Catalytic enantioselective synthesis of alkenylhydrosilanes

Article abstract of DOI:10.1002/anie.201207361

Asymmetric silanes: A synthesis of nonracemic alkenylhydrosilanes has been developed based on the desymmetrization of a dihydrosilane through alkenylation with an alkyne using an asymmetric catalyst. The alkenylhydrosilane product can be used as a versatile chiral building block for other functionalized nonracemic silanes through the stereoselective conversion of its hydride and/or alkenyl moiety. Copyright

Full text of DOI:10.1002/anie.201207361

Angewandte
Chemie
DOI: 10.1002/anie.201207361
Chiral Silanes
Catalytic Enantioselective Synthesis of Alkenylhydrosilanes**
Kazunobu Igawa, Daisuke Yoshihiro, Nobumasa Ichikawa, Naoto Kokan, and
Katsuhiko Tomooka*
Nonracemic silanes possessing a silicon stereocenter have
structural similarity to their carbon congeners, but show
substantial differences in their physical and electronic proper-
ties. Therefore, nonracemic silanes have attracted attention in
the fields of synthetic,[1] material,[2] and bioorganic chemis-
try.[3] Despite their potential importance, nonracemic silanes
are unavailable in nature, and therefore the development of
an efficient asymmetric method for their preparation is
eagerly awaited.[1] Among the several possible methods for
the asymmetric synthesis of chiral silanes, desymmetrization
of achiral silanes A would be the most rational approach
(Scheme 1). Previously, we had developed asymmetric syn-
nonracemic silanes.[5] However, these approaches require
stoichiometric to sub-stoichiometric chiral sources, along with
an excess of reagents. Thus, the development of a more
efficient catalytic approach to chiral silanes is highly desir-
able.
To this end, we recently examined the asymmetric syn-
thesis of alkenylhydrosilane 5 from dihydrosilane 4 (a variant
of A, where X = H) by desymmetric hydrosilylation with an
alkyne [Eq. (1)].[6–8] As a result, we found that the reaction
catalyzed by the complex of phosphonite 6, which is derived
from tetraaryl-1,3-dioxolane-4,5-dimethanol (taddol) and Pt0,
realizes this desymmetrization.[9–13] This new approach allows
for the catalytic synthesis of chiral alkenylhydrosilanes 5 in an
enantioselective fashion with high atom efficiency. Further-
more, we have achieved the transformation of alkenylhydro-
silane 5 into functional chiral silanes such as silanol 3 in
enantioenriched form, through the stereoselective conversion
of the hydride and/or alkenyl moieties of 5. Herein, we
provide the details of our novel approach and the synthetic
value of the resulting chiral silanes.
Scheme 1. Our previous approaches to nonracemic silanols.
thetic approaches to chiral silanols 3 from diarylsilanes 1 (X =
Ar) and dialkoxysilanes 2 (X = OR) through diastereoselec-
tive and enantioselective desymmetrization, respectively.[4]
Furthermore, we have demonstrated the synthetic versatility
of 3 as a chiral building block for a variety of functionalized
We started our investigations with the readily available
PhtBuSiH2 (4a) and 3-hexyne as substrates. In this approach,
there is concern about the possible overreaction of 5aa to
afford dialkenylsilane 7aa [Eq. (2); dba = dibenzylideneace-
tone, dppp = bis(diphenylphosphino)propane, ND = not
[*] Dr. K. Igawa, Prof. Dr. K. Tomooka
Institute for Materials Chemistry and Engineering
Kyushu University, Kasuga, Fukuoka 816-8580 (Japan)
E-mail: ktomooka@cm.kyushu-u.ac.jp
Homepage: http://www.cm.kyushu-u.ac.jp/tomooka
D. Yoshihiro, N. Ichikawa
Interdisciplinary Graduate School of Engineering Sciences
Kyushu University (Japan)
N. Kokan
Department of Applied Chemistry
Tokyo Institute of Technology (Japan)
[**] This research was supported by JSPS (KAKENHI 24350048,
23655086), Global COE Program (Kyushu Univ.), Management
Expenses Grants for National Universities Corporations, MEXT:
Project of Integrated Research on Chemical Synthesis, and the
Nagase Science and Technology Foundation. We thank the
Takasago International Corp. for their gift of chiral bidentate
phosphine ligands, Y. Kawasaki (Kyushu Univ.) for his technical
support, and Y. Tanaka (IMCE, Kyushu Univ.) for the HRMS
measurements.
