Studies on the 1,2-brook rearrangement of bissilyl ketones

Article abstract of DOI:10.1055/s-0028-1087535

The first 1,2-Brook rearrangements with bis(dimethylphenylsilyl) ketone, initiated after addition of different C- and S-nucleophiles, are described. The resulting, newly formed carbanion can be trapped with electrophiles thus paving the way for utilizing bissilyl ketones as formyl dianion equivalents in the future. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087535

LETTER
429
Studies on the 1,2-Brook Rearrangement of Bissilyl Ketones
1
, 2-Brook
Rearran
n
gment of Bis
d
silyl
K
etone
r
s
eas Kirschning,*a Silke Luiken,a Antonella Migliorini,a,b Maria Antonietta Loreto,b Monika Vogta
a
Institut für Organische Chemie, Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany
E-mail: andreas.kirschning@oci.uni-hannover.de
Dipartimento di Chimica, ‘Sapienza’ Università di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy
b
Received 2 October 2008
silyl) ketone 7.5a All these ketones show unusual
spectroscopic properties which are already evident from
their bright pink color.5,6 For example, the carbon atom of
7 shows an extreme paramagnetic signal shift (d = 318
ppm). These data and density functional calculations
(B3LYP, 6-31 G*) of bis(trimethylsilyl) ketone suggest
that the energy difference (HOMO/LUMO) for the n,p*
electron transfer (lmax = 513 nm) is much smaller than for
the carbon analogue (hexamethyl acetone)7 for which a
pronounced energy rise of the HOMO is expected to be
responsible. The 17O NMR and 13C NMR chemical shifts,
photon spectroscopy, and the pink color of bis(trimethyl-
silyl) ketone, further confirm this argument.6 Due to the
high energy of the n-orbital (HOMO) they are easily oxi-
dized by oxygen.3,4,6 Moreover, the density functional cal-
culations provided an electrostatic charge at the carbonyl
carbon of –0.005 (+0.122 for hexamethyl acetone) clearly
indicating a low degree of carbonyl polarization for the
bissilyl ketones. This is supported by an extended bond
length (1.235 Å vs. 1.220 Å) and a reduced IR vibration
frequency (1657 cm–1 vs. 1767 cm–1).7
Abstract: The first 1,2-Brook rearrangements with bis(dimethyl-
phenylsilyl) ketone, initiated after addition of different C- and S-
nucleophiles, are described. The resulting, newly formed carbanion
can be trapped with electrophiles thus paving the way for utilizing
bissilyl ketones as formyl dianion equivalents in the future.
Key words: Brook rearrangement, bissilyl ketones, formyl anion,
organolithium species, silyl migration
The intramolecular 1,2-anionic migration of a silyl group
from a carbon atom to an oxygen atom is called the 1,2-
Brook rearrangement.1,2 In fact, the migratory aptitude of
silyl groups comprises a family of [1,n]-carbon to oxygen
silyl migrations (Scheme 1). The Brook as well as the
retro-Brook rearrangements have found increasing use in
organic synthesis.
1,2-Brook
rearrangement
O
O
OSiR3
Nu
~SiR3
OSiR3
Nu
Nu
E
R1
SiR3
R1
Nu
SiR3
R1
R1
All these facts should have an impact on their chemical
behaviour, for which only limited data are available.
Thus, they have been subjected to the Peterson olefination
using trimethylsilylmethyl-Grignard forming the addition
product followed by elimination due to potassium hy-
dride.5a,b n-Butyllithium adds to bissilyl ketones in a 1:1
mixture of addition and reduction product while treatment
with alkyl Grignard reagents only affords the reduced
carbinols.5a,b Addition of electron-deficient, 1,2-disubsti-
tuted alkynes in the presence of Pd(0) leads to the corre-
sponding Z-configured 1,2-bissilyl alkenes.5c So far,
additions of nucleophiles to bissilyl ketones followed by
1,2-Brook rearrangements have not been reported. There-
fore, we planned to expand our ongoing research on cas-
cade reactions based on Brook rearrangements as key
steps8 to bissilyl ketones, which is presented in this pre-
liminary study.
E
1
O
O
OSiR3
Nu
OSiR3
Nu
~SiR3
?
Nu
E
?
SiR3
?
R3Si
R3Si
Nu
SiR3
R3Si
R3Si
E
2
Scheme 1 The 1,2-Brook rearrangement of acylsilanes and bissilyl
ketones
Acylsilanes 1 are common precursors for 1,2-Brook rear-
rangements since nucleophiles such as organometallics
smoothly add to the carbonyl group followed by silyl mi-
gration furnishing a carbanion that can be trapped electro-
philically. Indeed, this process holds particular attraction
because unusual carbanions can be generated without per-
forming a deprotonation step. So far, bissilyl ketones 2
have very rarely been studied despite the fact that poten-
tially the 1,2-Brook rearrangement can be exploited twice.
Thus, ketones like 2 can be regarded as dianion equiva-
lents based on formaldehyde.
We chose bis(dimethylphenylsilyl) ketone 7 as starting
point for these studies which we prepared by a modified
Narasaka protocol.5a We altered the preparation of dithio-
acetal 5 by conducting bissilylation in a sequential man-
ner. Thus, monosilylated dithiane 4 was first isolated and
then subjected to a second silylation step (Scheme 2). Al-
though this procedure is lengthier it offers access to non-
symmetric bissilyl ketones. In the following the resulting
bissilyldithioacetal 5 was subjected to transacetalization,
which was necessary because bissilyl ketone 7 could only
Bis(triphenylsilyl) ketone and bis(trimethylsilyl) ketone
have first been reported by Brook3 and Ricci,4 respective-
ly. Later, Narasaka et al. described bis(dimethylphenyl-
SYNLETT 2009, No. 3, pp 0429–0432
x
x.
x
x.
2
0
0
9
Advanced online publication: 21.01.2009
DOI: 10.1055/s-0028-1087535; Art ID: G32608ST
© Georg Thieme Verlag Stuttgart · New York

