Synthesis of optically active tertiary silanes via Pd-catalyzed enantioselective arylation of secondary silanes

Article abstract of DOI:10.1039/c2cc36238d

We herein describe the development of an efficient enantioselective catalytic system that promotes the arylation of secondary silanes. Our method involves treatment of secondary silanes and aryl iodides with a Pd ₂(dba)₃-asymmetric p

Full text of DOI:10.1039/c2cc36238d

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COMMUNICATION
Synthesis of optically active tertiary silanes via Pd-catalyzed
enantioselective arylation of secondary silanesw
Yu Kurihara, Michihiro Nishikawa, Yoshinori Yamanoi* and Hiroshi Nishihara*
Received 28th August 2012, Accepted 16th October 2012
DOI: 10.1039/c2cc36238d
We herein describe the development of an efficient enantioselective
catalytic system that promotes the arylation of secondary silanes. Our
method involves treatment of secondary silanes and aryl iodides with
a Pd2(dba)3–asymmetric phosphoramidite ligand system to afford
optically active tertiary silanes with good enantioselectivities.
Optically active organosilicon compounds containing a stereo-
genic tetrahedral silicon atom are promising for use as chiral
auxiliaries, reagents, resolving agents, and drug candidates.1
Although considerable effort has been devoted to the preparation
of optically active silanes, most studies have centered on optical
resolution (Fig. 1a).2 The development of an asymmetric catalytic
process that yields stereogenic silanes is therefore expected to
enhance the potential of the synthetic tool. Many reports have
Fig. 1 Preparation of optically active tertiary silanes. (i) Optical resolution.
demonstrated transition metal-catalyzed Si–H functionalization as
a direct and effective method for the preparation of optically active
organosilicon compounds through carbenoid insertion,3 hydro-
silylation,4 reduction,5 and so on.6 However, most of them are
on the construction of the chirality on backbone carbon, and
there are a limited number of reports on the construction of
chiral silicon centers using a catalyst.7
(ii) Reduction with LiAlH4. (iii) Asymmetric transition metal catalyst.
((2-diphenylphosphino)-20-methoxy-1,10-biphenyl) did not demon-
strate reactivity and enantioselectivity (4%yield, 3%ee).11 In
contrast, TADDOL-based phosphoramidite (R,R)-1 afforded
products in high yield with moderate enantioselectivity
(Table 1, entry 1).12–15 Not only can TADDOL-based phos-
phoramidites be readily synthesized by published methods, but
such compounds also possess modular properties that allow
for fine-tuning of their steric and electronic characteristics.
The results of ligand modification are provided in Table 1. The
steric bulk of amine evidently has a significant impact on
enantioselectivity (entries 1–4). The effect of varying the aromatic
group of the TADDOL moiety was also subsequently examined
(entries 1 and 5–8). The electron-rich 3,5-diethylphenyl TADDOL-
based phosphoramidite (R,R)-6 ligand displayed the best
performance for this transformation. These results show that
the steric and electronic effects of the aromatic group on the
TADDOL moiety play a significant role in determining enantio-
selectivity. The low yield of this reaction is attributed to the
undesired reaction of the aryl iodide by the secondary silane. By
decreasing the reaction temperature, however, such decomposi-
tions or reductions could be suppressed and the enantioselectivity
slightly improved. The reaction did though require longer time to
reach completion at reduced temperature (entries 9 and 10).
Under the optimized reaction conditions, a wide range of
substrates was tested in order to determine the scope of this
reaction. As depicted in Table 2, Pd-catalyzed arylation of
secondary silanes proceeds in an enantioselective fashion.
Hydrosilanes are useful reducing agents in the presence of
transition metals. In particular, the reduction of aryl halides
with hydrosilanes has been widely investigated.8 We and other
groups have shown that hydrosilanes do not always act as reducing
agents; i.e. we demonstrated that aryl iodides induced arylation of
hydrosilanes with the aid of transition metal complexes.9,10 In the
present study, we describe the enantioselective arylation of prochiral
secondary silanes using an asymmetric Pd complex (Fig. 1b).
This versatile enantioselective arylation reaction of secondary
silanes is a valuable addition to existing methodologies for the
preparation of optically active tertiary silanes.