detected]. To know whether proper choice of the ligand can
prevent this overreaction, we performed an achiral version of
the reaction using a catalytic amount of [Pt(dba)3] with PPh3
or dppp as a representative monodentate or bidentate ligand,
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201207361.
Angew. Chem. Int. Ed. 2012, 51, 12745 –12748
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
12745

.
Angewandte
Communications
respectively.[14] These reactions showed a sharp contrast: the
reaction using PPh3 afforded the desired 5aa in excellent yield
(95%) in 5 h at 258C, but the one with dppp afforded 5aa in
low yield (32%) along with the dialkenylsilane 7aa (5%) and
recovered 4a (48%) after 24 h at the same temperature.
On the basis of these results, we surveyed a number of
monodentate chiral phosphorus ligands and found that
taddol-derived phosphonites 6 are the ligands of choice. The
reaction with [Pt(dba)3] (1 mol%) and phosphonite 6a
(2 mol%; Ar= Ph) gave 5aa in 74% yield, in an enantioen-
riched form (37% ee, (À); Table 1, entry 1).[15,16] The absolute
stereochemistry of (À)-5aa was determined to be the
S configuration by transforming it into a stereochemically
Table 2: Scope and limitation of the asymmetric hydrosilylation of
dihydrosilane 4.[a]
Entry
4
Alkyne 6[b] T [8C]
R
5
Yield [%]
ee [%][c,d]
1
4a
4a
4a
4a
4a
4a
4b Et
4b Et
4c
4c
Me
Me
nPr
nPr
Me
nPr
6b
6b
6b
6b
6d 25
6d 25
6d 25
6d
6b
6b
25
5ab 63[e]
43 (+)(S)
2[f]
3
À30
5ab 56[e] (72)[g] 72 (+)(S)
25
5ac
5ac
82[e]
46 (À)(S)
4[f]
5
6
À30
21[e] (57)[g] 78 (À)(S)
5ab 90[e]
30 (À)(R)
46 (+)(R)
60 (+)
5ac
5b
5b
5c
78[e]
Table 1: Enantioselective hydrosilylation of dihydrosilane 4a.[a]
7
95[h]
8[i]
9[j]
10[f]
0
88[h]
68 (+)
Et
Et
25
À30
83[k]
67 (À)
5c
28[k] (58)[g]
86 (À)
[a] Unless otherwise noted, the reaction was performed with alkyne
(1 equiv), [Pt(dba)3] (1 mol%), and 6 (2 mol%) in toluene at 258C for
3 h. [b] Prepared from corresponding (R,R)-taddol and PhPCl2.
[c] Determined by HPLC analysis using a chiral stationary phase. [d] Sign
of [a]D and absolute stereochemistry. [e] Determined by 1H NMR analysis
using anisole as an internal standard. [f] The reaction was run for 7 days.
[g] Yields based on recovered 4. [h] Determined by GLC analysis using
n-tetradecane as an internal standard. [i] The reaction was run for 24 h.
[j] The reaction was run for 2 days. [k] Yield of isolated product.
