Relay catalysis using a gold(i) complex/Bronsted acid binary system for the synthesis of bezoxasiloles

Article abstract of DOI:10.1039/c3ra47149g

A strategy for the synthesis of synthetically useful benzoxasilole derivatives by combining a gold(i) complex/Bronsted acid binary system and a temporary silicon tether method has been developed that involves relay catalytic cascade intramolecular allylation of alkynes by a gold(i) complex and addition of silanols to enones by a Bronsted acid.

Full text of DOI:10.1039/c3ra47149g

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Relay catalysis using a gold(I) complex/Brønsted
acid binary system for the synthesis of
bezoxasiloles†
Cite this: RSC Adv., 2014, 4, 6215
Received 29th November 2013
Accepted 17th December 2013
*
Yoshikazu Horino, Yu Takahashi, Yuichi Nakashima and Hitoshi Abe
DOI: 10.1039/c3ra47149g
www.rsc.org/advances
A strategy for the synthesis of synthetically useful benzoxasilole by a gold(I) complex produces skipped 1,4-dienes possessing
derivatives by combining a gold(I) complex/Brønsted acid binary silanol substituents.7 On the basis of recently developed relay
system and a temporary silicon tether method has been developed catalysis and our report, we envisioned that the silanol 2 might
that involves relay catalytic cascade intramolecular allylation of undergo intramolecular addition to enones to produce ben-
alkynes by a gold(I) complex and addition of silanols to enones by a zoxasilole derivatives in a single synthetic operation if a
Brønsted acid.
Brønsted acid or a Brønsted acid derived from a cationic
gold(I) complex and a water exists (Scheme 1).8 Herein, we
report a cationic gold(I) complex/Brønsted acid binary system
is the effective in the relay catalysis of a cascade reaction that
serves as an important alternative to the aldol reaction
between allyl phenyl ketone and ketones, and provides
access to b-carbonyl-substituted tertiary homoallylalcohol
derivatives.
We began our investigation by examining the cascade
intramolecular allylation of alkynes and the addition of
silanols to enones catalyzed by a cationic gold(I) complex/
Brønsted acid binary system. When the 1a was treated with
H2O (2 equiv) in the presence of 5 mol% of (Ph3P)AuNTf2 and
5 mol% TsOH in MeNO2 at room temperature, desired
The use of temporary silicon tethers in metal-mediated
organic reactions is widely accepted as an efficient method in
an intramolecular fashion for the structural elaboration of
complexity and diversity.1 Usually, products obtained using
the temporary silicon tether method give the opportunities to
convert into a number of other functional groups or mediate
further coupling reactions. Remarkable progress in this area
was made by Leighton and co-workers,2 who succeeded in
developing of highly enantioselective and regioselective ally-
lation of unsymmetrical b-diketones to produce b-carbonyl-
substituted tertiary homoallylalcohols that are not easily
accessed via the aldol reaction.3 Although tertiary b-hydroxy
ketones are well recognized as an important class of
compounds, only a few achievements and contributions have
been reported that involve transition metal-catalyzed an aldol
surrogate reaction.4 On the other hand, Gong and co-workers
reported cascade intramolecular hydrosilylation with alkynes
and the Mukaiyama aldol reaction catalyzed by a gold(I)
complex/Brønsted acid binary system.5 This reaction system
that complements the advantages of gold catalysis and orga-
nocatalysis exhibited the potential to enable unprecedented
transformations. Thus, the development of new methods for
accessing tertiary b-hydroxy ketones through the combined
use of a gold(I) complex and an organocatalyst appears to be a
powerful approach.6 Recently, we have reported that the
intramolecular allylation of alkynes with allylsilanes catalyzed
Department of Environmental Applied Chemistry, Faculty of Engineering, University of
Toyama, Gofuku 3190, Toyama 930-8555, Japan
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c3ra47149g
Scheme
synthesis of bezoxasiloles.