To tune product enantioselectivity through ligand design, we
first examined the reaction of methylphenylsilane and 2-iodo-
anisole in the presence of various phosphine ligands and
Pd2(dba)3 catalyst. Initially, axially asymmetric MeO–MOP
Department of Chemistry, School of Science, The University of
Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
E-mail: yamanoi@chem.s.u-tokyo.ac.jp,
nisihara@chem.s.u-tokyo.ac.jp; Fax: +81 3 5841 8063
w Electronic supplementary information (ESI) available: Compound
characterization data and copies of 1H and 13C NMR. CCDC 898062
((S)-19). For ESI and crystallographic data in CIF or other electronic
format. See DOI: 10.1039/c2cc36238d
c
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Table 2 Catalytic enantioselective arylation of secondary silanesa
Table 1 Optimization of the reaction conditionsa
Temp/
1C
Yield
Product (%)
Entry R1
R2 Ar
eeb,c (%)
1
2
3
4
5
6
Ph
Ph
Ph
Ph
Ph
Ph
Me 2-MeOC6H4 ꢀ40
Me 3-MeOC6H4 ꢀ40
Me 4-MeOC6H4 ꢀ40
Me 2-MeC6H6H4 ꢀ40
Me 2,3-Me2C6H4 ꢀ40
Me 2,4-Me2C6H4 ꢀ40
9
10
11
12
13
14
57
29
16
44
36
47
61 (+, S)d
23 (ꢀ)
Entry Ar
1
X
Temp/1C Time/d Yield (%) eeb (%)
8 (ꢀ)
58 (ꢀ, S)d
67(ꢀ)
20
20
20
2
2
2
92
43
53
36
21
20
53 (ꢀ)
2
3
7
Ph
Me
ꢀ40
15
29
77(ꢀ)
8
9
10
11
12
13
Ph
Ph
Ph
Me 1-Np
20
16
17
18
19
20
21
58
73
73
54
36
34
51 (ꢀ, S)d
70 (+)
76(+)
73 (+, S)
11(ND)e
28 (ꢀ)
nPr 2-MeOC6H4 ꢀ40
iPr 2-MeOC6H4 ꢀ40
1-Np Me 2-MeOC6H4 ꢀ40
1-Np Ph 2-MeOC6H4
tBu Me 2-MeOC6H4
20
20
4
5
20
20
2
2
14
53
4
a
Unless otherwise noted, all reactions were conducted at 0.5 M in THF
with 2.5 mol% of Pd2(dba)3 and 7.5 mol% of ligand (R,R)-6. b Determined
by HPLC analysis. c Signs in the parentheses are those of [a]D in CH2Cl2.
d
The absolute stereo configurations were determined by the compar-
ison of [a]D of enantiomer-rich (or enantiopure) tertiary silanes or via
51
e
chiral HPLC analysis. [a]D value was approximately 0.
quantities with low asymmetric yields (entries 12 and 13).
The absolute stereo configurations of several products were
determined by optical rotation or chiral HPLC analysis
(entries 1, 4 and 8).8,16,17
6
7
20
20
2
2
35
65
54
39
To further investigate the stereochemistry of this reaction,
the absolute configuration of 19 was confirmed by single-
crystal X-ray analysis following a couple of recrystallization
steps of enantiomer-rich 19.18 HPLC analysis determined the
optical purity after recrystallization to be >99%ee. As shown
in Fig. 2, the absolute configuration of 19 was assigned as the
(S) enantiomer. These results reveal that ortho-substituted aryl
iodides react with pro-(S) at the hydrogen of secondary silanes
when (R,R)-6 is used as the chiral source.
8
20
2
28
o1
9
10
(R,R)-6
(R,R)-6
0
ꢀ40
2
3
64
57
57
61
a
The reaction was carried out with methylphenylsilane (1.5 mmol),
2-iodoanisole (1.0 mmol), triethylamine (3.0 mmol), Pd2(dba)3
b
(0.025 mmol), and L* (0.075 mmol) in THF (2.0 mL). Determined
by chiral HPLC analysis employing a chiral stationary phase.
These results indicate that the substitution pattern of the
substituent on the phenyl ring of aryl iodides has a major
effect on the enantioselectivity. Low asymmetric yields were
achieved with m- and p-substituted aryl iodides (entries 2 and
3). However, alkylarylsilanes with o-substituted aryl iodides
afforded useful chemical and asymmetric yields (entries 4–11).
In contrast, the corresponding monoarylated products of diaryl-
silane and dialkylsilane could only be synthesized in moderate
Fig. 2 X-ray structure analysis of enantiopure (S)-19. Purity >99%ee.
Chem. Commun., 2012, 48, 11564–11566 11565
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On the basis of the obtained results, a tentative transition state,
dominated by a repulsion among the ethyl group of (R,R)-6, the
o-substituent of the aryl iodide, and the alkyl group of the
secondary silane, was proposed.7 The reduced enantioselectivities
of m- and p-substituted aryl iodides as compared with the
o-substituted one can be attributed to the lack of steric effects
with the phosphoramidite ligand and secondary silanes.
In conclusion, we have described the first enantioselective
arylation of secondary silanes. TADDOL-based phosphora-
midite (R,R)-6 was found to be highly effective for palladium-
catalyzed asymmetric arylation of secondary silanes (up to
77%ee). Investigations evaluating the full scope of this reaction
are currently in progress.
