- Email: [email protected]
Preparation and synthetic utility of fluorinated phosphonium salts, bis -phosphonium salts and phosphoranium salts [1]
Journal of Fluorine Chemistry, 23 (I 983) 339-357 Received:
January
8, 1983
; accepted:
PREPARATION AND SYNTHETIC PHOSPHONIUM
11, 1983
January
UTILITY
339
OF FLUORINATED
SALTS AND PHOSPHORANIUM
SALTS
PHOSPHONIUM
SALTS,
BIS-
rli
DONALD J. BURTON
Department
of Chemistry,
University
of Iowa, Iowa City,
Iowa 52242
(U.S.A.)
SUMMARY
The reaction
of tertiary
rapid and high yield
synthesis
salts, -bis-phosphonium ful precursors Examples
phosphines of various
types of fluorinated
salts and phosphoranium
to fluorine-containing
of the preparation,
of these novel
with fluorohalomethanes
reagents
salts.
ylides,
mechanism
a
phosphonium
These salts are use-
carbenes
of formation,
provides
and methide
and synthetic
ions. utility
is described.
INTRODUCTION
The Wittig paration
Reaction
of olefins
is one of the most widely
and substituted
one to select
the substituents
proper choice
of ylide
attached
and aldehyde
allows one to unequivocally
predict
used routes
olefin derivatives. to the olefinic
or ketone,
and more
the position
for the pre-
It readily center
permits
via the
importantly
of the alkene
it
center
in
the final product.
R ~-CR'R' 3
+
R3C(0)R4
For the normal Wittig
R3P0
+
R1R2C=CR3R4
route to be successful
plished;
(1) successful
tertiary
phosphine
removal
---t
alkylation
to produce
of an a-hydrogen
the required
phosphonium
from the phosphonium
thus, at least one a-hydrogen
two key steps must be accom-
of the appropriate
must be present
substrate salt;
salt to produce
by the
(2) selective the ylide
in the phosphonium
-
salt pre-
cursor.
0022-1139/83/$3.00
0 Elsevier Sequoia/Printed
in The Netherlands
340 R3P:
R'R*CHX
+
[R LHR'R*]X3
+
Several years potentially
general
However,
+
-+
and useful
CHF2X
phosphines;
and its abstraction
salt; an approach ylide;
that avoided
an
alternative chemistry
in situ -reactive
or generated
focus attention will detail
can be made.
the extensions
Although ium salts
work
we have prepared
[2], for illustrative
[(R~N)~&Fc~~]c~are representative fluorohalomethyl
capture
of the ylide
or
produced
the ylide
of the mechanistic
It will
of these reagents Indeed,
and
it's only
approach
to these
of the initial mechanistic salts and phosphoranium
of fluorohalomethyl
[R3$CF2Br]Br-,
for discussion and synthetic
salt chemistry
in its
process.
in these areas will be briefly
purposes
an
some of the mechanistic
intelligent
a wide variety
have been selected
phosphonium
the
of several
to bis-phosphonium
and some of our preliminary
to produce
interpretations.
that a designed
an
reactions
in situ
Further extrapolations
[R3P-CF2],
failed.
of the phosphonium
stabilization;or
understands)
by
was not very+ac_idic
to solve these problems.
utility
reasons:
alkylated
was needed that avoided
via a dissociative
(or hopefully
[Base H]'X-
at pregeneration
that either mimicked
our approach
on the synthetic
steps in these reactions
suggested
of ylide
some of our mechanistic
when one understands
ylides
permitted
the ylide
and ylide.
Wittig
(c) the ylide
in the preparation
intermediate
This report outlines
or messy;
proton abstraction
mechanism
Our
for the following
in the [R3PCF2~]X-
that an approach
and a route that either
provided
success
and all attempts
reaction
+
CR~&F~]
were not easily or cleanly
(b) the hydrogen
obvious
as a
olefins
above for a "normal"
base_
by base was difficult
Thus, it became
olefins.
of the difluoromethylene
outlined
derivatives
SN2 type of displacement
Reaction
is:
met with little
was found to be very unstable
the Wittig
of difluoromethylene
precursors
[R3&~2~]~-
this approach
[Base H]+X-
route to fluoromethylene
strategy
+
+
to investigate
likely approach
(a) the difluoromethane tertiary
[R3LR'R*]
on the preparation
the normal
the most
R3P:
Base
of the required
If one follows reagent,
[R LHR'R*]X3
ago we decided
initial work focused the preparation
+
[3].
ideas
salts,
reviewed. phosphon-
[Ph36CFBr2]Br-,
and
in this paper as they types encountered
in
341 RESULTS
AND DISCUSSION
Bromodifluoromethylphosphonium In contrast phosphine reacted
literature
reports
on the failure
of triphenyl-
to react with CF31 and CFC13, we found that triphenylphosphine
readily with CF2Br2
essentially glyme
to earlier
salts
a quantitative
+
(usually within
precipitates
CF2Br2
-$
30 seconds)
salt (I)
of the phosphonium
salt (I)
solvents
Ph3P:
in diglyme yield
and can be easily
[Ph3iCF2Br]Br-
isolated
to give
In
[4]. by
4
- lOO%, (I) It is easily
filtration.
proper attention procedures,
it is easily
A similar the analogous
reaction
by water or protic solvents
+
solvents
and Schlenk
but with
transfer
and readily manipulated. with tris-dimethylaminophosphine
phosphonium
(Me2N)3P:
hydrolyzed
to the use of anhydrous
salt (II)
D(;,
CF2Br2
[5].