1 Gold(I) complex/Brønsted acid binary system for the
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Table 1 Optimization of reaction conditionsa
Table 2 Gold-catalyzed synthesis of aldol surrogates 3a
Entry
1
R
Time (h)
3
Yield (%)
Entry
L
X
Solvent
Time (h)
3a (%)
4 (%)
1
2
3
4
5
6
7
8
1b
1c
1d
1e
1f
1g
1h
1i
Et
Bn
i-Pr
CH(Me)Ph
c-Hex
1
1
1
1
1
2
2
2
1
1
0.5
3
3b
3c
3d
3e
3f
3g
3h
3i
76
73
85
75b
84
86
80
68
65
65
71
50
1b
2
3
4
5
6
7
8
9
PPh3
PPh3
PPh3
PPh3
PPh3
P(t-Bu)3
IPr
PPh3
PPh3
PPh3
NTf2
NTf2
NTf2
NTf2
NTf2
NTf2
NTf2
OTf
MeNO2
MeNO2
THF
dioxane
MeCN
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
2
1
14
14
14
3
3
1
2
24
84
78
6
33
0
71
11
62
73
0
0
0
19
33
0
t-Bu
4
CMe2CH ¼ CH2
48
13
14
0
Ph
9
1j
1k
1l
2-BrC6H4
4-BrC6H4
4-CH3CO2C6H4
4-MeOC6H4
3j
3k
3l
SbF6
BF4
10
11
12
10
1m
3m
a
Unless otherwise noted, the reaction was performed with 1a
b
a
(0.2 mmol), H2O (0.4 mmol) and solvent (1 mL). The reaction was
performed at room temperature in the presence of TsOH (5 mol%).
Unless otherwise noted, the reaction was performed with 1 (0.2 mmol),
H2O (0.4 mmol) and MeNO2 (1 mL). b Mixture of diastereomers (dr 1 : 1.4).
product 3a was obtained in high yield (Table 1, entry 1). We
are pleased to nd that even in the absence of the orthogonal
Brønsted acid, the both allylation of alkyne and addition of
the silanol to the enone proceeded in a single operation at
60 ꢀC, furnishing 3a in high yield (entry 2). Moreover, the
present reaction proceeded dependently on the solvent.9 For
example, when the reaction was performed in THF or
dioxane, 3a was obtained in low yields along with the
signicant amount of 4 (entries 3 and 4).10 The stereochem-
istry of 4 was determined to be Z by NOE experiment.
Meanwhile, the use of MeCN as the solvent resulted in no
reaction (entry 5). Among the several ligands tested, triphe-
nylphosphine showed the best catalytic activity (entries 2, 6,
and 7). In addition, although the use of AgSbF6 or AgOTf as
the silver additive provided 3a in satisfactory yields, but 4 was
also obtained (entries 8 and 9). On the other hand, changing
the silver additive from AgNTf2 to AgBF4 resulted in no
reaction (entry 10). Under the optimized reaction condition
in hand, the substrate scope for the relay catalytic cascade
intramolecular allylation with alkynes and addition of sila-
nols to enones was examined. The results presented in Table
2 demonstrated that the present reaction is general for a
variety of substituents of 1, which provides opportunities for
further elaboration of the surrogates for the aldol reaction. It
should be emphasized here that the use of 1b–1f gave the
desired products 3b–3f, respectively, which are considered to
be alternatives to asymmetric ketone–ketone aldol products
substitutions on the aryl moiety are also tolerated, but the
use of aryl ynone substrates 1i–1m slightly diminished yields
(entries 8–12).
Interestingly, when the 3-nitoropheny substituted ynone 1n
was subjected to 5 mol% (t-Bu3P)AuCl, 5 mol% AgNTf2, and 2.0
equivalents of H2O, benzoxasilole derivative 3n and spi-
rodihydoropyran derivatives 5a were obtained respectively (eqn
(1)). Furthermore, the reaction of 9-anthracenyl substituted
substrate 1o produced selectively 5b in good yield. In all cases,
spirodihydoropyran derivatives 5a and 5b were obtained as a
single diastereomer respectively.
