soc. 2011, 133, 8070. (e) Ano, Y.; Tobisu, M.;
Chatani, N. J. Am. Chem. Soc. 2011, 133, 12984.
(9) (a) Hitce, J.; Retailleau, P.; Baudoin, O. Chem.;Eur. J. 2007, 13,
792. (b) Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.;
Saunders, L. B.; Yu, J.-Q. J. Am. Chem. Soc. 2007, 129, 3510. (c)
€
Nakanishi, M.; Katayev, D.; Besnard, C.; Kundig, E. P. Angew. Chem.,
Int. Ed. 2011, 50, 7438. (d) Anas, S.; Cordi, A.; Kagan, H. B. Chem.
Commun. 2011, 11483. (e) Saget, T.; Lemouzy, S. J.; Cramer, N. Angew.
€
Chem., Int. Ed. 2012, 51, 2238. (f) Katayev, D.; Nakanishi, M.; Burgi, T.;
a 1.0 M. b Isolated yield. c 1,2-Bis(diphenylphosphino)benzene
(4.5 mol %) was added as a phosphine ligand. d 4 h. e [RhCI(cod)]2
(2.5 mol %), 1,2-bis(diphenylphosphino)benzene (7.5 mol %). f GC
yield. g 0.08 M, [RhCI(cod)]2 (6.0 mol %), 1,2-bis(diphenylphosphino)-
benzene (18 mol %), and 3,3-dimethyl-1-butene (2.0 equiv) were added
as a phosphine ligand and hydrogen acceptor.
€
Kundig, E. P. Chem. Sci. 2012, 3, 1422. (g) Sofack-Kreutzer, J.; Martin,
N.; Renaudat, A.; Jazzar, R.; Baudoin, O. Angew. Chem., Int. Ed. 2012,
51, 10399. (h) Wasa, M.; Chan, K. S. L.; Zhang, Z.-G.; He, J.; Miura,
M.; Yu, J.-Q. J. Am. Chem. Soc. 2012, 134, 18570. See also refs 7a
and 7e.
(10) Ureshino, T.; Yoshida, T.; Kuninobu, Y.; Takai, K. J. Am.
Chem. Soc. 2010, 132, 14324.
B
Org. Lett., Vol. XX, No. XX, XXXX

corresponding five-membered compound 2b was provided
in 80% yield (entry 1). Treatment of (2-ethylphenyl)-
dimethylsilane (1c) with catalytic amounts of [RhCl(cod)]2
and dppp gave 1,1-dimethyl-2,3-dihydro-1H-benzo[b]silole
(2c) in 66% yield (entry 2).13ꢀ17 This result shows that the
silylation of primary unactivated alkyl C(sp3)ꢀH bonds
can also be achieved. The silylation reaction also pro-
ceeded when using 1d, a hydrosilane with two phenyl
groups on the silicon atom (entry 3). When employing
substrates bearing a methoxy group on the aromatic ring
or a naphthalene moiety as the aromatic ring, the corre-
sponding silylated products 2e and 2f were obtained in
reasonable yields (entries 4 and 5). In the above syntheses,
the aromatic ring can be considered to play an important
role by fixing the relative conformational positions of the
hydrosilyl and C(sp3)ꢀH reactive sites. However, our
results demonstrate that this intramolecular silylation
reaction also proceeded without the presence of aromatic
rings. The silacyclopentane (2g) was produced in 43%
yield when tributylsilane (1g) was treated with a catalytic
amount of the rhodium catalyst (entry 6).18ꢀ20 Interest-
ingly, the silylation reaction also proceeded at the internal
aliphatic position of 1h, and the corresponding dihydro-
benzosilole 2h was obtained in 37% yield (entry 7). This
result is important because many previous reactions pro-
ceeded only at the terminal aliphatic positions. It is worthy
of special mention that, in entry 7, the regioselectivity was
controlled completely.21
The proposed mechanism for aliphatic C(sp3)ꢀH bond
silylation ispresented inScheme1. Instep(1), the oxidative
addition of the SiꢀH bond of 1 to a rhodium center takes
place, resulting in SiꢀH bond activation. After the forma-
tion of intermediate D, there are two possible pathways.
One possible route (2) involves σ-bond metathesis between
the RhꢀH and CꢀH bonds of intermediate D via the
elimination of H2 to give intermediate E. The alternate
pathway (3) consists of the oxidative addition of the
C(sp3)ꢀH bond of the alkyl chain (CꢀH bond activation)
followed by reductive elimination (4) to produce inter-
mediate E with the formation of H2. After the formation of
intermediate E, reductive elimination (5) occurs to give
product 2 and regenerate the rhodium catalyst.
