Regioselective silylzincation of phenylallene derivatives

Article abstract of DOI:10.1002/asia.200900452

This paper deals with our new approach for regio-controlled synthesis of exo/endo-vinylsilanes through silylzincation as a key reaction, using newly developed silylzinc reagents. In this system, by choosing appropriate zinc reagents, either exo-vinylsilane or endo-vinylsilane can be synthesized with good regioselectivity, using the same phenylallene substrates. (Chemical equation presented).

Full text of DOI:10.1002/asia.200900452

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DOI: 10.1002/asia.200900452
Regioselective Silylzincation of Phenylallene Derivatives
Mitsuhiro Yonehara,[a, b] Shinji Nakamura,[b] Atsuya Muranaka,[a] and
Masanobu Uchiyama*[a, b]
Dedicated to the 150th anniversary of Japan–UK diplomatic relations
Allyl- and vinylsilanes are important organometallics in
synthetic organic chemistry, because of their unique stability,
reactivity, and functional group tolerance, which make them
synthetically attractive.[1] Intermolecular silylmetalation of
alkynes, dienes, allenes, and alkenes[1d,2] constitutes an excel-
lent method for construction of the above compounds. How-
ever, controlling the regioselectivity in the silylmetalation of
The silylcupration of allenes by using higher/lower-order
cuprates has been extensively investigated,[3] whereas silyl-
zincation remains relatively unexplored.[4] We have recently
reported that a bulky zincate having one dimethylphenylsilyl
(DMPS) group (DMPS)ZntBu(OR)2ACHTUNTRGNE(NUG MM’) (1) ((OR)2 =
2,2’-biphenoxo, M=Li or MgCl, M’=MgCl, abbreviated as
SiBNOL-Zn-ate) can promote chemo- and regioselective si-
lylzincation of terminal alkynes to give branched vinylsi-
lanes regioselectively.[5] However, simple application of this
protocol to allenes using 1 proved unsuccessful because of
the low regioselectivity. Our initial studies using phenylal-
lene (2a) as a model substrate, aimed at identifying more fa-
vorable reaction conditions, revealed that a dimethylphenyl-
silyl (DMPS) group as the silyl moiety and THF as the sol-
vent were suitable starting points for optimization of the si-
lylzincation reaction conditions. The silylzincation reactions
of 2a with the use of DMPS-Li or DMPS-Zn-Cl were unsat-
isfactory in terms of reactivity (yield) and selectivity; in-
stead, undesired reactions occurred (Table 1, Entry 8 and
Supporting Information). However, when a mixture of
À
unsaturated C C bonds remains an important challenge.
Unsymmetrically substituted allenes are regarded as among
the most challenging, because the intermolecular silylmeta-
lation reaction can generate four isomers (exo/endo-vinyl/al-
lylsilane) (Figure 1). Herein, we describe our new approach
for the preparation of regio-controlled exo/endo-vinylsilanes
through silylzincation as a key reaction, using newly devel-
oped silylzinc reagents. We also describe the dramatic ef-
fects of the number and the nature of the ligands on Zn
upon the direction of the silylzincation reaction.
Table 1. Screening of zinc reagents for highly regio-selective silylzinca-
tion of phenylallene (2a).[a]
Figure 1. Reaction patterns in silylmetalation of unsymmetrical allenes.
Entry
Si-Zn Reagent
Yield[b] [%]
Selectivity
3a/4a
[a] M. Yonehara, Dr. A. Muranaka, Prof. Dr. M. Uchiyama
Advanced Elements Chemistry Laboratory
Advanced Science Institute, RIKEN
1
2
3
4
5
6
7
8
N
83
90:10
88:12
89:11
41:59
30:70
8:92
84[c]
76
85[c]
90
2-1 Hirosawa, Wako-shi, Saitama 351-0198 (Japan)
Fax : (+81)48-467-2879
E-mail: uchi_yama@riken.jp
93[c]
50
31:69
–
[b] M. Yonehara, Dr. S. Nakamura, Prof. Dr. M. Uchiyama
Graduate School of Pharmaceutical Sciences
The University of Tokyo
trace
[a] Unless otherwise noted, the silylzincation reaction was carried out
using silylzinc reagent (1.1 equiv) and phenylallene (2a) (1.0 equiv) in
THF at room temperature for 1 h. [b] Yield of isolated vinylsilanes.
[c] The reaction was carried out for 24 h.
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.200900452.
452
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Chem. Asian J. 2010, 5, 452 – 455

