Construction of benzosiloles, six- and eight-membered silacyclic skeletons, via a Pd-catalyzed intramolecular Mizoroki-Heck reaction of vinylsilanes

Article abstract of DOI:10.1021/ol302040j

A variety of silacycles including benzosiloles, six- and eight-membered silacyclic skeletons, were efficiently synthesized via a Pd-catalyzed intramolecular Mizoroki-Heck reaction of vinylsilanes.

Full text of DOI:10.1021/ol302040j

ORGANIC
LETTERS
2012
Vol. 14, No. 17
4572–4575
Construction of Benzosiloles, Six- and
Eight-Membered Silacyclic Skeletons,
via a Pd-Catalyzed Intramolecular
MizorokiÀHeck Reaction of Vinylsilanes
Kunbing Ouyang,†,‡ Yun Liang,§ and Zhenfeng Xi*,‡
Beijing National Laboratory for Molecular Sciences (BNLMS), and Institute of
Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, China,
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry
of Education, College of Chemistry, Peking University, Beijing 100871, China, and
Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research,
Ministry of Education, Hunan Normal University, Changsha, Hunan 410081, China
zfxi@pku.edu.cn
Received July 23, 2012
ABSTRACT
A variety of silacycles including benzosiloles, six- and eight-membered silacyclic skeletons, were efficiently synthesized via a Pd-catalyzed
intramolecular MizorokiÀHeck reaction of vinylsilanes.
Silicon possesses some crucial differences from carbon
(e.g., covalent radius and electronegativity). Thus, when a
carbon atom isreplaced by a silicon atom (theC/Si switch),
the chemical and physicochemical properties of an organic
compound may be changed dramatically.1À7 For example,
silacyclopentadiene (often named silole) as organic material
of electronic and opto-electronic devices demonstrates great-
er superiority compared to its carbon-analogue, cyclo-
pentadiene.3,4 In particular, the C/Si switch strategy has
been applied successfully for odorant design5,6 and pharma-
ceutical applications.7 Furthermore, specific properties
can be expected from totally new silicon-containing
† Institute of Chemistry, CAS.
(2) For examples on the synthesis of silacyclic compounds, see: (a)
Greene, M. A.; Prevost, M.; Tolopilo, J.; Woerpel, K. A. J. Am. Chem.
Soc. 2012, 134, 12482–12484. (b) Franc-ois, C.; Boddaert, T.; Durandetti,
M.; Querolle, O.; van Hijfte, L.;Meerpoel, L.;Angibaud, P.; Maddaluno,
J. Org. Lett. 2012, 14, 2074–2077. (c) Lazareva, N. F.; Albanov, A. I.;
Shainyan, B. A.; Kleinpeter, E. Tetrahedron 2012, 68, 1097–1104. (d)
Seiser, T.; Cramer, N. Angew. Chem., Int. Ed. 2010, 49, 10163–10167. (e)
Hernandez, D.; Nielsen, L.; Lindsay, K. B.; Lopez-Garcia, M. A.;
Bjerlund, K.; Skrydstrup, T. Org. Lett. 2010,12, 3528–3531. (f) Blaszykowski,
C.; Brancour, C.; Dhimane, A. C.; Tensterbank, L.; Malacria, M. Eur. J. Org.
Chem. 2009, 11, 1674–1678. (g) Lim, Y. M.; Lee, M. E. Organometallics
2008, 27, 1000–1004. (h) Wei, X.; Taylor, R. J. K. Tetrahedron Lett. 2003,
44, 7143–7146. (i) Mansel, S.; Rief, U.; Prosenc, M.-H.; Kirsten, R.;
Brintzinger, H.-H. J. Organomet. Chem. 1996, 512, 225–236. (j) Alper,
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‡ Peking University.
§ Hunan Normal University.
(1) For reviews on the synthesis and properties of silacyclic com-
pounds, see: (a) Wang, L.; Duan, Z. Chin. Sci. Bull. 2012in press. (b)
Cusak, A. Chem.;Eur. J. 2012, 18, 5800–5824. (c) Bracegirdle, C.;
Anderson, E. A. Chem. Soc. Rev. 2010, 39, 4114–4129. (d) Rousseau,
G.; Blanco, L. Tetrahedron 2006, 62, 7951–7993. (e) Liu, J.; Zhang, S.;
Zhang, W.-X.; Xi, Z. Prog. Chem. 2009, 21, 1475–1486. (f) Liu, J.;
Zhang, W.-X.; Xi, Z. Chin. J. Org. Chem. 2009, 29, 491–503. (g)
Fensterbank, L.; Malacria, M.; Sieburth, S. M. Synthesis 1997, 8, 813–
854. (h) Dubac, J.; Laporterie, A.; Manuel, G. Chem. Rev. 1990, 90, 215–
263. (i) Hermanns, J.; Schmidt, B. J. Chem. Soc., Perkin Trans. 1 1999,
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r
10.1021/ol302040j
Published on Web 08/10/2012
2012 American Chemical Society