In contrast
and CF2Br2
to (I),
salt
gives
(II)
is
[(Me2N)3&F2Br]Br(II)
not hydrolyzed OH-.
by water
or protic
solvents,
In fact, this type of solvolytic
types of fluorohalomethyl triphenylphosphonium alcohol;
phosphonium
derivatives
(b) trialkylphosphonium
not by alcohol; by neither
but is hydrolyzed
behavior
salts that we have worked
are readily
hydrolyzed
derivatives
are hydrolyzed
(c) tris-dialkylamino
by aqueous
[6] is characteristic
phosphonium
ofall
with:
(a)
by water and by water
derivatives
but
are hydrolyzed
water nor alcohol.
+ e
[(R2N)3PCF2XlX Mechanism
example
mechanism
salts
[8].
the formation
of a typical
of formation
have proposed
decreasing
[71
ease of hydrolysis
of salt formation
At first glance another
[Ph3&F2X,X-
of (I) and (II)
SN2 displacement
of (I) and (II)
the following
sequence
would appear
type reaction.
is much more complicated, to explain
the formation
to be
However, and we
of these
the
342 +
R3P:
CF2Br2
+
[R3iBr]
+
(positive halogen abstraction)
[CF2Br]-
R = Ph, Me2N
[CF2Br]-z
R3P:
[:CF2]
+
Br-
(carbene
formation)
&i-&2]
(carbene
capture)
+
[:CF2] 3
+
+ +
[R3PBr]
-
[R3PCF2Br]Br-
+
R3P: (positive halogen abstraction)
The key initial
step is abstraction
attack on carbon (CF2Br2)carbene wise formation distinguish
(SN2)-and
may be formed 2 of [CF2X]-
between
electrophilic tertiary halogen
from
or continue
[R3PBr] or CF2Br2 to complete
Evidence
Ph3P:
+
CF2BrI
If the mechanism
(IV).
preferential
[Ill.
proposal
-$&
[Ph3cCF21]Br-
of formation
+
captures
positive
and initiate
is [lo]:
[Ph3&F2Br]I-
(III)
(IV)
2
1
of (I) involved
SN2 attack
that (IV) should be the predominant leaving
as noted above,
The formation
carbene mechanism
pathway The
by the nucleophilic
- which
the salt formation
with this mechanistic
- based on the better However,
simplicity.
captured
ylide
- we cannot
- the stepwise
with CF?BrI
one would anticipate
bromide.
rather than via step-
process.
consistent
(a) Reaction
product
is subsequently
- not
In this case
to carbene
pathway
for operative
to give the phosphonium
the chain
process
by dissociation
or stepwise
scheme merely
difluorocarbene
phosphiye
halogen)
of difluorocarbene.
a concerted
followed
a concerted
is used in the preceding
of Br+ (attack on
formation
[91
of (III)
group ability
the predominant
as the major
of iodide compared product
product
on carbon,
or exclusive to
is (III) - not
is consistent
with the
- since in the initial or final step one would anticipate
abstraction
of the more polarizable
iodinecomparedto
bromine
343 (b)
Reaction
+
Ph3P:
in the presence
CF2Br2
w
H20
of proton donors
[Ph3iCF2H]Br-
+
CF2HBr
55% Since hydrolysis [Ph3&F2H]Br-
involved
of the intermediate
SN2 attack
hydrolysis
of (I) gives only CF,HBr,
can only be explained
and protonation
on CF2Br2,
[12].
of
ylide
formation
If the mechanism
only the methane
of (I)
would be anticipated
prepared
cursors
to the corresponding
reagents
makes these salts suitable difluoromethylene
from (I) or (II)
halogen
from commercially
of (I) and (II)
readily
phosphine
ylide
formation,
as the
of (I) and (II)
The availability
capture
the formation
via cakbene
product.
Ylide reaction
positive
20%
permits -in situ
of the ylide
[R3iCF2Br]Br-
formation
R3P:
e
Abstraction
of the appropriate aldehyde
t[RAP-CF~]
+
or
and attractive
ylides.
by a second equivalent
by the appropriate +
available
preof
of the tertiary ylide
and -in situ
or ketone
+ [R3PBr]Br-
Cl31
R= Ph, Me2N [ ,,;-,,;I
Illustrative given
examples
approach
F2C=C<
+
of the synthetic
comments
applicability
+
on the mechanism
are needed
applicability
of
(I)
and (II) are
of (I)
(a) The reaction
of this reaction
olefins. or (II)
with a second equivalent
equilibrium
reaction
Thus,
is always an excess
there
important Wittig olefins
[13] - with the equilibrium
to consider
reaction readily
of R3P present
this equilibrium
react with tertiary
of this aldehyde
with PhCOCF3
in Table
with(Me2N)3P
[16].
dehalogenation
-far to the left.
ketones
phosphines
[15],
Similarly,
II is due to rapid reaction
this type of [14] and Thus,
in
the low yield of this ketone
can be often circumvented
of the pre-generated
It is
is due to rapid and destructive
with Ph3P.