Entry
6[b]
Ar
T [8C]
5aa
Yield [%]
ee [%][c,d]
1
2
3
4
6a
6b
6c
6d
6b
6b
Ph
25
25
25
25
0
74[e]
37 (À)(S)
50 (À)(S)
45 (+)(R)
54 (+)(R)
64 (À)(S)
82 (À)(S)
4-MeOC6H4
3,5-Me2C6H3
3,5-(CF3)2C6H3
4-MeOC6H4
4-MeOC6H4
69[e]
83[e]
96[f]
5[g]
6[i]
72[f] (84)[h]
47[f] (81)[h]
À30
[a] Unless otherwise noted, the reaction was performed with 3-hexyne
(1 equiv), [Pt(dba)3] (1 mol%), and 6 (2 mol%) in toluene at 258C for
3 h. [b] Prepared from the corresponding (R,R)-taddol and PhPCl2.
[c] Determined by HPLC analysis using a chiral stationary phase. [d] Sign
of [a]D and absolute stereochemistry. [e] Yield of isolated product.
[f] Determined by GLC analysis using n-tetradecane as an internal
standard. [g] The reaction was run for 24 h. [h] Yields based on recovered
4a. [i] The reaction was run for 7 days.
applicable to the hydrosilylation of substrates 4b (R1 =
2,6-Me2C6H3, R2 = Me) and 4c (R1 = 2,6-Me2C6H3, R2 = Ph)
as well (entries 7–10).[18] In particular, the reaction of 4c with
3-hexyne in the presence of 6b afforded excellent enantiose-
lectivities: 67% ee at 258C and 86% ee at À308C (entries 9
and 10).
The nonracemic hydrosilanes 5 can be converted into
a variety of optically active silanes through transformation of
the hydride and/or alkene moieties. Regarding the conversion
defined chiral silane (see below). The enantioselectivity was
significantly improved to 50% ee by the use of 6b (Ar=
4-MeOC6H4) as the ligand (entry 2). Furthermore, ligand 6,
which bears a 3,5-disubstituted phenyl moiety, provided the
opposite stereoselectivities: the reactions with 6c (Ar= 3,5-
Me2C6H3) and 6d (Ar= 3,5-(CF3)2C6H3) afforded (R)-5aa in
45% ee and 54% ee, respectively (entries 3 and 4). After
optimization of the reaction conditions, we found that the
reactions with 6b at low temperatures afford high enantio-
selectivities: 64% ee at 08C and 82% ee at À308C (entries 5
and 6), although the reactions are slow. These results are the
first examples of the enantioselective synthesis of an alke-
nylhydrosilane.
This enantioselective hydrosilylation has a broad sub-
strate scope. The reactions of 4a with 2-butyne and 4-octyne
also afforded nonracemic silanes with moderate to good
enantioselectivities: (S)-5ab, 43% ee at 258C and 72% ee at
À308C; (S)-5ac, 46% ee at 258C, and 78% ee at À308C
(Table 2, entries 1–4).[17] Again, a switch in selectivity was
observed when the ligand was changed from phosphonite 6b
to 6d (entries 5 and 6). Furthermore, the reaction was
À
of the hydride moiety, we successfully converted the Si H
À
bond into a Si C bond in nonracemic alkenylhydrosilane (À)-
5aa (53% ee) and obtained alkenylsilane (+)-8 by the
[Pt(dvds)]-catalyzed (dvds = 1,1,3,3,-tetramethyl-1,3-divinyl-
disiloxane) hydrosilylation with 1-butene, without loss of
enantiopurity (Scheme 2, 69% yield, 53% ee).
The absolute stereochemistry of (À)-5aa and (+)-8 was
adequately determined by comparison with the separately
synthesized authentic sample, as follows. Initially, we pre-
pared stereochemically defined hydrosilane (S)-10 (59% ee)
from enantioenriched silanol (R)-3a by our previously
reported procedure.[5b] Pt-catalyzed hydrosilylation of (S)-10
and 3-hexyne gave (+)-8 in 59% ee. Compound (+)-8 was
determined to have an S configuration based on the retention
of stereochemistry at silicon in the Pt-catalyzed hydrosilyla-
tion of nonracemic hydrosilanes with alkenes[19] and
alkynes[20] that has been reported by the groups of Sommer
and Brook, respectively. Hence, it was revealed that (À)-5aa
has an S configuration.