compounds, of which the carbon analogues cannot be
synthesized or are very difficult to make. Thus, as a
consequence, the development of synthetic methods for
silacyclic compounds remains one of the most important
frontiers in synthetic chemistry.1À7
Vinylsilaneis animportant building blockfor construct-
ing CÀC bonds along with desilylation of the remaining
silyl moiety.8À10 As shown in Scheme 1, vinylsilanes have
been used in the Hiyama cross-coupling reaction to make
CÀC bonds using the silyl group as a leaving group.8
Conceptually, the MizorokiÀHeck reaction is a good
choice to make CÀC bonds while the silyl group remains
in the product.8a,9,10 Thus, silacyclic skeletons can be
constructed via an intramolecular MizorokiÀHeck reac-
tion of vinylsilanes (Scheme 1).9 However, it is rarely
reported that vinylsilane participates in the MizorokiÀ
Heck reaction.9,10 Among all those examples reported on
intermolecular MizorokiÀHeck reactions, formation of new
CÀC bonds at the β-position of vinylsilane is predominate.10
To the best of our knowledge, there is only one example of
the formation of a CÀC bond at the R-position of
vinylsilane.9 Meanwhile, this is also the only report of an
intramolecular MizorokiÀHeck reaction leading to a five-
membered silacyclic ring as a byproduct in <30% yield.9
(3) For reviews on siloles, see: (a) Shimizu, M.; Hiyama, T. Synlett
2012, 23, 973–989. (b) Corey, J. Y. Adv. Organomet. Chem. 2011, 59, 1–
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1998, 22, 3693–3702.
Scheme 1. Hiyama Cross-Coupling and MizorokiÀHeck
Reaction of Vinylsilanes; Construction of Silacycles via a
Intramolecular MizorokiÀHeck Reaction
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W.; Wei, J.; Xi, Z. Angew. Chem., Int. Ed. 2012, 51, 1934–1937. (b) Liang,
Y.; Zhang, S.; Xi, Z. J. Am. Chem. Soc. 2011, 133, 9204–9207. (c)
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I. D.; Wong, K. S.; Tang, B. Z. Macromolecules 2010, 43, 4921–4936. (f)
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We have recently reported the synthesis of silole deriva-
tives via Pd-catalyzed cleavage of the SiÀMe bond and the
formation of six-membered silacycles via Pd-catalyzed
cleavage of the silyl C(sp3)ÀH bond (Scheme 2).4a,b,11 As
a continuation of our interest in this transition-metal cata-
lyzed cleavage of the SiÀC(sp3) bond and the silyl C(sp3)ÀH
bond, we investigated silyl compounds of different substi-
tuents on the silicon center. Interestingly, as given in
Scheme 2, when compound 1a substituted with a SiMe3
group was changed to compound 1b substituted with a
SiMe2(CHdCH2) group, neither product 2 nor product 4
was obtained under the same reaction conditions. Instead, a
new compound 3 obviously formed via the intramolecular
MizorokiÀHeck reaction, which was obtained in 28% and
50% yields, respectively. This new finding prompted us to
study this intramolecular MizorokiÀHeck reaction. Here,
we report our results on the synthesis of various silacycles
including benzosiloles, six- and eight-membered silacyclic
skeletons, via a Pd-catalyzed intramolecular MizorokiÀ
Heck reaction. Either the R- or β-positioned CÀC bond
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Org. Lett., Vol. 14, No. 17, 2012
4573