This problem
of R3P is an
in solution.
when designing
- since some polyfluorinated
I the low yield with C6F5CH0
reactions
and its synthetic
to permit one to get the best results with this
to difluoromethylene
Table
R3P0
I and II.
in Table Several
>c=o
+
phosphonium
via
salt with a metal [15:
344 TABLE
I
2 Ph3P
f
CF2Br2
+
>C=O-$$+
>C=CF
2
+
Ph3PO
+
Ph3PBr2
>c=o
>C=CF
C6H5CHO
C6H5CH=CF2
65
C6F5CHO
C6F5CH=CF2
20
C6H5COCF3
C6H5C(CF3)=CF2
85
C6H,,COCF3
C6H,,C(CF3)=CF2
90
C6H5COC2F5
C,H,C(C,F,)=CF2
82
cH3(CH2)6CH0
CH3(CH2)5CH=CF2
72
m-BrC6H4COCF3 -
m-BrC6H4C(CF3)=CF2
83
C6H5COCH3
C6H5C(CH3)=CF2
TABLE
% yield
2
2
II
2(Me2N)3P
+
CF2Br2
+
bC=O-$
>C=CF
2
+
(Me2N)3P0
+
(Me2N)3PBr2
x=0
>C=CF
C6H5COCH3
C6H5C(CH3)=CF2
81
C6H5COC2H5
C6H5C(C2H5)=CF2
82
(C2H5)2C0
(C2H5)2C=CF2
75
0
0
% yield
2
=CF2
71
(CH3j2C0
(CH~)~C=CF~
60
C6H5COCF3
C6H5C(CF3)=CF2
25
=0
345 (b) The choice of which electrophilicity typical
of the carbonyl
aliphatic
aldehyde
aldehyde
(PhCHO),
successfully activated However,
ylide system to utilize
(PhCOCH3)
ketones
olefin.
and ketones Obviously,
nonproduct.
ylide
[17], all
converted
can be easily because
pared to Ph3P:, the more reactive ployed only with obstinate
reaction
ketones
olefinic
[(Me2N)3P-CF2]
noted above and the enhanced
acid-base
a typical
are successfully
system most aldehydes
yields
However,
I, a
aromatic
to the
Thus, by the proper choice of the ylide
CF2=C< type olefins.
(c) With highly enolizable
in Table
a typical
gives only traces+of
with the more nucleophilic
types of non-activated
Thus,
by the
a_ctivated (trifluoromethyl)
react with [Ph3P-CF2].
ketone
difluoromethylene
problem
component.
[cH~(cH~)~cHo],
and typica!
is dictated
converted
reactivity
ylide
to
of the equilibrium of (Me2N)3P:
system
is generally
comem-
substrates.
substrates,
these basic ylides
(which quenches
the ylide)
undergo
an
and gives poor
of olefin.
[(Me2N)3GCF2]
However,
+
cyclopentanone
successful
formation
type can be readily
+
[(Me2N)&F2H]
+
of difluoromethylene
accomplished
enolate
olefins
by an ylide-carbene
of this
reaction
[18,
191. (d) This route to the difluoromethylene and is not characterized amounts
of fluoride
addition formed
ion.
and fluoride
olefins
avoided
of the isolated
product)
route.
substituted
Similarly,
the HF addition
(Table I) in contrast encountered
this method
yield of olefin
product -via the [4].
derivatives
have been reported
sensitive [Zl].
[20] and salt
olefin
of fluoride-ionisomerization
salt method
of fluoroolefins
Similar
[21] in the acetate
gives only the terminal
to the problems
with the acetate
the preparation
substituted
derivatives
PhCOCF2CF3
For
this ketone gives mainly
route to the ylide
were found with chloro
trifluoromethyl
of the initially
(Table I) gives an excellent
sodium chlorodifluoroacetate results
isomerization
with this approach.
salt route, whereas
via the phosphonium (ss%
is a mild, clean route of any significant
Thus, many of the probl,ems of HF
ion catalyzed
are easily
example,m-SrC6H4COCF3
ylides
by the formation
[20].
