Silylative cyclopropanation of allyl phosphates with silylboronates

Article abstract of DOI:10.1002/anie.201403726

A potassium-bis(trimethylsilyl)amide-mediated cyclopropanation of allyl phosphates with silylboronates has been developed. Unlike the reported copper-catalyzed allylic substitution reactions, the nucleophile selectively attacks at the β-position of the allylic substrates under the present reaction conditions. The mechanism of this process has also been investigated, thus indicating the involvement of a silylpotassium species as the active nucleophilic component.

Full text of DOI:10.1002/anie.201403726

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Angewandte
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DOI: 10.1002/anie.201403726
Small Ring Systems
Silylative Cyclopropanation of Allyl Phosphates with Silylboronates**
Ryo Shintani,* Ryuhei Fujie, Momotaro Takeda, and Kyoko Nozaki*
Abstract:
A
potassium-bis(trimethylsilyl)amide-mediated
intermediates have been reported by using enolate-based
carbon nucleophiles for intermolecular reactions, as well as
nitrogen[5] and oxygen[6] nucleophiles for intramolecular
cyclization reactions, but the use of other heteroatom
nucleophiles has been scarcely explored. In fact, a copper-
catalyzed intermolecular borylative cyclopropanation[7] and
an intramolecular silylative cyclopropanation using elaborate
(allyloxy)silyllithiums generated in situ[8] have only been
reported as far as we are aware. In this context, we herein
describe the development of a potassium-bis(trimethylsilyl)-
amide-mediated carbon–silicon bond-forming cyclopropana-
tion of allyl phosphates with silylboronates, in the absence of
any transition-metal catalysts, to provide straightforward
access to silicon-containing cyclopropanes with high selectiv-
ity.
The reaction of allyl phosphates with silylboronates is
known to be promoted by copper catalysts in the presence of
a metal alkoxide or hydroxide base to give allylsilanes as the
product through an allylic substitution pathway.[9,10] During
the course of our study on the effect of a base on this copper
catalysis, we unexpectedly found that a silylative cyclopropa-
nation through nucleophilic attack at the b-position could
take place when no copper catalysts were employed. Thus,
a reaction of cinnamyl diethyl phosphate (1a) with 1.5 equiv-
alents of the silylboronate 2[11,12] in the presence of 5 mol% of
CuI and 1.5 equivalents of NaOtBu in THF at 08C gave only
allylic substitution products as a mixture of the g-substitution
product 3a (34% yield) and a-substitution product 4a (51%
yield) as shown in Equation (1) (THF = tetrahydrofuran).
cyclopropanation of allyl phosphates with silylboronates has
been developed. Unlike the reported copper-catalyzed allylic
substitution reactions, the nucleophile selectively attacks at the
b-position of the allylic substrates under the present reaction
conditions. The mechanism of this process has also been
investigated, thus indicating the involvement of a silylpotassium
species as the active nucleophilic component.
C
hanging the existing reaction patterns to unusual ones by
adding catalysts or reagents represents a powerful approach
to the development of new synthetic methods in organic
chemistry. In this regard, the nucleophilic attack on an allylic
electrophile at its b-position, rather than at the usual a- or g-
position, could lead to cyclopropanes instead of the allylic
substitution products (Scheme 1). Except for the use of
Scheme 1. Allylic substitution versus cyclopropanation in the nucleo-
philic attack to an allylic electrophile.
Michael acceptors (R = electron-withdrawing group in
Scheme 1),[1,2] which electronically facilitate the selective
attack of a nucleophile at the b-position, a limited number of
methods have been developed to date for cyclopropanation of
less electronically biased allylic electrophiles (e.g., R = aryl,
alkyl, H, etc.). For example, palladium-mediated[3] or palla-
dium-catalyzed[4] cyclopropanation through p-allylpalladium
[*] Dr. R. Shintani, R. Fujie, Prof. Dr. K. Nozaki
Department of Chemistry and Biotechnology
Graduate School of Engineering, The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
E-mail: shintani@chembio.t.u-tokyo.ac.jp
nozaki@chembio.t.u-tokyo.ac.jp
In contrast, when this reaction was conducted in the
absence of a copper catalyst under otherwise identical
conditions, the cyclopropane trans-5a was obtained as the
major product (51% yield) along with 4a (17% yield).[13]
Subsequently, we found that the use of KOtBu[14] instead of
NaOtBu improved the selectivity towards 5a (Table 1, entry 1
versus entry 2), and high selectivity of 5a was realized by
employing KN(SiMe3)2[15] (5a/4a = 99:1; entry 3). In compar-
ison, the use of the related NaN(SiMe3)2 or LiN(SiMe3)2
resulted in somewhat lower selectivity of 5a (entries 4 and
5). In addition, the use of a phosphate as the leaving group
Dr. M. Takeda
Department of Chemistry, Graduate School of Science
Kyoto University, Kyoto 606-8502 (Japan)
[**] Support has been provided in part by a Grant-in-Aid for Young
Scientists (B), the Ministry of Education, Culture, Sports, Science
and Technology (Japan), and the Asahi Glass Foundation. M.T.
thanks JSPS for a fellowship.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201403726.
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Table 1: Silylative cyclopropanation versus allylic substitution: Effect of
bases and leaving groups.
Table 2: Silylative cyclopropanation of the allyl phosphates 1 with