Table 2. Silylation of various phenylallene derivatives with (PhMe2Si)ZnMe and (PhMe2Si)3ZnLi.[a]
newly designed heteroleptic si-
lylzinc reagent, DMPS-Zn-R
(R=Me or tBu), prepared in
situ from ZnCl2, RMgCl and
DMPS-Li, and 2a (1.1:1.0
molar ratio) in THF, was stirred
at room temperature for 1 h,
the silylzincation proceeded
smoothly without any catalyst
to give predominantly exo-vi-
nylsilane (3a), and formation of
allylsilane was undetectable
(Entries 1 and 3). Extension of
the reaction time to 24 h gave
almost the same results (e.g.,
Entries 1 and 2). Attempts to
use homoleptic-type disilylzinc
reagents, such as (DMPS)2Zn,
proved unsuccessful in terms of
the selectivity (Entry 4). On the
Entry
Substrate
Si-Zn Reagent
t [h]
T [8C]
Yield[b] [%]
Selectivity
3:4
1
2
U
1
24
RT
RT
69
89
83:17
1:99
3
4
N
1
24
RT
RT
57
89
94:6
12:88
5
6
N
24
24
À78
44
72
98:2
16:84
RT
7
8
N
24
24
À78
71
90
94:6
16:84
RT
97:3
9
10
N
24
24
À78
57
RT
<26[c]
12:88
11
12
U
1
24
À100
À78
55
72
64:36
15:85
13
14
U
1
24
À78
À40
44
75
89:11
28:72
other
hand,
trisilylzincate,
(DMPS)3ZnLi turned out to
promote the silylzincation reac-
tion of 2a in good yield at
room temperature for 1 hour,
and endo-vinylsilane (4a) was
obtained as the major product,
in contrast with the case of het-
eroleptic-type DMPS-Zn-R re-
agent. The endo selectivity in-
creased with the prolongation
of the reaction time when
(DMPS)3ZnLi was used. Sever-
al attempts to use dianion-type
15
16
N
1
24
RT
RT
58
100
90:10
1:99
17
18
N
1
24
RT
RT
76
92
95:5
10:90
19
20
N
6
24
À78
46
78
93:7
19:81
RT
[a] Unless otherwise noted, the silylzincation reaction was carried out using silylzinc reagent (1.1 equiv) and
substrate (1.0 equiv) in THF under the given conditions. [b] Yield of isolated vinylsilanes. [c] Several minor
products that were difficult to separate were observed, resulting from halogen–metal exchange reaction.
silylzincates,
including
(DMPS)4ZnLi2 and 1, proved unsuccessful at this early
stage. The steric bulkiness of the silyl group in the zinc re-
agent had little effect on the exo/endo selectivity (Support-
ing Information).
vinylsilane 3a generated by the silylmetalation of 2a with
DMPS-Zn-R could be transformed into cross-coupling and
ketone products (Scheme 1).
Finally, a theoretical/computational study was performed
to understand the present silylzincation.[8] The experimental
results strongly indicate that exo-selective silylmetalation
with DMPS-Zn-R is controlled kinetically, whereas endo-se-
lective silylmetalation is subject to thermodynamic control.
With optimized conditions for the regio-controlled synthe-
sis of exo/endo-vinylsilane in hand, we studied the scope of
this new protocol,[6] and representative results are summar-
ized in Table 2. A variety of functional groups, including
alkyl, halogen, carbonyl, and alkoxy on a benzene ring, and
various aryl groups could be utilized in the reaction. In this
system, by choosing appropriate zinc reagents and reaction
conditions for the silylzincation, either exo-vinylsilane or
endo-vinylsilane could be obtained with good regioselectivi-
ty, using the same phenylallene substrate. To our knowledge,
the reaction with the use of heteroleptic-type DMPS-Zn-R
reagent is the first example of an efficient exo-selective silyl-
metalation with wide substrate generality. On the other
hand, endo-selective silylmetalations of unsymmetrical al-
lenes under thermodynamic conditions have been reported
in some cases with silylcuprates.[2c]
DFT/MP2
calculations
(MP2/6311SVP//B3LYP/
631SVPs)[9,10] were carried out to investigate the reaction
pathway of the silylzincation of 2a with DMPS-Zn-R. We
The potential to generate functionalized exo/endo-vinylsi-
lanes was next examined.[5c,7] We verified that the resultant
Scheme 1. Transformation of the resultant vinylsilane 3a.
Chem. Asian J. 2010, 5, 452 – 455
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453