forming reaction proceeded highly selectively depending on
the structures of the products.
(2.5 mol %), XPhos (10 mol %), LiOt-Bu (3 equiv), toluene,
120 °C, 12 h. Under these optimized conditions, the six-
membered silacyclic compound 3 was obtained in 90%
isolated yield (entry 8). Obviously, this compound 3 is
formed via the intramolecular MizorokiÀHeck reaction at
the R-position of the vinylsilane moiety. No β-positioned
CÀC coupling product was observed. This perfect R-posi-
tioned selectivity is probably due to the higher stability of
the six-membered silacyclic ring.
Scheme 2. Different Reactions around a Silyl Group
With the above optimized reaction conditions in hand,
we tested various bromides containing vinylsilane moi-
eties, such as 2-bromo(vinylsilyl)benzenes 1cÀe. As given
in Scheme 3, benzosilole derivatives 5 and 6 could be
obtained in good ioslated yields. A ladder-type π-conju-
gated molecule 7 could also be prepared in 75% isolated
yield by this reaction from 1e. Benzosiloles are important
compounds in materials chemistry.3,4 This method pro-
vides an efficient alternative route to such compounds. It is
obvious that in these cases the intramolecular MizorokiÀ
Heck reaction takes place at the β-position of the vinyl-
silane moiety. No R-positioned CÀC coupling product was
obtained. This perfect β-positioned selectivity is probably
due to the stable silole rings.
Scheme 3. Formation of Benzosiloles via the Intramolecular
MizorokiÀHeck Reaction at the β-Position of the Vinylsilane
Moiety
Table 1. Optimization of Reaction Conditions (see Supporting
Information for details)
yield of
entry
[Pd]
PdCl2
ligand
base
solvent
3 (%)a
1
t-Bu3P
XPhos
t-Bu3P
XPhos
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
42
2
PdCl2
57
3
Pd2(dba)3
Pd2(dba)3
30
4
73
5
Pd(PPh3)4 t-Bu3P
28
6
Pd(PPh3)4 XPhos
26
7
Ab
A
A
A
A
A
A
A
A
A
A
t-Bu3P
XPhos
PCy3
(69)
92(90)
58
8
9
10
11
12
13
14
15
16
17
DPEPhos LiOt-Bu
46
none
LiOt-Bu
44
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
NaOt-Bu toluene
23
KOt-Bu
NEt3
toluene
toluene
CH2Cl2
CH3CN
DMF
trace
trace
61
In contrast to the substrates 1cÀ1e which underwent the
intramolecular MizorokiÀHeck reaction at the β-position
of the vinylsilane moiety, substrates 1fÀ1l afforded their
R-positioned CÀC coupling products containing a six- or
eight-membered silacyclic ring (Scheme 4), which are
similar to the reaction of 1b. As shown in Scheme 4,
compound 1f, which contains a silyl group substituted
with a methyl, phenyl, and vinyl, undergoes a similar
intramolecular MizorokiÀHeck reaction, affording its
corresponding six-membered silacyclic product 8 in 87%
LiOt-Bu
LiOt-Bu
LiOt-Bu
59
48
a GC yield (C12H26 as internal standard), isolated yields are in
parentheses. b A: [PdCl(π-allyl)]2.
First, various reaction conditions were screened (see
Table 1 and Supporting Information for details). Optimal
reaction conditions were realized as follows: [PdCl(π-allyl)]2
4574
Org. Lett., Vol. 14, No. 17, 2012

Scheme 4. Formation of Six- and Eight-Membered Silacyclic
Rings via the Intramolecular MizorokiÀHeck Reaction at the
R-Position of the Vinylsilane Moiety
Scheme 5. Formation of Six-Membered Oxasilacyclic Rings
via the Intramolecular MizorokiÀHeck Reaction at the
R- or β-Position of the Vinylsilane Moiety
optimized reaction conditions, compound 1m afforded
the six-membered oxasilacycle 15 in 84% isolated yield
as the sole product. Interestingly, compound 1n also gave a
six-membered oxasilacycle 16 as the sole product. Ob-
viously, these two substrates 1m and 1n reacted at different
positions of the vinylsilane moiety, which could be attrib-
uted to the stability of the six-membered rings.
In summary, we developed an efficient Pd-catalyzed
intramolecular MizorokiÀHeck reaction of vinylsilanes
to construct benzosiloles, six- and eight-membered silacyc-
lic skeletons. The stability of the formed silacyclic rings
controlled the reaction sites (R- or β-position) of the
vinylsilane moieties. This method provides an efficient
route to benzosilole derivatives, six- and eight-membered
silacyclic compounds.
Acknowledgment. This work was supported by the
Natural Science Foundation of China and the 973 Pro-
gram (2012CB821600).
isolated yield. The biphenyl derivatives 1g and 1h and the
binaphthal derivative 1i could all be used to give their
corresponding six-membered silacyclic products 9À11,
respectively. Notably, the eight-membered silacyclic com-
pounds 12À14 could be also obtained highly efficiently via
the above reaction. For all these cases, the R-positioned
selectivity was exclusive.
Supporting Information Available. Experimental de-
tails and scanned NMR spectra of all new products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Oxasilacycles are compounds of synthetic inter-
est.1b,c,2a,c,d,f As given in Scheme 5, under the above
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 17, 2012
4575