Palladium-catalyzed enantioselective desymmetrization of silacyclobutanes: Construction of silacycles possessing a tetraorganosilicon stereocenter

Article abstract of DOI:10.1021/ja208621x

A palladium-catalyzed desymmetrization of alkyne-tethered silacyclobutanes to give silacycles possessing a tetraorganosilicon stereocenter has been developed, and high chemo- and enantioselectivities have been achieved by the use of a newly synthesized ch

Full text of DOI:10.1021/ja208621x

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Palladium-Catalyzed Enantioselective Desymmetrization of
Silacyclobutanes: Construction of Silacycles Possessing a
Tetraorganosilicon Stereocenter
Ryo Shintani,* Kohei Moriya, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
S Supporting Information
b
silacyclobutanes for the intramolecular ring-expansion reaction
under the catalysis of a chiral palladium complex.
ABSTRACT: A palladium-catalyzed desymmetrization of
alkyne-tethered silacyclobutanes to give silacycles posses-
sing a tetraorganosilicon stereocenter has been developed,
and high chemo- and enantioselectivities have been achieved
by the use of a newly synthesized chiral phosphoramidite
ligand.
As a starting point, we prepared alkyne-tethered silacyclobu-
tane 1a and conducted a reaction in the presence of PdCp-
(η3-C3H5) (5 mol %) and phosphoramidite ligand (S,R,R)-L112,13
(10 mol %) in THF at 60 °C.14,15 Under these conditions, the
reaction proceeded smoothly to give a 35/65 mixture of tricyclic
compound 2a and bicyclic compound 3a in 97% combined yield,
and the 2a was obtained with 43% ee (Table 1, entry 1).16 The
use of the diastereomeric ligand (S,S,S)-L213 improved the
enantioselectivity of 2a to 76% ee with some increase in the
formation of 2a over 3a (55/45; entry 2), and the 3,30-dimethyl-
ated ligand (S,S,S)-L317 showed significantly higher selectivity
toward 2a (2a/3a = 87/13) with the same level of enantioselec-
tivity (74% ee; entry 3). On the other hand, higher enantio-
selectivity of 2a (84% ee) was observed by changing the 1,
10-binaphthyl backbone of (S,S,S)-L2 to 5,50,6,60,7,70,8,80-octa-
hydro-1,10-binaphthyl [(S,S,S)-L4],18 with 2a/3a = 73/27 (entry 4).
In the hope of merging the chemoselectivity with (S,S,S)-L3 and
the enantioselectivity with (S,S,S)-L4, we employed the newly
synthesized ligand (S,S,S)-L5 bearing methyl groups at the 3- and
30-positions of the octahydrobinaphthyl moiety and found that
this ligand did indeed improve both the product ratio and the
enantioselectivity (2a/3a = 94/6, 2a ee = 87%; entry 5). Further
optimization revealed that the reaction in toluene instead of THF
turned out to be slightly more favorable with respect to both
chemo- and enantioselectivity (entry 6 vs entry 5), and the best
result was obtained by conducting the reaction in toluene at
30 °C, which gave 2a in high yield with high selectivity (2a/3a =
97/3, 2a ee = 92%; entry 7).
Under the optimized conditions, several para- or meta-sub-
stituted aryl groups are tolerated on the silicon atom of 1, giving
the corresponding silacycles 2 with high selectivity (2/3 = 96/