M. Uchiyama et al.
COMMUNICATION
and we could identify CPexo and
CPendo as the global minima for
exo- and endo-adducts, respec-
tively (Figure 4). While it is dif-
ficult to provide hard theoreti-
cal evidence in support of an
energy difference of only sever-
al kcalmolÀ1 between the CPs,
CPendo is more stable by 2.6 kcal
molÀ1 than CPexo, which is in
good agreement with the exper-
imental observations.
Figure 2. Reactants, TSs, and complexes in the silylmetalation reaction of (Me3Si)ZnMe with 2a. Bond lengths,
angles, and energy changes at the MP2/6311SVP//B3LYP/631SVPs level are shown in ꢂ, deg, and kcalmolÀ1
respectively.
,
employed (Me3Si)ZnMe as a chemical model for DMPS-Zn-
R. Although it is important to keep in mind the possibility
that the simplification of the silyl moiety of this model may
lead to underestimation of the steric interactions, this struc-
ture provides a valuable starting point for consideration of
the reactivity of DMPS-Zn-R. The reaction pathway of the
silylzincation of 2a using (Me3Si)ZnMe is shown in Figure 2.
In both routes, we could not find any energetically plausible
initial complex, and it appears that the silylmetalation takes
place directly from the reactants (SM) via the distorted “tri-
angular transition state (TS)” with relatively low activation
energy. The TS for the exo-silylzincation is more stable by
approximately 3 kcalmolÀ1 than that for endo-one, which is
in good agreement with the experimental selectivity.
Orbital analysis lends some support to this regioselectivi-
Figure 4. Comparison of thermal stability of the possible vinylsilane inter-
mediates. Bond lengths, angles, and energy changes at the MP2/
6311SVP//B3LYP/631SVPs level are shown in ꢂ, deg, and kcalmolÀ1, re-
spectively. (S=Me2O).
ty. The localized Kohn–Sham (HOMO) orbital of 2a is lo-
calized on the double bond adjacent to the benzene moiety
because of their conjugation (Figure 3), and hence the
In conclusion, regioselective silylzincation of functional-
ized phenylallenes and versatile generation of vinylsilanes
could be achieved by utilizing the drastic ligand effects
found in zinc reagents. The present work underlines the util-
ity of adjusting the nature and number of ligands of zinc re-
agents as a means of tuning functionality in the develop-
ment of new reactions. Efforts to expand the reaction scope
and to elucidate the reaction pathway with the help of theo-
retical and spectroscopic studies are in progress in our labo-
ratory.
Figure 3. The Kohn–Sham MO of 2a.
double bond reacts with the vacant orbital of the zinc of 2a
preferentially over the other outside one. Among several
possible TSs for the silylzincation of 2a using (Me3Si)ZnMe
to afford exo/endo-allysilanes, we could identify one of each,
which are much less stable than the TSs for vinylsilane for-
mation by more than 10 kcalmolÀ1 (Supporting Informa-
tion).
It is experimentally observed that the regioselectivity in
the silylzincation of phenylallenes with (DMPS)3ZnLi is
thermodynamically controlled, giving predominantly endo-
vinylsilanes as the reaction time is extended. To examine the
regioselectivity in question, we examined each plausible in-
termediate generated by the silylzincation of 2a with a silyl-
zincate. (Me3Si)3ZnLi was used as a model of (DMPS)3ZnLi.
Several local minimum structures of each were optimized
Experimental Section
Typical procedure for the silylzincation reaction of 2a (Table 1, Entry 1):
To a stirred solution of (PhMe2Si)ZnMe (1.1 mmol) in THF, 1-phenylal-
lene (116 mg, 1.0 mmol) was added with a syringe at À788C. The mixture
was stirred at room temperature for 1 h, then was quenched with a satu-
rated aqueous solution of NH4Cl at 08C, and was extracted with Et2O
(2ꢁ30 mL). The organic solution was washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo. Purification of the residue
by silica gel column chromatography (n-hexane), furnished a mixture of
2-(dimethylphenylsilyl)-3-phenyl-1-propene (3a) and 2-(dimethylphenyl-
silyl)-3-phenyl-2-propene (4a) as a colorless oil (209 mg, 83%). The ratio
of products was determined from the 1H NMR (3a/4a=90:10). 1H NMR
454
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Chem. Asian J. 2010, 5, 452 – 455

