Fluorinative a-cleavage of cyclic ketoximes with diethylaminosulfur trifluoride:
an efficient synthesis of fluorinated carbonitriles
Masayuki Kirihara, Kanako Niimi and Takefumi Momose*
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-01, Japan
Diethylaminosulfur trifluoride effects ready cleavage of
cyclic ketoximes to fluorinated carbonitriles.
Compounds bearing a sulfur functionality 3 at the position a
to the oximino carbon reacted with DAST to cause the
fragmentation efficiently leading to a-fluoro sulfides 4. Since
a-fluoro sulfides 4 were not stable, they were subjected, without
purification, to oxidation with MCPBA. The resulting sulf-
Fluorinated organic compounds are widely used in scientific
and industrial fields. Since the preparative methods for
organofluorine compounds remain limited to a few procedures,
new fluorinating agents and methodology are required.1 Since
diethylaminosulfur trifluoride (DAST), a reagent converting
aliphatic alcohols into alkyl fluorides, has been introduced into
organic synthesis,2 there have been several reports concerning
new fluorinating methods.3–9 Among the methods, we reported
the reaction of DAST with tertiary cyclopropyl silyl ethers
causing ring opening to give allylic fluorides.10
Table 1
Run
Starting materiala
Productb
Me
Yield (%)
77
Me
F
Me
Me
NOH
1
Here we describe a novel reaction involving the treatment of
cyclic ketoximes 1 with DAST to cause a ring fragmentation
resulting in the formation of fluorinated carbonitriles 2.† The
methodology has also provided an efficient route to tertiary
fluorides or fluoroalkenes. The results are summarized in
Table 1.
The presence of substituent(s) capable of stabilising a
carbocation at the position a to the oximino carbon is essential
to obtain fluorinated carbonitriles. An oxime lacking such
substituents afforded a complex mixture (e.g. run 6 in Table 1).
In the cases of runs 4 and 5, the products were a 1:1 mixture of
stereoisomers. The results suggest that the reaction is a kind of
Beckmann fragmentation (abnormal Beckmann rearrange-
ment)11 involving a carbocation intermediate.
A postulated reaction mechanism is depicted in Scheme 1.
The first step is the nucleophilic displacement of a fluorine in
DAST by the oxygen of the oximino substrate 1 with
elimination of hydrogen fluoride. Next, the elimination of
diethylaminosulfino fluoride from the intermediate A causes the
bond cleavage and gives a carbocation intermediate B. Finally,
the fluoride ion attacks B to afford the fluorinated carbonitrile 2
(path a). In the case of compounds lacking substituents to
stabilise the a-carbocation, the reaction proceeds through a
mechanism similar to that of the ‘normal’ Beckmann rearrange-
ment. The carbon–carbon bond anti to the oximino leaving
group in the intermediate A migrates to the nitrogen atom to
afford the carbocation C. The fluoride ion attacks C to give an
unstable compound D, which leads to a complex mixture (path
b).
CN
CN
NOH
F
2
91
CN
HON
Ph
Ph
Ph
3
4
75
Ph
F
Me
Me
Me
Me
Me
Me
69c
CN
F
H
NOH
Me
NOH
Me
F
5
63c
CN
H
AcO
AcO
HON
complex mixture
6
—
a Oximes were prepared from ketones by reaction with hydroxylamine. b All
compounds were characterised on the basis of mass, IR, 1H and 19F NMR
spectral data. c A 1:1 mixture of stereoisomers.
N
CN
C
R1
R2
F
F –
R1
R2
path a
Et2N
b
+
S
HON
O N
F
F
a
R1
R2
R1
R2
B
2
–Et2NSOF
Et2NSF3
–HF
F
+
N
N
R1
R2
R1
R2
F –
1
A
path b
C
D (unstable)
complex mixture
Scheme 1
Chem. Commun., 1997
599
Kirihara, Masayuki
