Reaction of silyldihalomethyllithiums with nitriles: Formation of α-keto acylsilanes via azirines and 1,3-rearrangement of silyl group from C to N

Article abstract of DOI:10.1021/ja047708o

A synthesis of α-keto acylsilanes, where 2-bromo-2H-azirine participates as a key intermediate, is reported. The reaction of silyldibromomethyllithium with aryl nitriles provides α-keto acylsilanes in good yields. Interestingly, silyldichloromethyllithium induces aza-1,3-Brook rearrangement of the silyl group in th reaction with nitriles. The rearrangement enables a three-component coupling reaction in a one-pot operation. Copyright

Full text of DOI:10.1021/ja047708o

Published on Web 06/26/2004
Reaction of Silyldihalomethyllithiums with Nitriles: Formation of r-Keto
Acylsilanes via Azirines and 1,3-Rearrangement of Silyl Group from C to N
Kazunari Yagi,† Takayuki Tsuritani,† Kazuaki Takami,† Hiroshi Shinokubo,*,‡ and Koichiro Oshima*,†
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity, Kyoto 615-8510, Japan, and
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Kyoto 606-8502, Japan
Received April 21, 2004; E-mail: hshino@kuchem.kyoto-u.ac.jp; oshima@fm1.kuic.kyoto-u.ac.jp
Scheme 1
Rearrangement of a silyl group from C to O has been successfully
applied to sequential carbon-carbon bond formation.1 We have
also disclosed a domino reaction of silyldibromomethyllithium 1a
with aldehydes and electrophiles (Scheme 1).2 The key of this
process is solvent-controlled 1,3-Brook rearrangement of silicon
from carbon to oxygen (2 to 3) prior to Peterson elimination of
â-oxidosilanes 2. This concept has been recently expanded to
multicomponent linchpin coupling reactions with silylated 1,3-
dithianes.3
Scheme 2
In contrast, there have been few reports on rearrangement from
C to N (aza-Brook rearrangement).4 With the hope to find the aza-
Brook rearrangement, we investigated the reaction of 1a with
nitriles. Here we present 1,3-rearrangement of a silyl group from
carbon to negatively charged sp2-nitrogen. In addition, a synthesis
of R-keto acylsilanes, where 2-bromo-2H-azirine participates as a
key intermediate, is reported.
tert-Butyldimethylsilyldibromomethyllithium (1a) was easily
prepared by deprotonation of dibromomethylsilane with lithium
diisopropylamide (LDA) in THF at -78 °C. An addition of
Table 1
benzonitrile and subsequent acidic workup did not furnish the
expected rearrangement product 7a but yielded deep crimson 1-silyl-
2-phenylethanedione 8a as a stable compound (Scheme 2). The
result was intriguing enough to lead us to develop a new synthetic
route of R-keto acylsilanes. Although functionalized acylsilanes
have been extensively explored in organic synthesis,5 only two
reports of R-keto acylsilane preparation have appeared in the
literature, both of which entail a multistep operation.6 It then proved
to be necessary to employ 1.5 equiv of LDA and stir more than 5
min after quenching with 1 M HCl to improve the yield. After
optimization, R-keto acylsilane 8a was obtained in 74% yield. The
reaction proceeded with aromatic nitriles bearing an electron-
donating or -withdrawing group, giving 8b or 8c in 76 or 54%
yield respectively (Table 1). Unfortunately, alkyl nitriles provided
none of the desired products. R-Keto acylsilane 8a was also obtained
in 47% yield from silyldiiodomethyllithium 1b. The lower yield
was ascribed to the instability of 1b. Interestingly, the use of
a R,R-Dichloro ketone 7b was obtained in 77% yield.
silyldichloromethyllithium 1c furnished R,R-dichloro-4-methoxy-
acetophenone (7b), which can be regarded as the rearrangement
product of the silyl group (vide infra). The triisopropylsilyl analogue
1d afforded the corresponding R-keto acylsilane 8g in 63% yield
(entry 9), whereas dimethylphenylsilyl and trimethylsilyl did not
furnish the corresponding R-keto acylsilanes.
We presumed the reaction mechanism involved an intermediacy
of 2-bromo-2H-azirine for the unexpected formation of R-keto
acylsilane (Scheme 3).7 Nucleophilic attack of 1a to nitrile produces
an initial adduct 5, which intramolecularly cyclizes to 2-bromo-
2H-azirine 9. Hydrolysis of 9 furnishes R-keto acylsilanes 8.
Chemical evidence for the presence of 2H-azirine was provided
by the action of LiAlH4 or allylmagnesium chloride giving the
corresponding aziridine 10. Furthermore, 2H-azirine 11 was
obtained as a major product in the reaction with phenyl- or
butylmagnesium bromide. An X-ray diffraction unambiguously
elucidated that direct halide displacement and not nucleophlic
addition to the C-N double bond provides 11a (Figure 1).8 Azirine
11 still has a reactive imine bond, and sequential additions of butyl
and allyl Grignard reagents to 9 provided 10c.
As briefly mentioned above, aza-1,3-Brook rearrangement can
explain the formation of R,R-dichloro ketone 7b from 1c. If this is
the case, an addition of electrophiles to the reaction mixture would
capture the resulting carbanionic species 6. In fact, treatment with
† Department of Material Chemistry, Graduate School of Engineering.
‡ Department of Chemistry, Graduate School of Science.
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10.1021/ja047708o CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 5
and tert-butyldimethylsilyl chloride in THF was added LDA at -78
°C. To the resulting mixture was added 4-methoxybenzonitrile.
Quenching with 1 M HCl afforded R-keto acylsilane 8b in 55%
overall yield.
Figure 1. ORTEP drawing of azirine 11a.
In conclusion, we have achieved a novel route to R-keto
acylsilanes from aryl nitriles with silyldibromomethyllithium. This
reaction involves 2-bromo-2H-azirine as a key intermediate, al-
lowing the synthesis of aziridines or azirines with nucleophiles.
Furthermore, we have observed novel silyl 1,3-rearrangement from
carbon to negatively charged nitrogen in the reaction with silyldi-
chloromethyllithium, which enables sequential carbon-carbon bond
formation.
Scheme 3
Acknowledgment. This work was supported by a Grant-in-Aid
for Scientific Research (No. 14703026) from the Ministry of
Education, Culture, Sports, Science, and Technology, Japan. H.S.
thanks Tokuyama Science Foundation for financial support.
Supporting Information Available: General procedures and
spectral data for compounds X-ray crystallographic file in CIF format.
This material is available free of charge via the Internet at http://
pubs.acs.org.
Scheme 4
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iodomethane provided C-methylated product 13a, along with
N-methyl imine 12a (Scheme 4).9 Benzaldehyde, which is reactive
with 6 but not with 5, afforded 13b in excellent yield. Importantly,
a single isomer of N-silyl imine 13 was exclusively obtained in
each case. The stereochemistry of the C-N double bond was
assigned as Z-configuration on the basis of NOE experiments.
Finally, we conducted this novel preparation of R-keto acylsilanes
in a one-pot operation (Scheme 5). To a mixture of dibromomethane
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(9) The addition of HMPA did not improve the yield of 13a.
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