Regioselective Silylzincation of Phenylallene Derivatives
(300 MHz, CDCl3, TMS) (3a): d=7.49–7.44 (2H, m), 7.38–7.29 (3H, m),
7.24–7.12 (3H, m), 7.05 (2H, d, J=7.5 Hz), 5.55 (1H, s), 5.49 (1H, s),
3.42 (2H, s), 0.25 ppm (6H, s); 1H NMR (4a): d=7.58–7.54 (2H, m),
7.43–7.15 (8H, m), 6.80 (1H, s), 1.94 (3H, s), 0.44 ppm (6H, s); HRMS
(EI): m/z (%) calcd for C17H20Si: 252.1334 [M+]; found: 252.1324. For
preparative procedures and spectroscopic data, see the Supporting Infor-
mation.
[4] Transition metal-catalyzed silylzincation of allenes was reported, but
the regioselectivity was not satisfactory: Y. Morizawa, H. Oda, K.
Oshima, H. Nozaki, Tetrahedron Lett. 1984, 25, 1163.
[5] a) S. Nakamura, M. Uchiyama, T. Ohwada, J. Am. Chem. Soc. 2004,
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Soc. 2005, 127, 13116; c) S. Nakamura, M. Uchiyama, J. Am. Chem.
Soc. 2007, 129, 28.
[6] Allenes were synthesized according to the literature procedure, see:
a) M. S. Baird, A. V. Nizovtsev, I. G. Bolesov, Tetrahedron 2002, 58,
1581; b) J. Clayden, D. W. Watson, M. Chambers, Tetrahedron 2005,
61, 3195; c) T. Furuyama, M. Yonehara, S. Arimoto, M. Kobayashi,
Y. Matsumoto, M. Uchiyama, Chem. Eur. J. 2008, 14, 10348.
[7] a) Y. Hatanaka, T. Hiyama, J. Org. Chem. 1989, 54, 268; b) T.
Hiyama, Y. Hatanaka, Pure Appl. Chem. 1994, 66, 1471; c) Y. Hata-
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d) M. E. Jung, G. Piizi, J. Org. Chem. 2002, 67, 3911.
[8] All calculations were carried out with a Gaussian 03 program pack-
age. Gaussian 03 (revision E.01), M. J. Frisch, G. W. Trucks, H. B.
Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Mont-
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Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani,
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O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y.
Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg,
V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O.
Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Fores-
man, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski,
B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L.
Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Na-
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Acknowledgements
We gratefully acknowledge financial support from Hoansha, the Naito
foundation, Mochida memorial foundation, and KAKENHI (Young Sci-
entist (A), Houga, and Priority Area No. 459) (to M.U.). This work was
also supported by the Junior Research Associate Program in RIKEN
(The Institute of Physical and Chemical Research), Japan (to M.Y.). The
calculations were partially performed on the RIKEN Super Combined
Cluster (RSCC).
Keywords: allenes · metalation · regioselectivity · silanes ·
zinc
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Received: September 13, 2009
Published online: January 21, 2010
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