Scheme 1. Proposed Mechanism for Rhodium-Catalyzed
Regioselective Silylation of C(sp3)ꢀH Bonds
(11) Investigation of several hydrogen acceptors: norbornene, 59%;
cyclohexene, 49%; 3,3-dimethyl-1-butene, 44%; methyl acrylate, 0%. In
this reaction, the yield of 2a decreased by adding a hydrogen acceptor.
(12) There have been several reports on silylation of benzylic CꢀH
bonds. See: Mita, T.; Michigami, K.; Sato, Y. Org. Lett. 2012, 14, 3462.
See also ref 2d.
(13) The structure of 2c was determined by comparison of its 1H and
13C NMR and GC-MS spectra with those of the same compound
prepared by another method. See: Benkeser, R. A.; Mozdzen, E. C.;
Muench, W. C.; Roche, R. T.; Siklosi, M. P. J. Org. Chem. 1979, 44,
1370.
(14) RhCl(PPh3)3 (3.0 mol %), 22%; [Rh(cod)]BF4 (3.0 mol %) þ dppp
(9.0 mol %), 25%; (1,4-dioxane, 180 °C, 24 h); [IrCl(cod)]2 (1.5 mol %) þ
dppp (4.5 mol %), 16%; Pd(PPh3)4 (3.0 mol %, 150 °C), 9%; Pd2(dba)3
(1.5 mol %), 0%. Product 2c was not obtained: Pd/C, Pd/CaCO3, RhH-
In summary, we have succeeded in the rhodium-catalyzed
silylation of a benzylic C(sp3)ꢀH bond. In addition, we have
demonstrated the regioselective intramolecular silylation of
unactivated terminal and internal C(sp3)ꢀH bonds using this
rhodium-based catalytic system. Since it is usually difficult to
functionalize an unactivated C(sp3)ꢀH bond regioselectively,
especially at internal positions along an alkyl chain, these
results are important. In addition, this is the first example of
regioselective silylation of a C(sp3)ꢀH bond at a location
internal to an alkyl chain. It is our hope that these novel
silylation reactions will provide useful insights into the future
possibilities of this aspect of synthetic organic chemistry.
(CO)(PPh3)3, Rh4(CO)12, Ru3(CO)12, Ir4(CO)12, Re2(CO)10
.
(15) Investigation of several combinations of catalytic amounts of
[RhCl(cod)]2 and several phosphine (and amine) ligands: 1,2-bis-
(diphenylphosphino)ethane (dppe), 50%; 1,2-bis(diphenylphosphino)-
butane (dppb), 16%; 1,2-bis[di(pentafluorophenyl)phosphine]ethane,
56%; 1,10-bis(diphenylphosphine)ferrocene (dppf), 44%; 1,2-bis-
(diphenylphosphino)benzene, 66%; bis(2-biphenylyl)phenylphosphine,
19%; BINAP, 38%; TMEDA, 7%; 1,10-phenanthroline, 21%.
(16) Investigation of several solvents: cyclopentylmethylether
(CPME), 68%; dibutylether, 15%; toluene, 65%; p-xylene, 29%; mesi-
tylene, 28%; octane, 5%; neat, 10%. Product 2c was not obtained: 1,1,2-
trichloroethane, DMF.
Acknowledgment. This work was partially supported
by the Ministry of Education, Culture, Sports, Science,
and Technology of Japan.
(17) Investigation of reaction temperature: 150 °C, 5%; 135 °C, 4%.
(18) The structure of 2g was determined by comparison of its 1H and
13C NMR and GC-MS spectra with those of the same compound
prepared by another method. See ref 10.
(19) For an example of intramolecular dehydrogenative silylation at
the terminal position of the alkyl chain, see: Tsukada, N.; Hartwig, J. F.
J. Am. Chem. Soc. 2005, 127, 5022.
(20) During our investigation, Hartwig’s group reported iridium-
catalyzed intramolecular silylation at the terminal positions of alkyl
chains. See: Simmons, E. M.; Hartwig, J. F. Nature 2012, 483, 70.
(21) The obtained silapentane derivatives are precursors of 1,4-diols
by oxidation. See: Reference 20. See also: Kuznetsov, A.; Gevorgyan, V.
Org. Lett. 2012, 14, 914.
Supporting Information Available. General experimen-
tal procedures and characterization data for C(sp3)ꢀH
silylated products 2. This material is available free of
charge via the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. XX, No. XX, XXXX
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