7 For examples of enantioselective reaction of prochiral secondary
silanes, see: (a) Y. Yasutomi, H. Suematsu and T. Katsuki, J. Am.
Chem. Soc., 2010, 132, 4510; (b) D. R. Schmidt, S. J. O’Malley and
J. L. Leighton, J. Am. Chem. Soc., 2003, 125, 1190; (c) R. J. P.
Corriu and J. J. E. Moreau, J. Organomet. Chem., 1976, 120,
337.
8 (a) A. Kunai, T. Sakurai, E. Toyoda, M. Ishikawa and Y. Yamamoto,
Organometallics, 1994, 13, 3233; (b) R. Boukherroub, C. Chatgilialoglu
and G. Manuel, Organometallics, 1996, 15, 1508; (c) A. Iwata,
Y. Toyoshima, T. Hayashida, T. Ochi, A. Kunai and J. Ohshita,
J. Organomet. Chem., 2003, 667, 90; (d) A. Kunai and J. Ohshita,
J. Organomet. Chem., 2003, 686, 3; (e) J. Ohshita, R. Taketsugu,
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H. Nishihara, Tetrahedron Lett., 2006, 47, 7157; (c) Y. Yamanoi and
H. Nishihara, J. Org. Chem., 2008, 73, 6671; (d) Y. Yamanoi,
T. Taira, J.-I. Sato, I. Nakamula and H. Nishihara, Org. Lett.,
2007, 9, 4543; (e) Y. Yamanoi and H. Nishihara, J. Synth. Org.
Chem., Jpn., 2009, 67, 778; (f) Y. Yabusaki, N. Ohshima, H. Kondo,
T. Kusamoto, Y. Yamanoi and H. Nishihara, Chem.–Eur. J., 2010,
16, 5581; (g) A. Lesbani, H. Kondo, J.-I. Sato, Y. Yamanoi and
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H. Kondo, Y. Yabusaki, M. Nakai, Y. Yamanoi and H. Nishihara,
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10 For other examples of metal-catalyzed arylation of hydrosilanes,
see: (a) M. Murata and Y. Masuda, J. Synth. Org. Chem., Jpn.,
2010, 68, 845; (b) C. Huang, N. Chernyak, A. S. Dudnik and
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11 Although we tested (S)-(3,5-dioxa-4-phosphacyclohepta[2,1-a;3,4-a0]-
dinaphthalene-4-yl)bis[(1R)-1-phenylethyl]amine ((S,R,R)-22) and
(11aR)-10,11,12,13-tetrahydrodiindeno[7,1-de:1070-fg][1,3,2]dioxa-
phosphocin-5-bis[(R)-1-phenylethyl]amine (R,R,R)-23 as chiral
sources (purchased from STREM), the arylated product was
obtained in 25% yield, 2%ee and in 43% yield, 4%ee, respectively.
For the structures of (S,R,R)-22 and (R,R,R)-23, see ESIw.
12 For recent reviews highlighting the use of TADDOL-derived phos-
phoramide ligands in asymmetric synthesis, see: (a) H. W. Lam,
Synthesis, 2011, 2011; (b) H. Pellissier, Tetrahedron, 2008, 64, 10279.
13 For the absolute configuration of 1, see: N. Oka, M. Nakamura,
N. Soeda and T. Wada, J. Organomet. Chem., 2009, 694, 2171.
14 For reviews on monoligated Pd species in cross-coupling reactions,
see: (a) U. Christmann and R. Vilar, Angew. Chem., Int. Ed., 2005,
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15 The effect of varying the ratio of Pd source to ligand (R,R)-1 was
investigated. The results are summarized as follows: Pd: (R,R)-1 =
1 : 1 71% yield, 36%ee, Pd: (R,R)-1 = 1 : 1.5 92% yield, 36%ee,
and Pd: (R,R)-1 = 1 : 2 85% yield, 36%ee. The optimized ratio of
Pd: (R,R)-1 was determined to be 1 : 1.5. We therefore used this
ratio for all subsequent reactions.
We thank Ms Kimiyo Saeki and Dr Aiko Sakamoto, the
Elemental Analysis Center of The University of Tokyo, for
the elemental analysis measurements. The present work was
financially supported by Grant-in-Aids for Scientific Research
(C) (No. 24550221) and Scientific Research on Innovative
Areas ‘‘Coordination Programming’’ (area 2107, No. 21108002)
from the Ministry of Education, Culture, Sports, Science, and
Technology, Japan.
Notes and references
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c
11566 Chem. Commun., 2012, 48, 11564–11566
This journal is The Royal Society of Chemistry 2012