196
Chemistry Letters Vol.36, No.1 (2007)
Conversion of (sp3)C–F Bonds of Alkyl Fluorides
to (sp3)C–Heteroatom (Heteroatom = I, SR, SeR, TeR) Bonds
by the Use of Magnesium Reagents Having Heteroatom Substituents
Shameem Ara Begum,1 Jun Terao,Ã2 and Nobuaki KambeÃ1
1Department of Applied Chemistry, Graduate School of Engineering, Osaka University,
2-1 Yamadaoka, Suita, Osaka 565-0871
2Science and Technology Center for Atoms, Molecules and Ions Control, Graduate School of Engineering,
Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871
(Received October 31, 2006; CL-061277; E-mail: terao@chem.eng.osaka-u.ac.jp, kambe@chem.eng.osaka-u.ac.jp)
1-Oct
F
1-Oct
X
2-Oct
X
(2)
MgX2
+
+
A convenient method for conversion of (sp3)C–F bonds to
solvent, 25 °C, 10 h
1.0 mmol
1.2 mmol
(sp3)C–Z (Z = I, SR, SeR, TeR) bonds has been developed.
The reaction proceeds at room temperature using magnesium
salts (Z–MgX). SN2 mechanism for substitiution of primary
alkyl fluorides with MgI2 in ether was supported by the inversion
of the stereochemistry of the carbon connecting to F.
GC yield / %
<1%
X
solvent
Et2O
Hexane
CH2Cl2
THF
DMSO
Et2O
98%
90%
73%
2%
1%
41%
<1%
I
I
I
I
I
I
Br
Cl
7%
22%
<1%
<1%
<1%
<1%
Et2O
C–F bonds are among the strongest sigma bonds frequently
found in organic molecules. Their inertness towards chemical
reactions as well as the strong electro negativity of fluorine atom
has made fluorine-containing organic molecules useful for a
variety of applications in biological and material science and,
in turn for chemists, attracts much attention to the study of C–
F activation.1 In particular, to develop new method to substitute
fluorine atoms of organic fluorides having an (sp3)C–F with
other atoms or groups has been the subject of many investiga-
tions.2 It is known that (sp3)C–F bonds can be cleaved when
treated with a strong hard acid in polar solvent. However, the
scope is generally limited to tertiary or activated alkyl fluorides
since these reactions proceed via SN1 mechanism.3 The use of
primary alkyl fluorides usually gives unsatisfactory results due
mainly to the H–F elimination, hydride shift, and skeleton
rearrangement via primary alkyl cation intermediates.4 During
the course of our study on the synthetic application of alkyl
fluorides,5 we have recently developed that C–F bonds of non-
activated alkyl fluorides can be converted efficiently into C–
Cl, C–C, C–H, C–O, C–N, C–S, C–Se, and C–Te bonds by using
organoaluminum reagents in hexane.6 Here, we wish to report
new methods for conversion of a (sp3)C–F bond of alkyl
fluorides to (sp3)C–Z (Z = I, SR, SeR, TeR) bonds using mag-
nesium reagents bearing Mg–Z bonds.
Table 1 summarizes the results obtained using other alkyl
fluorides. When cyclohexyl fluoride was treated with MgI2 in
ether, the corresponding iodide was obtained in 71% yield
along with cyclohexene (11%) (Entry 1). Only exo isomer was
obtained, when exo-2-fluoronorbornane was used (Entry 2). 1-
Fluoroadamantane and benzyl fluoride yielded the correspond-
ing iodides quantitatively (Entries 3 and 4). It should be noted
that bromo group, as well as ester group, was not affected in this
reaction system and the desired iodides were obtained in high
yields (Entries 5 and 6).
MgI2
1-Oct–F + 1-Dec–Cl
+
1-Undec–Br
1.0 mmol
+
(3)
Et2O, 25 °C, 10 h
1.0 mmol
1.0 mmol
+
1.2 mmol
1-Oct–I
98%
1-Oct–F
0%
+
1-Dec–Cl
+
1-Undec–Br
>99% recovered
>99% recovered
We examined the relative reactivities of alkyl halides (Al-
kyl–X; X = F, Cl, Br) by competitive experiments using MgI2
(eq 3). A mixture of 1 mmol of 1-fluorooctane, 1-chlorodecane,
and 1-bromoundecane was allowed to react with MgI2 (1.2
equiv.) in ether solution at 25 ꢀC for 10 h. GC analysis of the re-
sulting mixture indicated that 1-iodooctane was obtained selec-
tively in 98% yield. No evidence for the formation of other alkyl
Table 1. Preparation of alkyl iodides from alkyl fluoridesa
+
(1)
Alkyl–F
Z–MgX
Alkyl–Z
Alkyl–I
Alkyl–F
+
MgI2
Et2O, 25 °C, 10 h
(Z = I, TeR, SeR, SR)
Entry
Alkyl–I
Yield/%b
71
Alkyl–F
c-Hex–F
For example, into an ether solution of 1-fluorooctane
(1.0 mmol) was added magnesium iodide (1.2 mmol) at 25 ꢀC
for 10 h. 1-Iodooctane was obtained in 98% GC yield (eq 2).
In this reaction, only a trace amount of 2-iodooctane (<1%)
was formed, probably through 1,2-hydride shift of the 1-octyl
carbocation. When hexane and CH2Cl2 were employed as
solvent instead of Et2O, 2-iodooctane was obtained in 7 and
22% yields, respectively. The present reaction was sluggish in
THF and DMSO. When magnesium bromide was used instead
of magnesium iodide in ether solution, 1-bromooctane was
formed in 41% yield, but no reaction took place with magnesium
chloride.7
1
2
c-Hex–I
70c
F
I
1-Adamantyl–F
1-Adamantyl–I
>98
3
4
>98d
Benzyl–F
O
Benzyl–I
O
5
F
I
>98
85c
O
O
Br
F
Br
I
6
7
7
aAlkyl fluoride (1.0 mmol), magnesium iodide (1.2 mmol), ether,
25 ꢀC, 10 h. bGC yield. cIsolated yield. dNMR yield.
Copyright Ó 2007 The Chemical Society of Japan
Begum, Shameem Ara