12746 www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 12745 –12748

Angewandte
Chemie
6, 1469; e) A. Weickgenannt, M. Mewald, M. Oestreich, Org.
Biomol. Chem. 2010, 8, 1497; f) L.-W. Xu, L. Li, G.-Q. Lai, J.-X.
Jiang, Chem. Soc. Rev. 2011, 40, 1777.
[2] For a representative review on the application of nonracemic
silanes to material chemistry, see: Y. Kawakami, Y. Kakihana, O.
Ooi, M. Oishi, K. Suzuki, S. Shinke, K. Uenishi, Polym. Int. 2009,
58, 279, and references therein.
[3] For a representative review on the application of nonracemic
silanes to bioorganic chemistry, see: W. Bains, R. Tacke, Curr.
Opin. Drug Discovery Dev. 2003, 6, 526, and references therein.
[4] a) K. Tomooka, A. Nakazaki, T. Nakai, J. Am. Chem. Soc. 2000,
122, 408; b) K. Igawa, J. Takada, T. Shimono, K. Tomooka, J.
Am. Chem. Soc. 2008, 130, 16132; c) A. Nakazaki, J. Usuki, K.
Tomooka, Synlett 2008, 2064.
[5] The stereoselective transformation of nonracemic silanols has
been reported; see: a) A. Nakazaki, T. Nakai, K. Tomooka,
Angew. Chem. 2006, 118, 2293; Angew. Chem. Int. Ed. 2006, 45,
2235; b) K. Igawa, N. Kokan, K. Tomooka, Angew. Chem. 2010,
122, 740; Angew. Chem. Int. Ed. 2010, 49, 728.
Scheme 2. Transformation and determination of absolute stereochem-
istry of alkenylhydrosilane 5aa. [a] This work. DMAP=4-(dimethyami-
no)pyridine, dvds=1,1,3,3,-tetramethyl-1,3-divinyldisiloxane, Ret=
retention of configuration.
[6] Limited methods for the catalytic enantioselective synthesis of
nonracemic silanes from dihydrosilanes have been reported. For
À
dehydrogenative Si O coupling with alcohols, see: a) R. J. P.
Corriu, J. J. E. Moreau, Tetrahedron Lett. 1973, 14, 4469; b) D. R.
Schmidt, S. J. OꢁMalley, J. L. Leighton, J. Am. Chem. Soc. 2003,
Furthermore, we have succeeded in the stereoselective
conversion of the alkenyl group in a nonracemic alkenylsilane
into an OH group by our previously reported ozone oxidation
method.[21] The reaction of alkenylsilane (S)-8 (53% ee) with
ozone afforded peroxysilane (R)-9 as a diastereomeric mix-
ture, which was then converted into nonracemic silanol (R)-
3a through base-mediated b-elimination, although the enan-
tiopurity was slightly decreased (3a; 88% yield over 2 steps,
44% ee). From this stereochemical outcome, it was revealed
À
125, 1190; for Si O bond-forming hydrosilylation with ketones,
see: c) R. J. P. Corriu, J. J. E. Moreau, J. Organomet. Chem. 1974,
64, C51; d) T. Hayashi, K. Yamamoto, M. Kumada, Tetrahedron
Lett. 1974, 15, 331; e) R. J. P. Corriu, J. J. E. Moreau, J. Organo-
met. Chem. 1975, 85, 19; f) T. Ohta, M. Ito, A. Tsuneto, H.
Takaya, J. Chem. Soc. Chem. Commun. 1994, 2525; for metal
À
carbenoid insertion into the Si H bond, see: g) Y. Yasutomi, H.
Suematsu, T. Katsuki, J. Am. Chem. Soc. 2010, 132, 4510.
[7] Enantioselective methods for the synthesis of nonracemic silanes
from achiral tetraorganosilanes have been reported. For the
asymmetric desymmetrization of bis(hydroxymethyl)silane and
bis(acetoxymethyl)silane with enzymatic esterification and
hydrolysis, see: a) A. H. Djerourou, L. Blanco, Tetrahedron
Lett. 1991, 32, 6325; b) A. H. Djerourou, L. Blanco, Phosphorus
Sulfur Silicon Relat. Elem. 1999, 149, 107; for the asymmetric
desymmetrization of silacyclobutanes, see: c) R. Shintani, K.