430
A. Kirschning et al.
LETTER
efficiently be accessed from acetal 6 and not directly from When allyl bromide was added instead of methyl iodide
dithioacetal 5. This is due to the fact that dithioacetal hy- the pure product 12 was obtained in 22% yield.
drolysis commonly proceeds under oxidative conditions.
Thiols like thioethanol and thiophenol turned out to be
equally well suited as nucleophiles (Scheme 4). Using
MeS
R
SMe
c
a
thiophenol under standard conditions a 2:1 mixture of the
rearranged product 14 and the corresponding addition
product was obtained in 80% yield whilst the pure product
15 could be isolated in 40% yield when the intermediate
carbanion was trapped with allyl bromide. Employing
thioethanol under standard conditions silyl ether 16 was
formed in 88% yield.
MeS
SMe
O
O
56%
84%
SiPhMe2
Me2PhSi
SiPhMe2
4 R = H
5 R = SiPhMe2 (88%)
6
b
d
70%
O
RSH, –78 °C to r.t.,
THF then E–X
O
OSiPhMe2
E
Me2PhSi
SiPhMe2
Me2PhSi
SiPhMe2
Me2PhSi
RS
7
7
E–X
Scheme 2 Preparation of pink bis(dimethylphenylsilyl) ketone 7.
Reagents and conditions: a) n-BuLi, THF, ClSiPhMe2; b) HMPA,
n-BuLi, THF, ClSiPhMe2; c) I2, HO(CH2)2OH; THF d) AcOH–H2O
(4:1).
H2O
CH2=CHCH2Br
H2O
14 R = Ph, E = H
15 R = Ph, E = CH2CH=CH2
16 R = Et, E = H
Scheme 4 Reaction of bissilyl ketone 7 with S-nucleophiles
With a sufficient amount (gram scale) of 7 in hand, we in-
vestigated the reactivity towards nucleophiles. We initial-
ly examined the addition of methyllithium reckoning that
the steric bulk around the carbonyl group and the electron-
ic properties exerted by the two dimethylphenylsilyl
groups could promote the silicon shift,9 which would be in
analogy to simple acylsilanes.10
Additionally, we tested cyanide as nucleophile, which
could only successfully be used when TMSCN was cho-
sen (Scheme 5). Within 30 minutes at 0 °C the pink color
disappeared and rearranged product 17 was formed and fi-
nally isolated in 32% yield. Surprisingly, the reaction only
proceeded when equimolar amounts of water were added.
Thus treatment of 7 with methyllithium at –78 °C and
gradually warming to room temperature overnight gave a
2:1 mixture of silyl ether 8 and the simple addition prod-
uct 9 in 40% yield (Scheme 3). Importantly, the desired
1,2-Brook rearrangement had taken place in the aftermath
of the nucleophilic attack. Taking into consideration that
the Brook rearrangement could be facilitated by the pres-
ence of a negative-charge-stabilizing group,11 we investi-
gated the reaction of 7 with phenyllithium. Indeed, after
one hour at –78 °C, we observed the formation of silyl
ether 10 along with the addition product 13 in 85% yield
(ratio 10/13 = 2:1). In order to further demonstrate that the
newly formed carbanion a to the siloxy group had formed,
we added methyl iodide to the reaction which gave a 1:1
mixture of silyl ether 11 and byproduct 13 in 20% yield.
TMSCN–H2O (1:1),
O
OSiPhMe2
CN
0 °C, THF
Me2PhSi
SiPhMe2
Me2PhSi
32%
H
7
17
Scheme 5 Reaction of bissilyl ketone 7 with cyanide as nucleophile
Finally, the unexpected dimethylphenylsilyl formamide
18 was isolated when NaN3 was employed as nucleophile.
A possible mechanism of its formation is depicted in
Scheme 6. After nucleophilic azide attack, an aza-Brook
rearrangement12 occured which is driven by expulsion of
nitrogen. Subsequent hydrolysis of labile intermediate 19
yielded amide 18.
MeLi, –78 °C to r.t.,
O
OH
OSiPhMe2
H
THF then H2O
+
+
Me2PhSi
Me2PhSi
SiPhMe2
Me2PhSi
Me
SiPhMe2
SiPhMe2
Me2PhSi
Me2PhSi
Me
7
8
9
PhLi, –78 °C to r.t.,
THF then E–X
O
OH
OSiPhMe2
SiPhMe2
Me2PhSi
E
Ph
13
Ph
7
E–X
H2O
10 E = H
MeI
11 E = Me
CH2=CHCH2Br
12 E = CH2-CH=CH2
Scheme 3 Reaction of bissilyl ketone 7 with organolithium agents
Synlett 2009, No. 3, 429–432 © Thieme Stuttgart · New York