Other examples
to fluoride
ion fi
of
346
(e) The reaction
can be applied Ph3P ,m*
EtC(O)(CF2)2C(O)Et
to polyfunctionalized
F2C=$(CF2)2;=CF2 Et
+
derivatives:
enone
Et
6%
50%
[=I
Ph3P m
PhC(O)(CF2)3C(O)Ph
F2C=F(CF2)3F=CF2 2
2
Ph
+
enone
Ph
16%
57%
Dihalofluoromethylphosphonium
Typical
Ph3P:
examples
+
CFBr3
salts
of salts of this type are illustrated
below:
[Ph3&FBr2]BrS
-
(VI t (Me2N)3P:
+
CFC13
d
[(Me2N)3PCFC12]C1 (VT)
With the more polarizable (Ph3P) affords
methane
the phosphonium
with Ph3P to give a phosphonium in the preparation phosphine
must
phosphonium ion pair.
R3P:
salts
+
--t
utilized
of formation
abstraction
of salts of this type
of bromodifluoromethyl-
of positive
halogen
the mechanistic
~R,;;x]cFx,;~,,
[24].
to produce
pathways
an
diverge.
[R~&Fx~]x-
X = Br, Cl
R = Ph, Me2N
CF2x2,
conditions
salt formation
step in the formation
at this juncture
CFX3
Since the methide
to accomplish
- namely,
However,
phosphine
CFC13 does not react
[23]; hence the more halophilic
step in the mechanism
to the initial
the less halophilic However,
salt under the normal
of these materials
be employed
The initial is similar
(CFBr3),
salt (V).
ion produced
it recombines
from CFX3 is longer
with the halophosphonium
attack on the phosphonium
center)
lived than the ion fror
cation
(via nucleophilic
to give the phosphonium
salt.
347 Evidence
consistent
(MIZ~N)~P:
+
with this mechanistic
0r_EtOH
cFci3
of traces Since
between
(VI) is stable
it would
of (VI).
not undergo
the halogen reaction
(Me2N)3P
if (VI)
further
of the methane
between
the methide
cleavage
phosphine
+
CFBr3
+
Similar
(SN2).
of the chain-extended
CF2=CFCF3
tertiary
phosphine
__)
ylides
+
[Ph3&FBr2]Br-
+ [(Me2N)3PCFC12]Br -
Table
III
summarizes
fluoromethylene out stepwise
olefins ylides
CFBr2
[Ph3&FBr]
+
'CF
3
salts with a second mole of
examples Again,
[26]
and
+
(Me2N)3PC12
of the preparation the reaction
of bromo
may be carried
obtained
are readily
The fluorohalo-
are possible.
reagents
[30], zinc [30], or copper
for the preparation
Ph3PBr2
In the case of the bromofluoro-
procedure.
are usually
+
[(Me2N)3&FC1]
via this route. -
olefins
[251
F
bromofluoromethylene
both (E) and (I) isomers
bromofluoromethylene
is electrophilic
(via capture of mechanistic scheme.
/
dehalogenated
are not stereospecific
isomers
[29], Grignard
+
(Me2N)3P:
or -via a one-pot
methylene
useful entry
Ph3P:
+
if the
[27].
some illustrative
olefins
methylene
geometrical
can be further
with is on
olefin
with the proposed
to give the respective
chlorofluoromethylene
experiments
as acompetitive
of dihalofluoromethylphosphonium
(V) and (VI)
Salts
be formed via
Similarly
F'
utility
cannot
- that initial attack
'c=c
Synthetic
is observed.
and the trihalofluoromethane
ion) is again consistent
Ph3P:
to CHFC12.
of a fluoroolefin
the formation
out in the presence
No (VI)
had been formed -via SN2 attack on CFC13,
and not on carbon
tertiary
agent,
is carried
is observed.
lead to the same conclusion
out in the presence
trapping
and CFC13
to both EtOH and H20, the CHFC12 Thus,
CFBr3 and (Me2N)3P
carried
95%
of EtOH or H20. only CHFC12
hydrolysis
is:
CHFC12
H2° When the reaction
interpretation
and where
in w 1:l ratio converted
possible,
[2B].
into vinylic
[30] reagents,
of polyfunctionalized
the
Since these lithium
they provide
a
fluorinederivatives.
348 TABLE
III +
CPh3iCFBr2,Br_
Ph3P
+
>C=O
solvent_*>C=CFBr
+
Ph3PO
+
Ph3PBr2
>c=o
>C=CFBr
% yield
C6H5CHO
C6H5CH=CFBr
70
C6H5COCF3
C6H5C(CF3)=CFBr
97
C6H5CH2COCF3
C6H5CH2C(CF3)=CFBr
59
C6H5COC2F5
C6H5C(C2F5)=CFBr
65
CF3COCF3
(CF3)2C=CFBr
80
C6H5COCH3
C6H5C(CH3)=CFBr
45
C3F7COC3F7
(C3F7)2C=CFBr
79
*Solvents
such as THF, CH3CN,
solubility
of the carbonyl
The phosphine completely
An alternative
of (VI)
to the other
generation
occurs
stabilized
ylide
with zinc metal
[(Me2N)3&FC12]C1-
Zn
solution
of this reagent
+
to the "free" ylide
loses activity cellent
[(Me2N)3i-CFC1].
with typical
examples).
carbonyl
Only highly
+
of a metal-
However,
substrates
enolizable
ZnCl2
The free ylide
this metal-stabilized
(- 1% per day) over one month.
reactivity
illustrative
is -via use dehalo-
[(Me,N),iCFClZnCl]Cl-
[(Me2N)3PCFCl]
life less than l/2 hr. [32], whereas
salts.
is remarkable
IJ t- (VII)
compared
[27] and is
phosphonium
With salt (VI) facile
to give a stable
The stability
+
reported
of these salts, however,
(as noted earlier).