Moriya, T. Hayashi, J. Am. Chem. Soc. 2011, 133, 16440; d) R.
Shintani, K. Moriya, T. Hayashi, Org. Lett. 2012, 14, 2902; for the
À
À
that the Si C to Si O transformation by ozone oxidation
proceeds predominantly with retention of configuration at the
silicon stereocenter. Thus, alkenylhydrosilanes 5 are versatile
chiral building blocks for a variety of functionalized non-
racemic silanes through stereoselective conversion of the
hydride and alkenyl moieties into alkyl or oxy functional
groups by Pt0-catalyzed hydrosilylation or ozone oxidation,
respectively.
In summary, we have developed a catalytic desymmetri-
zation of dihydrosilanes based on Pt0-catalyzed hydrosilyla-
tion with taddol-derived phosphonite ligands. This method
affords a multifunctionalized nonracemic alkenylhydrosilane,
which is a synthetically valuable sila-chiral building block.
Further studies toward expanding the present asymmetric
method to other functionalized silanes and investigation of
their applications are in progress.
À
desymmetric C H bond functionalization of achiral triarylsi-
lanes, see: e) R. Shintani, H. Otomo, K. Ota, T. Hayashi, J. Am.
Chem. Soc. 2012, 134, 7305; for the desymmetric transmetalation
of achiral triarylsilanes, see: f) R. Shintani, E. E. Maciver, F.
Tamakuni, T. Hayashi, J. Am. Chem. Soc. 2012, 134, 16955.
[8] Enantiomeric resolutions of racemic chiral silanes have been
reported. For methods mediated by microbial cells or isolated
enzymes, see: a) R. Tacke, K. Fritsche, A. Tafel, F. Wuttke, J.
Organomet. Chem. 1990, 388, 47; b) R. Tacke, S. Brakmann, F.
Wuttke, J. Organomet. Chem. 1991, 403, 29; c) N. E. Aouf, A. H.
Djerourou, L. Blanco, Phosphorus Sulfur Silicon Relat. Elem.
1994, 88, 207; d) T. Fukui, T. Kawamoto, A. Tanaka, Tetrahe-
dron: Asymmetry 1994, 5, 73; e) R. Tacke, T. Heinrich, Silicon
Chem. 2002, 1, 35; for resolution by HPLC using a chiral
stationary phase, see: f) R. Tacke, D. Reichel, K. Gꢂnther, S.
Merget, Z. Naturforsch. B 1995, 50, 568; g) A. Mori, F. Toriyama,
H. Kajiro, K. Hirabayashi, Y. Nishihara, T. Hiyama, Chem. Lett.
1999, 549; h) T. Schmid, J. O. Daiss, R. Ilg, H. Surburg, R. Tacke,
Organometallics 2003, 22, 4343.
Received: September 12, 2012
Published online: November 7, 2012
Keywords: asymmetric synthesis · enantioselectivity ·
hydrosilylation · ozone · silanes
.
[1] For selected reviews on nonracemic silanes possessing a silicon
stereocenter, see: a) L. H. Sommer, Stereochemistry, Mechanism
and Silicon, McGraw-Hill, New York, 1965; b) R. J. P. Corriu, C.
Guꢀrin, J. J. E. Moreau in Topics in Stereochemistry, Vol. 15
(Ed.: E. L. Eliel), Wiley, New York, 1984, pp. 43 – 198; c) M. A.