LETTER
1,2-Brook Rearrangment of Bissilyl Ketones
431
then at r.t. for 1 h, it was hydrolyzed with sat. aq NH4Cl and the
aqueous layer was extracted (3×) with Et2O. The combined organic
extracts were washed with brine and dried (Na2SO4). The solvent
was removed under reduced pressure, and the crude material was
purified by bulb-to-bulb distillation under vacuum (9.3·10–3 bar, bp
145 °C) to afford product 5 as a dark orange liquid (12.9 g, 34.3
mmol; 88%).
NaN3, 0 °C to r.t.,
THF then H2O
O
O
Me2PhSi
SiPhMe2
50%
Me2PhSi
NH2
7
18
N3
H2O
O
O
~SiPhMe2
– N2
Me2PhSi
N
SiPhMe2
Preparation of 2,2-bis(dimethylphenylsilyl)-1,3-dioxolane (6)
Iodine (8.3 g, 32.80 mmol) was dissolved in a mixture of THF (50
mL) and ethylene glycol (23 mL) at r.t. To this mixture, a solution
of bis(dimethylphenylsilyl)bis(methylthio)methane 5 (3.4 g, 9.00
mmol) in THF (15 mL) was added at r.t. under argon. After 1 h, ex-
cess of I2 was reduced by adding sat. aq Na2S2O3 (50 mL) and borax
(0.025 M Na2B4O7, 50 mL). The aqueous layer was extracted with
Et2O. The combined organic extracts were washed with brine and
dried (K2CO3). The solvent was evaporated under reduced pressure,
and the crude material was purified by chromatography on SiO2
(PE–EtOAc, 99:1) to give product 6 as pale yellow crystals (1.7 g,
4.97 mmol; 56%).
Me2PhSi
NSiPhMe2
19
N
N
Scheme 6 Reaction of bissilyl ketone 7 with azide as nucleophile
Importantly, other nucleophiles like phosphines, amines,
isonitriles or alkoxides did not react or led to complete de-
composition of 7 under the optimized conditions. Also
other C-nucleophiles like organoalkynes or exchange of
lithium by Na, K, Cu(I) did not give improved results.
This is a clear indication that the carbonyl group in bissilyl
ketones shows an altered polarity with reduced reactivity
towards nucleophiles.
Preparation of bis(dimethylphenylsilyl) ketone (7)
To a solution of 2,2-bis(dimethylphenylsilyl)-1,3-dioxolane 6 (1.2
g, 3.39 mmol) in degassed AcOH (12 mL), degassed H2O (3 mL)
was added dropwise at 50 °C under argon. After stirring at 70 °C for
1 h, degassed H2O (12 mL) was added. Pink crystals were formed
after cooling to 0 °C overnight. The precipitate was filtered under
argon in vacuum in a Schlenk apparatus and washed with degassed
H2O. Pure crystals of bis(dimethylphenylsilyl) ketone 7 (707 mg,
2.37 mmol; 70%) were obtained after drying under high vacuum for
5–6 h at r.t. The material was stored at 0 °C in a glove box.
Finally, it must be noted, that yields refer to isolated
yields. These were reduced as purification was hampered
by the presence of byproducts such as the hydrolysis prod-
uct of 713 and 1,2-addition products like 9 that both
showed similar polarity to the Brook rearrangement prod-
ucts.
In conclusion, we report the first 1,2-Brook rearrange- General Procedure for the Reaction of Bissilyl Ketone 7 with