[31].
on the
has been reported
previously
mode of dehalogenation metal
depending
substrate.
dehalogenation
analogous
of an active
CHCl3 were utilized
has a half-
reagent
slowly
(VII) exhibits
(cf. Table
substrates
IV
for
give poor
ex-
349
IV
TABLE
t [(Me2N)SPCFC12]C1-
+
Zn(Cu)
+
THF F
X=0
>C=CFCl
>c=o
>C=CFCl
% yield
C8HSCHO
CSHSCH=CFCl
100
CSHSCOCFS
CEHEC(CFS)=CFCl
100
CEHSCOCHS
CSHSC(CHS)=CFCl
70
CH3(CH2)SCH0
CHS(CH&H=CFCl
0 =o
0
CF3C02CH3
results
- due to protonation
(VII) dissociates
is easily
the preparation
of chlorofluoromethylene
The metal dehalogenation of metal-stabilized laboratories.
phine
Preliminary
(V).
examples
mixture.
converted
Some of our preliminary
and some typical in Table
indicate
by the tertiary
can be readily
of
is storable, of choice
and for
salts and the formation
under active
of several
in the reaction
that are attacked
approach
method.
route of phosphonium
results
that
olefinating
olefins.
aspect of this mode of approach
is present
is the actual
in high yields,
re-
we assume
scaled up, it is the method
is currently
and will be the subject
strates ylide
ylides
90
Since the stereochemical
which
prepared
can be readily
important
18
(VII) or the 'free' ylide,
to the 'free' ylide,
(VII)
Since
of the ylide.
with either
its preparation
method
=CFCl
CFSC(OCHS)=CFCl
sults are identical
species.
100
investigation
in our
that it is a generally
useful
reports
Thus, carbonyl phosphine
to olefins
results
the utility
in the near future.
is that -no excess
tertiary
One phos_
or olefinic
sub-
and fail in the normal via this alternative -
with salt (I) have been reported of this approach
are illustrated
350 TABLE
V t
RCOR'
Metal
(M)
+
[Ph3&FpBr]Br-
+
&RR~c=cF~
MBr2
+
Ph3PO
RCOR'
RR'C=CF2
Cd
Hg
Ph3Pa
C6H5C(0)CF2C1
C6H$(CF2Cl)=CF2
76
21
25
C6F5C(0)CF3
C6F5C(CF3)=CF2
83
71
0
C6F5CH0
C6F5CH=CF2
62
41
20
C6F5C(0)CF2Cl
C6F5C(CF2C1)=CF2
72
64
0
(a) Yield of olefin when Ph3P was used as the dehalogenation
-Bis-phosphonium
Although (VI)
salts
our work with phosphonium
continues,
to other
we have recently
interesting
This work
and novel
is of recent
vintage
with the fluorohalomethyl
salts such as (I), (II), (V), and
begun to examine
and obviously
phosphonium
salts.
However,
and synthetic
outline
some of the interesting
features
the mechanistic
difluoromethylene
ylide
second equivalent
of the tertiary
equilibrium
we would like to
ideas on this subject
of these reactions
and to
that are being
involved
scheme
abstraction phosphine
for the preparation of Br+ from to establish
of the
(I) or (II) -via a the following
[13].
[R3&F2Br]Br‘
+
R3P:
the importance
cation
to donate
,k
[R3iBr]B;
+
[R3&F2]
of this equ ilibrium is the ability of the I BrT back to the ylide - thus preventing rapid
dissociation
[33] and decomposition
to the ylide
which
been noted.
intermediates. as the work
in our laboratory.
As noted earlier
[R3PBr]
synthetic
not as complete
some of our mechanistic
We $elieve
these salts as precursors
phosphorus-fluorine
present
investigated
reagent.
do not involve
of the ylide. R3PBr2,
Indeed,
no stabilization
in other routes of the ylide
has
351 In additionto suggests ylide
recapture
an alternative
on the phosphorus
,3&F,
of Br+bythe
ylide,
the above equilibrium
mode of reaztion -namely, atom of [R3PBr]
+
[R3iBr]Br-
nucleophilic
attack
to give a fi-phosphonium
also
by the
salt.
tt [R3PCF2PR3]Br-
e
-bis-phosphonium
salt
(VIII) When R = Ph or Me2N, little b&-phosphonium [lo].
However,
observed,
salt formation
when R = alkyl, -bis-phosphonium
and the -bis-phosphonium
is observed
salt formation
salt can be easily
is readily
and rapidly
formed
in
high yield.
2 Bu3P:
+
CF2Br2
Again,
the key mechanistic
1341.