(1)
Next, a crossover experiment was performed under the
(entries 1–4). Furthermore, allyl substituted 1h, possessing standard conditions using a 1 : 1 mixture of 1p and 1q (eqn (2)).
the 1,5-enyne skeleton, resulted in selective formation of No crossover products were detected at all by 1HNMR, whereas
desired benzoxasilole derivatives 3h over competing 1,5- the concerted products 3o and 3p were obtained in 70% and
enyne cycloisomerization (entry 7).11 In addition, 85% isolated yields, respectively, without any detectable
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scrambling. This result strongly suggests that the present
reaction proceeds intramoleculary.
On the other hand, the use of (S)-DTBM-SEGPHOS(AuCl)2
activated by AgNTf2 produced 3i in 6% ee. Unfortunately, the
combination of (S)-DTBM-SEGPHOS(AuMe)2 and chiral phos-
phoric acid 8 did not show catalytic activity. These results
suggest that the Brønsted acid is generated from a counter
anion of the gold(I) complex and water that dominates the
activation of the ketone enabling the addition of the silanol to
the enone in the second step. Although the enantioselectivity
must be improved, to the best of our knowledge, this is the rst
example to show that the Brønsted acid catalyzed enantiose-
lective addition of a silanol to an enone.
(2)
The benzoxasilole derivatives are known to serve as useful
reagents in a number of transformations such as Hiyama
coupling.12 Therefore, to evaluate the utility of the benzoxasilole
derivatives produced in this study, 3b, 3d and 3f were directly
subjected to simple deprotection conditions to remove the silyl
groups, providing corresponding b-carbonyl-substituted tertiary
homoallylalcohols 10a–10c in high yields (eqn (4)).
Several experiments were then conducted in order to gain
further insight into the reaction mechanism. First, we examined
the possibility that the reaction in the second step (the addition
step of the silanol to the enone) proceeds via a gold(I) complex
was explored. It was found that the Brønsted acid-catalysed
addition of a silanol to an enone proceeded much rapidly than
the reaction using the gold(I) complex when the alternative
substrate 6 was treated with the Tf2NH and the (Ph3P)AuCl/
AgNTf2 respectively (eqn (3)). Second, the gold(I) complex 8
incorporating binaphthol-derived phosphate anion as a chiral
counterion and (S)-DTBM-SEGPHOS(AuCl)2 as a chiral phos-
phine-substituted gold catalyst were used for the cascade reac-
tion of 1i to determine how the Brønsted acid is generated. The
reaction of 1i with the gold(I) complex 9 prepared by chiral
phosphoric acid 8 and (Ph3P)AuMe gave 3i in 28% ee (Scheme 2).
(4)
Furthermore, the benzoxasilole derivatives 3 are considered
to be silyl-protected aldol products. For example, the tert-bish-
omoallyl alcohol 12 was obtained from 3a in two steps via a
Wittig reaction condition followed by Tamao–Fleming oxida-
tion (eqn (5)).13 This type of bishomoallyl alcohols is a great deal
in organic synthesis.14
(3)
(5)
Conclusions
In conclusion, we have demonstrated a new strategy for the
synthesis of benzoxasilole derivatives by combining a temporary
silicon tether method and a relay catalysis using a gold(I)
complex/Brønsted acid binary system. The strategy involves a
cascade intramolecular allylation of alkynes and addition of
silanols to enones. The obtained products can be transformed
into synthetically valuable tertiary homoallylalcohols, including
ketone–ketone aldol products. Moreover, the present relay
catalysis would certainly suggested that the counter anions of
cationic metal complex has a potential to become not only
Brønsted acids but also chiral Brønsted acids. The development
of an enantioselective reaction is currently in progress.
Scheme 2 Comparison of chiral counterion versus chiral ligand for
asymmetric synthesis of benzoxasilole derivative 3i.
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