Nucleophiles Followed by Addition of Electrophiles
Bis(dimethylphenylsilyl) ketone 7 (55 mg, 0.18 mmol) was intro-
duced in a dry flask under argon and vacuum working in the glove
box. Degassed dry THF (1.3 mL) was added, and the resulting so-
ments with bissilyl ketones like 7, which is initiated after
addition of different C- and S-nucleophiles. The resulting,
newly formed carbanion can be trapped with electro-
philes. Despite the fact that the carbonyl group in 7
showed reduced reactivity compared to acyl silanes, these
studies can pave the way for utilizing bissilyl ketones as
formyl dianion equivalents in the future.
lution was cooled to –78 °C. Then, the nucleophile (0.18 mmol) was
added dropwise, and the pink solution gradually turned to yellow.
After stirring at –78 °C for 1 h, the mixture was allowed to warm to
0 °C, and stirring was continued for 1 h. Then, the electrophile (0.36
mmol) was added and, after 1 h at 0 °C, the mixture was stirred
overnight at r.t. It was diluted with hexane and passed through a pad
of SiO2 in order to remove inorganic salts. The solvent was evapo-
rated under reduced pressure and the crude mixture was purified by
chromatography on SiO2 (PE–EtOAc, 99:1).
Preparation of Dimethylphenylsilylbis(methylthio)methane (4)
To a solution of bis(methylthio)methane 3 (5 g, 46.30 mmol) in dry
THF (115 mL), n-BuLi (2.5 M in hexane, 18.5 mL, 46.30 mmol)
was added at –50 °C, and the solution was stirred at this temperature
for 1 h under argon. Then it was warmed up to –25 °C and stirred
for additional 2 h. Chlorodimethylphenylsilane (7 g, 42.0 mmol)
was added at –78 °C, and then the mixture was stirred again for 2 h
at –25 °C and at 0 °C overnight. The mixture was hydrolyzed with
sat. aq NH4Cl and the aqueous layer was extracted (3×) with Et2O.
The combined organic extracts were washed with sat. aq NaCl and
dried (Na2SO4). The solvent was removed under reduced pressure
and the crude material was purified by bulb-to-bulb distillation un-
der vacuum (1.9·10–2 bar, bp 145 °C) to afford product 4 as a deep
violet liquid (9.4 g, 38.80 mmol; 84%).
Acknowledgment
We thank the Fonds der Chemischen Industrie for financial support
and H. Duddeck, Leibniz University Hannover, for helpful discus-
sions and for performing density functional calculations (B3LYP 6-
31G*). We are indepted to K. Narasaka and M. Yamane for synthe-
tic advice.
References
(1) Review on Brook rearrangement and acylsilanes:
(a) Moser, W. H. Tetrahedron 2001, 57, 2065. (b) Ricci, A.;
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Synlett 2009, No. 3, 429–432 © Thieme Stuttgart · New York

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A. Kirschning et al.
LETTER
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Synlett 2009, No. 3, 429–432 © Thieme Stuttgart · New York

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