4ꢀ98/2, 87ꢀ95% ee; Table 2, entries 1ꢀ4), but the aryl group
with an ortho-substituent leads to somewhat lower chemo- and
enantioselectivity (2e/3e = 86/14, 71% ee; entry 5). With regard
to the substituent on the alkyne terminus, various aryl groups as
well as an alkenyl group can be incorporated to give products 2
with similarly high efficiency (2/3 = 91/9ꢀ98/2, 84ꢀ93% ee;
entries 6ꢀ10).19 In addition, the tether between the silicon and
the alkyne can be altered as shown in entries 11ꢀ15, although the
selectivities become lower with an alkyl tether (2o/3o = 69/31,
75% ee; entry 15). The absolute configuration of 2n obtained in
entry 14 was determined to be R by X-ray crystallographic
symmetric catalysis has been a topic of extensive research in
A
synthetic organic chemistry for decades, primarily focusing
on the construction of carbon stereocenters.1 In contrast, the
development of catalytic enantioselective methods to create
chiral silicon stereocenters has been much less explored despite
the wide utility of organosilicon compounds, and the typical
synthetic methods for these compounds rely on the use of
stoichiometric amounts of chiral reagents.2 Unlike the formation
of carbon stereocenters, because of the difficulty of employing
addition reactions to siliconꢀcarbon or siliconꢀheteroatom
double bonds,3 the available strategy is mostly restricted to
substitution reactions. In fact, most of the existing catalytic
asymmetric methods are based on hydrosilylation of ketones4 or
alcoholysis5 using diorganosilanes (R1R2SiH2, R1 ¼ R2), sub-
stituting one of the enantiotopic hydrogen atoms by an alkoxy
group. Other than these approaches, only two studies have been
carried out under transition-metal catalysis as far as we are aware:
rhodium-catalyzed double intramolecular hydrosilylation of
olefins to prepare axially chiral spirosilanes6 and iridium-
catalyzed SiꢀH insertion with diazo compounds to prepare
triorganosilanes.7 As a new entry for catalytic asymmetric
construction of chiral organosilanes with a stereogenic silicon
atom, herein we describe the development of a palladium-
catalyzed enantioselective desymmetrization of silacyclobutanes
to give silacycles possessing a tetraorganosilicon stereocenter.
In 1975, Sakurai and Imai reported that 1,1-dimethylsilacyclo-
butane reacts with several alkynes in the presence of a palladium
catalyst to give ring-expanded 1,1-dimethyl-1-sila-2-cyclohexenes.8
Oshima and Utimoto revisited the same reactions in 1991 and
found that 1-sila-2-cyclohexenes are obtained with concomitant
formationofring-opened allyl(vinyl)silanederivatives.9 Sincethen,
several transition-metal-catalyzed synthetic reactions using silacy-
clobutanes have been reported,10,11 but none of the existing
methods have been applied to asymmetric catalysis to date. In
this context, we decided to explore the possibility of constructing
tetraorganosilicon stereocenters by the use of alkyne-tethered
Received: September 13, 2011
Published: September 21, 2011
r
2011 American Chemical Society
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|