Brook in Silicon in Organic, Organometallic, and Polymer
Chemistry, Wiley, New York, 2000, pp. 115 – 137; d) T. Murafuji,
K. Kurotobi, N. Nakamura, Y. Sugihara, Curr. Org. Chem. 2002,
[9] For pioneering works on catalytic asymmetric reactions using
taddol-derived phosphonites, see: a) D. Seebach, M. Hayakawa,
J. Sakaki, W. B. Schweizer, Tetrahedron 1993, 49, 1711; b) J.
Sakaki, W. B. Schweizer, D. Seebach, Helv. Chim. Acta 1993, 76,
2654.
Angew. Chem. Int. Ed. 2012, 51, 12745 –12748
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 12747

.
Angewandte
Communications
[10] For a recent review on the taddol-derived phosphonite ligand,
see: H. W. Lam, Synthesis 2011, 2011.
related additions and corrections, see: H. E. Burks, L. T. Kliman,
J. P. Morken, J. Am. Chem. Soc. 2010, 132, 13949.
[15] For the results of a similar reaction using other monodentate and
bidentate chiral phosphorous ligands, see the Supporting Infor-
mation.
[16] The catalytic system of [Pt(dba)3] and phosphonite 6 in a 1:2
molar ratio afforded the highest enantioselectivities in our
attempts.
[11] Morken and co-workers developed an asymmetric diboration of
alkenes and 1,4-dienes using the taddol-derived phosphonite
ligand catalytic system; see: a) H. E. Burks, L. T. Kliman, J. P.
Morken, J. Am. Chem. Soc. 2009, 131, 9134; b) L. T. Kliman,
S. N. Mlynarski, J. P. Morken, J. Am. Chem. Soc. 2009, 131,
13210.
[12] Oestreich and colleagues reported the kinetic resolution of
[17] The absolute stereochemistry of 5ab and 5ac were determined
by a method similar to that described in Scheme 2 for 5aa, see
the Supporting Information for more information.
[18] The absolute stereochemistry of 5b and 5c has not yet been
determined. Attempts to derivatize these nonracemic alkenyl-
hydrosilanes into crystalline compounds or stereochemically
defined authentic samples are in progress.
[19] L. H. Sommer, J. E. Lyons, H. Fujimoto, J. Am. Chem. Soc. 1969,
91, 7051.
[20] A. G. Brook, K. H. Pannell, D. G. Anderson, J. Am. Chem. Soc.
1968, 90, 4374.
À
chiral alcohols by dehydrogenative Si O coupling using a Cu
catalyst with taddol-derived phosphonite ligands: A. Weickge-
nannt, M. Mewald, T. W. T. Muesmann, M. Oestreich, Angew.
Chem. 2010, 122, 2269; Angew. Chem. Int. Ed. 2010, 49, 2223.
[13] The hydrosilylation of dihydrosilane with alkynes in the
presence of an achiral catalyst has been reported; see: a) T.
Kusumoto, T. Hiyama, Chem. Lett. 1985, 1405; b) S. J. Lee, M. K.
Park, B. H. Han, Silicon Chem. 2002, 1, 41; c) T. Takahashi, F.
Bao, G. Gao, M. Ogasawara, Org. Lett. 2003, 5, 3479; d) A.
Corma, C. Gonzꢃlez-Arellano, M. Iglesias, F. Sꢃnchez, Angew.
Chem. 2007, 119, 7966; Angew. Chem. Int. Ed. 2007, 46, 7820;
e) J. Montenegro, J. Bergueiro, C. Saꢃ, S. Lꢄpez, Org. Lett. 2009,
11, 141; f) Y. Sumida, T. Kato, S. Yoshida, T. Hosoya, Org. Lett.
2012, 14, 1552.
[21] a) M. Murakami, K. Sakita, K. Igawa, K. Tomooka, Org. Lett.
2006, 8, 4023; b) K. Igawa, K. Sakita, M. Murakami, K.
Tomooka, Synthesis 2008, 1641; c) K. Igawa, Y. Kawasaki, K.
Tomooka, Chem. Lett. 2011, 40, 233.
[14] [Pt(dba)3] and phosphonite ligands 6a and 6c were prepared
according to the procedures of Morken et al.; see: Ref. [11]. For
12748 www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 12745 –12748