silylboronate 2: Scope.
Entry
1
Substrate
Base
Yield [%][a]
5a+4a
5a/4a[a]
Entry
R
5[a]
Yield [%][b]
5+4
5/4[c]
1a
NaOtBu
68
75:25
(X=OP(O)(OEt)2)
1a
1a
1a
1
2
3
5a
5b
5c
71
99:1
2
3
4
5
6
7
KOtBu
54
77
83
57
22
0
85:15
99:1
77:23
78:22
<1:99
–
KN(SiMe3)2
NaN(SiMe3)2
LiN(SiMe3)2
KN(SiMe3)2
KN(SiMe3)2
75
99:1
1a
68[d]
>99:1
6 (X=Cl)
7 (X=OCO2Et)
[a] Determined by 1H NMR spectroscopy.
4
5
5d
5e
75
79
99:1
77:23
was essential for the present silylative cyclopropanation. For
example, cinnamyl chloride (6) gave only 4a in 22% yield
(entry 6) and cinnamyl ethyl carbonate (7) did not give any
substitution or cyclopropanation products because of the
decomposition of 7 under these reaction conditions (entry 7).
Under the reaction conditions described in Table 1,
entry 3, several substituted phenyl groups are tolerated at
the g-position of allyl phosphates 1 for the reaction with 2 to
give the corresponding cyclopropanes 5 as the major product,
although the use of the electron-rich substrate 1e results in
somewhat lower selectivity (Table 2, entries 2–5). Substrates
with naphthyl, thienyl, pyridyl, or alkenyl groups can also be
employed with high selectivity toward the cyclopropanes 5,
albeit in a low yield for the pyridyl cyclopropane 5i because of
the partial decomposition of 1i during the reaction (5/4 ꢀ
92:8; entries 6–10).[16] In addition to these g-monosubstituted
allyl phosphates, the g,g-disubstituted allyl phosphate 1k is
a suitable substrate and provides the cyclopropane 5k
selectively over the allylsilane 4k in 83% combined yield as
shown in Equation (2).
6
7
5 f
73
84
96:4
96:4
5g
8
5h
5i
63
99:1
92:8
93:7
9[e]
10[g]
38[f]
71
5j[h]
[a] Obtained as a trans isomer unless otherwise noted. [b] Yield of
isolated product. [c] Determined by 1H NMR spectroscopy. [d] Calcu-
lated yield of 5c after silica gel chromatography (contained inseparable
PhMe2SiSiMe2Ph; 10% based on 2). [e] The reaction was conducted at
À208C for 4.5 h. [f] Yield of 5i+4i as determined by 1H NMR analysis
after silica gel chromatography. [g] The reaction was conducted at À208C
for 6 h. [h] 5j was obtained as a mixture of trans/cis=94:6.
Having established the potassium bis(trimethylsilyl)-
amide-mediated silylative cyclopropanation of allyl phos-
phates with a silylboronate, we turned our attention to
understanding how this reaction takes place. At first, we
confirmed that the silylation does occur at the b-position of
allyl phosphates by employing the a,a-bis(deuterated) sub-
strate [D2]-1a as illustrated in Equation (3). To gain insights
into the nature of the active nucleophilic component, we
monitored a [D8]THF solution of a 1:1 mixture of silylboro-
nate 2 and potassium bis(trimethylsilyl)amide by 11B NMR
spectroscopy at 08C [Eq. (4)]. As a result, two broad peaks at
d = 8.4 and 25.0 ppm were observed with the area ratio of
1:1.4. Based on the relevant literature precedents,[13b,c,17] these
peaks could be assigned as tetracoordinated anionic boron
species 8 and the desilylated three-coordinate boron species 9,
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Scheme 2. a) Proposed reaction pathway from 5 to 11 in Equation (6).
b) Overall skeletal rearrangement of Ca-Cb-Cc from 1 to 11.
respectively. The formation of 9 indicates the generation of
dimethylphenylsilylpotassium (10) as the byproduct,[18] which
could be the active nucleophile in the present cyclopropana-
tion. To probe its possibility, we separately prepared 10 by the
known procedure from the corresponding disilane and
metallic potassium[19] and reacted it with 1a [Eq. (5)].
found that a silylpotassium species could be the active
nucleophilic component.
Experimental Section
General procedure for reaction shown in Table 2: The silylboronate 2
(123 mL, 0.451 mmol) and THF (0.20 mL) were added to a solution of
KN(SiMe3)2 (89.8 mg, 0.450 mmol) in THF (1.00 mL) at 08C. The
compound 1 (0.300 mmol) was then added to the reaction mixture
with additional THF (0.30 mL), and the resulting mixture was stirred
for 3 h at 08C. After dilution with Et2O, the reaction mixture was
passed through a pad of silica gel with EtOAc, and the solvent was
removed under vacuum. The residue was purified by silica gel
preparative TLC with n-hexane/EtOAc to afford compound 5/4.
Under these reaction conditions, 5a was obtained in 62%
yield with no formation of 4a. These results suggest that 10 is
at least partially responsible as the active nucleophile in the
present cyclopropanation using 2 and potassium bis(trime-
thylsilyl)amide.[20]
With regard to the derivatization of these cyclopropanes,
we have found an unusual oxidation reactions using the
Tamao–Fleming conditions.[21–23] Thus, in our preliminary
experiment, the reaction of 5a under the reaction conditions
shown in Equation (6) preferentially produced the ring-
Received: March 26, 2014
Revised: April 19, 2014
Published online: May 13, 2014
Keywords: reaction mechanisms · rearrangement · silanes ·
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small ring system · synthetic methods
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thylsilyl)amide-mediated cyclopropanation of allyl phos-
phates with a silylboronate. Unlike the previously reported
copper-catalyzed allylic substitution reactions, the nucleo-
phile selectively attacks at the b-position of the allylic
substrates under the present reaction conditions. We have
also investigated the mechanistic aspect of this process and
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