Does the step involve
by a second equivalent
[Bu3&F2Br]Br‘
[Bu3&FZiBu3]2
e
question
is the second step in this sequence
SN2 attack on carbon or abstraction
of the tertiary
+
Br-
of halogen
phosphine?
Bu3P SN2 \
[Bu3~CF2~Bu3]2
Br-
/ tBu3PCF2
+
When the reaction presence
t of [Bu3PCF2Br]Br-
of PhCH2COCF3
phosphonium the positive capture
+ [Bu3PBr]Br
salt were observed. halogen
of the ylide
with Bu3P is carried
[35], the difluoromethylene
abstraction
These products mechanism
and the reduced
of any SN2 type reactions
[Bu3&F2Br]Br-
t
PhCH2COCF3
and the reduced
are only consistent
- the olefin
ketone.
Thus,
capture
again we note the
in these processes. Bu3P H
CF2=;CH2Ph
+
CBu3&F2HlBr‘
cF3 50%
with
is formed via
salt is formed -via proton
from the enol of the benzyltrifluoromethyl absence
out in the
olefin
50%
352 The b&-phosphonium interesting
mixed
salt preparation
opens up many new routes to
salts as well as mixed valence
in the two illustrative
[Et3LFZBr]Br-
+
species,
as shown below
examples.
Bu3P:
__t
[Et3&FZiBu3]
2 Br-
[lOI
70%
[Bu3&F2Br]Br-
A detailed
+
(Et0)3P:
investigation
exciting
Phosphoranium
[Bu&F2P(0)(OEt),]Br-
+
EtBr
of the scope of these and other -bis Species
Our preliminary
now in progress. anticipate
w
work suggests
Cl01 iS
that we can undoubtedly
and novel results.
salts
Our preliminary previous related
work with -bis-phosphonium salts outlined in the led us to explore related work with salts such as (V) and
section
derivatives.
anticipate
Again
(based on the earlier
that nucleophilic
the bromophosphonium
cation would
[Ph3iCFBrp]Br-
+
work),
one might
attack of the bromofluoromethylene
Ph3P:
lead to a -bis-phosphonium
e
[Ph,&;Br]
+
ylide on
salt.
[Ph3iBr]Br-
1 [Ph3&FBr~Ph3]2
Br-
(IX) There
is, however,
salt (IX) there carbon
one important
atom - whereas
abstracted
phosphine
is added,
carbon perhaps
atom.
(IX)
(VIII)
present
ZBr-
+
Ph3P:
-+
Thus,
this reactive
to give the fluorine-containing
CPh3&FBriPh3]
between
halogen
In
easy abstraction
if another bromine
phosphoranium +- + [Ph3PCFPPh3]Br(X)
and (IX).
on the methylene
in (VIII) one would not anticipate
of Ff from the difluoromethylene of tertiary
difference
is still a polarizable
salt,
+
equivalent
can be
(X) [%I.
Ph3PBr2
353
In fact, one finds that the bromine
in (IX) is much more reactive
bromine
in (V) and even with a deficiency
of tertiary
rapidly
formed from (V) in an appropriate
solvent
With this information fluorine-containing procedure
in hand, the obvious
questions
salts be directly
from fluorohalomethanes?
Can the cheaper
these questions
Fortunately
is affirmative
CFC13 can be used with trialkyl
3 Ph3P:
+
+
CFBr3
for the synthetic
as outlined
below
phosphines,
than the (X) is
[37].
phosphoranium
these preparations?
phosphine,
are:
can
formed via a one-pot CFC13 be utilized in chemist,
[37,38].
the answer Either
to
CFBr3 or
such as Bu3P; CFC13 does not
[Ph3iCFzPh3]8r-
+
Ph3PBrp i
+
Bu3PBr2 4
+
Bu3PC12
90%
+- + +
3 Bu3P:
CFBr3
---t
[Bu3PCFPBu3]Br80-90%
+
3 Bu3P:
CFC13
d
[Bu~&FLJ~]C~-
95%
react with Ph3P as noted earlier. ium salts are rapid, able commercial
clean,
chemicals.
use in the preparation A unique
fluorides.
R &R1R2 3
ylides
+
are treated
R3C(0)X
that the fluorine-containing reaction phonium olefin.
with E-acyl salt.
yields
from readily
avail-
find extensive
compounds. has already
of phosphoranium
to the normal
to form the phosphoran-
in our estimation,
of these reagents reaction
- namely,
In contrast
phosphonium
and give excellent They will,
of fluorinated
application
our laboratory
These reactions
acylation
been discovered
reaction
with acyl halides,
in
salts with E-acyl observed
when
we have discovered
[R ~cR'R~C(~)R~]X3
-
phosphoranium
fluorides
Base hydrolysis
salts rapidly
to give stereospecifically give stereospecifically
undergo
a Wittig
the (I)-phos-
the (E)-1-hydro-E-
354
+
[Bu3&FiBu33x+ RFC(O)F
+
B"3p\
C=C
F'
,F 'R
X-
+
Bu3P0
F
(Z_)-phosphonium salt
I
H
H20/0H-
\CJF F' ' RF (E)-l-hydro-E-olefin . Table
(VI) gives
of fluoroolefins for several reaction
directly
reasons:
(c) the olefin
of these systems full details
TABLE
from acyl fluorides.