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Table 1. Palladium-Catalyzed Desymmetrization of Silacy-
clobutane 1a: Optimization
Table 2. Palladium-Catalyzed Desymmetrization of Silacy-
clobutanes 1: Scope
yield of
2a + 3a (%)a
ratio of
2a/3a a
ee of 2a
(%)b
entry
ligand
solvent
1
2
3
4
5
6
7c
(S,R,R)-L1
(S,S,S)-L2
(S,S,S)-L3
(S,S,S)-L4
(S,S,S)-L5
(S,S,S)-L5
(S,S,S)-L5
THF
97
99
96
99
95
91
96d
35/65
55/45
87/13
73/27
94/6
43
76
74
84
87
88
92
THF
THF
THF
THF
toluene
toluene
95/5
97/3
a Determined by 1H NMR analysis. b Determined by chiral HPLC on a
Chiralpak OT(+) column with 98:2 hexane/2-propanol after complete
separation of 2a from 3a. c The reaction was conducted for 48 h at 30 °C.
d Isolated yield.
analysis with Cu Kα radiation after recrystallization from chlor-
obenzene/nonane (Figure 1).20
The present catalytic reactions can also be conducted on a
preparative scale with a reduced catalyst loading. Thus, 0.50 g of
1a was fully converted to 2a/3a in the ratio of 97/3 (2a ee = 92%)
in the presence of a 3 mol % loading of the palladium catalyst, and
treatment of the crude mixture with activated carbon followed by
trituration with hexane readily provided pure compound 2a
without chromatographic purification in 84% yield (0.42 g) with
99% ee (eq 1).21 The highly enantioenriched 2a thus obtained
could undergo further functionalization while retaining the
stereochemical integrity. For example, hydroboration of 2a with
BH3 THF took place in a regio- and diastereoselective fashion,
3
and successive acidic aqueous workup provided the correspond-
ing organoboronic acid 4 with contiguous two-carbon and one-
silicon stereocenters in 74% yield (eq 2).20ꢀ22 In addition,
diastereoselective hydrogenation of 2a smoothly proceeded as
well in the presence of a catalytic amount of Pd(OH)2 on carbon
to give compound 5 in 70% yield, which was converted to
triorganohydrosilane 6 in 86% yield by removal of the 4-meth-
oxyphenyl group on the silicon in 5 via treatment with triflic acid
followed by reduction with LiAlH4 (eq 3).2,7
1
c
a Isolated yields. b Determined by H NMR analysis. Determined by
chiral HPLC with hexane/2-propanol after complete separation of 2
from 3. d Isolated yield of 2. The reaction was conducted at 40 °C.
e
f Determined by 1H NMR analysis after chromatographic purification on
silica gel.
Proposed catalytic cycles for the reaction of 1a in the presence
of Pd/(S,S,S)-L5 are illustrated in Scheme 1. Thus, oxidative
addition of a carbonꢀsilicon bond of silacyclobutane 1a to
palladium(0) gives 1-pallada-2-silacyclopentane A.9,23 This then
undergoes intramolecular insertion of the alkyne to give 1-palla-
da-4-sila-2-cycloheptene B, reductive elimination of which leads
to the formation of compound 2a along with regeneration of
palladium(0). In contrast, β-hydrogen elimination from inter-
mediate B gives alkenylpalladium hydride species C, and succes-
sive reductive elimination results in the formation of compound
3a. Because a carbonꢀcarbon bond-forming reductive elimina-
tion is known to become more facile with sterically demanding
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Scheme 1. Proposed Catalytic Cycles for the Palladium-
Catalyzed Desymmetrization of Silacyclobutane 1a ([Pd] =
Pd/(S,S,S)-L5, Ar = 4-MeOC6H4)
by the use of a newly synthesized chiral phosphoramidite ligand.
We have also demonstrated that the present catalysis is similarly
effective for the intermolecular process. Future studies will be
directed toward further expansion of the reaction scope and
mechanistic investigations to understand the origin of the
stereoselectivity.
Figure 1. X-ray crystal structure of (R)-2n (Flack parameter = 0.012;
H atoms have been omitted for clarity).
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures, com-
b
pound characterization data, and X-ray data (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
shintani@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
’ ACKNOWLEDGMENT
Support was provided in part by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan (the Global COE Program
“Integrated Materials Science” at Kyoto University).
ligands on palladium,24 the observed trend of chemoselectivity
between compounds 2a and 3a in Table 1 can be explained by the
bulkiness of the phosphoramidite ligands, with the highest
selectivity toward 2a being achieved with ligand (S,S,S)-L5.
We have also begun to explore an intermolecular variant of the
present asymmetric catalysis,8,9 and in our preliminary experiment,
the reaction of 1-(4-methoxyphenyl)-1-methylsilacyclobutane (7)
with dimethyl acetylenedicarboxylate proceeded smoothly under
the same conditions as in Table 2 in the presence of Pd/(S,S,S)-L5
to give 1-sila-2-cyclohexene derivative 8 with a silicon stereogenic
center exclusively in 94% yield with 90% ee (eq 4).
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In summary, we have developed a palladium-catalyzed asym-
metric ring expansion of alkyne-tethered silacyclobutanes to
obtain silacycles possessing tetraorganosilicon stereocenters,
and high chemo- and enantioselectivities have been achieved
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COMMUNICATION
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