(d) the product
isomer olefins
further -via conventional be reported
(b) the
as only the (r)-
in at least some of the can be readily metallated
is currently
A detailed in progress
study and
in the future.
VI
+- + [BU~PCFPBU~]X-
is attractive
salt need not be
chemistry.
systems
of preparation
available;
stereospecifically
less-stable
as well as related
will
The method
are readily
the ($)-phosphonium
is obtained
the thermodynamically
[29] and elaborated
of this novel method
(a) all precursors
(RF = CF3, C2F5);
cases
examples
is a one-pot procedure-
isolated; isomer-
illustrative
1) RFC(0)F
H +
2) NaOH/H20
1
/F
F,C=c\ RF (E)-olefin
RF
(E)-olefin
% yield
cF3
CF3CF=CFH
45
CF3CF2
CF3CF2CF=CFH
62
CF3CF2CF2
CF3CF2CF2CF=CFH
52
CF2Cl
CF2C1CF=CFH
50
CH302CCF2
CH302CCF2CF=CFH
20
CF3(CF2)20CFCF3
CF,(CF,),OCF(CF,)CF=CFH
49
355 In sunmary, intermediates olefins
these easily
via the nucleophilic
the generation
reagents
[25,41].
containing
reaction
difluorocarbene. taining
transfer
rather
ylides;
agents
intermediates
derivatives
for
[39]; they serve as
[40] as well as chain-extension
the key reactions
are either
has already of fluorine
of these reagents
reaction
they are also useful
difluorocarbene
than attack on carbon,
to the preparation
development
are useful
types of fluoromethylene
are halogen
and the key fluorine-
fluorohalo
The use of these interesting
phosphorus
approaches
phosphonium
Mechanistically,
processes
materials
of various
of the electrophilic
useful fluorohalomethyl
abstraction
prepared
for the preparation
methide
ions or
and novel fluorine-con-
provided
some new synthetic
compounds,
and the further
has a promising
and bright
future.
ACKNOWLEDGEMENT
I would write
like to thank Professor
this overview
extended
of our work
to the National
Scientific
Research
least,
co-workers,
and interesting
Foundation
I would
whose
only for their excellent zest for chemistry
in this area.
Science
who have generously
Last, but by no means my excellent
D.W.A. Sharp for the invitation Our sincere
skills,
of
our work in this field.
like to express
names are included
technical
thanks are also
and the Air Force Office
supported
that they have provided
to
my sincere
thanks
in the references,
but also for the enthusiasm in making
our laboratory
to
not and
a fun
place.
NOTES AND REFERENCES
Taken
in part from a lecture
Symposium
presented
of FluorineChemistry,
O-5; Journal
Fluorine
M.J. Van Hamme, Resonance,
D.J.
Chemistry, Burton,
at the 10th International
Vancouver,
Canada, August
1982, Abstract
-21 (1982) 47.
and P.E. Greenlimb,
Organic
Magnetic
-11 (1978) 275.
cf. to V.V. Tyuleneva, E.M. Rokhlin, and I.L. Knunyants, Russian Chemical Reviews, -50 (1981) 280 for an excellent review of fluorinecontaining Unpublished Journal
halogenomethylene
work of D.G. Naae; cf. also D.G. Naae and D.J. Burton,
of Fluorine
D.G. Naae and D.J. Unpublished
ylides.
Chemistry Burton,
L-971)
Synthetic
work in this laboratory.
123. Communications,
2 (1973) 197.
356 7 The solvolytic period
behavior
alcohol
may result
ACS Bicentenial Abstraction
Daytona
Symposium,
Beach,
Florida,
may capture
whichever
moiety
of even the less reactive
Phosphonium
Salts'
New York, April 1976,
presented February,
positive
donates
over
salts.
presented
'Positive
at the
Halogen
Containing
at the 5th Winter
FluorineConference,
1981.
halogen
a
to water of
- The Key to Phosphorus-Fluorine
Intermediates'
9 The ylide
hydrolysis
(days) of exposure
of Halogenated
Reactions
Synthetic
periods
in slow hydrolysis
'Chemistry
8 Lectures,
here refers to significant
Prolonged
of hours.
+ either
from [R3PBr] or CF2Br2
Br+ does not change the overall
-
mechanistic
interpretation. 10 Unpublished 11 Control undergo
halogen
reaction 12 Control CF2HBr
work of H.S. Kesling,
experiments
exchange
conditions
that
of Iowa. and/or
(III)
at the halodifluoromethyl
(IV)
carbon
do not
under the
used [lo].
experiments+have
established
to give [Ph3PCF2H]Br-
(1975) 3789 for discussion F.E. Herkes,
that Ph3P does not react with
under the reaction
13 cf. D.G. Naae, H.S. Kesling,
14 D.J. Burton,
University
have established
and D.J. Burton,
of the reversible
conditions
Tetrahedron equilibrium
and K.J. Klabunde,
J. Amer.
[lo]. Letters, in this step.
Chem. Sot., 88
(1966) 5042. 15 D.J.
Burton,
and D.G. Naae, J. Fluorine
H.S. Kesling,
Chemistry,
-18
(1981) 293. 16 F. Ramirez,
C.P. Smith,
and S. Meyerson,
Tetrahedron
Letters,
(1964)
3651. 17 The irder of nucleophilicity
of these ylides
is [Me2N)3i-tF2]
.
[Ph3P-CF2]. 18 G.A. Wheaton 19 G.A. Wheaton 20 F.E. Herkes
and D.J.
Burton,
and D.J. Burton, and D.J.
Burton,
and J.A.
Headley,
Tetrahedron
Letters,
J. Org. Chem.
>
(1976) 895.
(in press, Spring
1983).
J. Org. Chem., -32 (1967) 1311 and -33
(1968) 1854. 21 D.J.
Burton
22 Unpublished 23 The
Fluorine
Chemistry,
-18 (1981)323.
work of H.W. Tsao and G.A. Lodoen,
University
of Iowa.
salt [Ph3PCFC12]C1-,
our laboratory directly
has been prepared
-via an alternative
by D.G. Cox, but we have been unable
to obtain
route in this salt
from CFC13.
24 This salt was first prepared C. Callis, 5715.
Journal
J. Shoolery
by Van Wazer and co-workers,
and R. Jones,
J.
Amer.
J. Van Wazer,
Chem. Sot., -78 (1956)
357 25 D.J.
Burton,
Daytona
S.W. Hansen,
Beach,
Florida,
26 R.W. Vander Haar,
Burton,
D.J.
(1972) 381; unpublished 27 M.J. Van Hamme and D.J. 28 (E)- or @)-
and G.S. Shaw, 6th Winter
February
Conference,
and D.G. Naae, J. Fluorine
Chem.,
j_
work of RWVH. Burton,
stereochemistry
= 22-26 Hz and JCF
Fluorine
1983.
J. Fluorine
is readily
F(trans)
Chemistry,
assignable
-13 (1979) 407. F(cis)
based on JCF 3'
= 11-14 Hz.
3' 29 J.L.
Hahnfeld
30 Unpublished national
and D.J.
Burton,
Tetrahedron
work of S.W. Hansen,
Symposium
1982, Abstract
of Fluorine
I-31; Journal
University
Chemistry,
Fluorine
31 M.J. Van Hamme and D.J. Burton,
Letters,
of Iowa; cf. 10th Inter-
Vancouver,
Chemistry,
Journal
(1975) 773.
Canada,
August
-21 (1982) 18.
Organometallic
Chemistry,
-169
(1979) 123. 32 D.J.
Burton
Chem.,
and H.C. Krutzsch,
Tetrahedron
Letters,
(1968) 71: J.
33 Evidence carbene
for ylide
dissociation
was originally
D. Thesis).
Chemistry, Fluorine
Vancouver,
by D.G. Naae
appears
-21 (1982) 71.
McKelvie,
(University
to be general
of Iowa, Ph.
for various types ofdi-
outlined
+
of [Bu3PCF2Br]Br-
previously
for the formation
35 This ketone does not react directly 36 F. Ramirez,
and difluoro-
cf. 10th International Symposium of Fluorine Canada, August 1982, Abstract O-53; Journal
that the formation
mechanism
phosphine
ylides;
Chemistry,
34 We assume
into tertiary
discovered
Such behavior
fluoromethylene
J.F. Pilot,
J. Amer.
the carbene
of (I).
with Bu3P as C6H5COCF3
N.B. Desai, C.P. Smith,
Chem. SOC.,
follows
B. Hansen,
does [14]. and N.
(1967) 6273.
g,
37 Unpublished
work of D.G. Cox, University
38 D.J. Burton
and D.G. Cox, J. Amer. Chem. Sot. (in press, Spring
39 D.J.
and D.G. Naae, J. Amer.
Burton
40 H.S. Kesling
and D.J.
41 D.J. Burton,
Y. Inouye,
(1980)
Org.
35 (1970) 2125.
3980.
Burton,
1983).
Chem. Sot., 95 (1973) 8467.
Tetrahedron
and J.A.
of Iowa.
Headley,
Letter:
(1975) 3355.
J. Amer.
Chem. Sot., -102
January
8, 1983
; accepted:
PREPARATION AND SYNTHETIC PHOSPHONIUM
11, 1983
January
UTILITY
339
OF FLUORINATED
SALTS AND PHOSPHORANIUM
SALTS
PHOSPHONIUM
SALTS,
BIS-
rli
DONALD J. BURTON
Department
of Chemistry,
University
of Iowa, Iowa City,
Iowa 52242
(U.S.A.)
SUMMARY
The reaction
of tertiary
rapid and high yield
synthesis
salts, -bis-phosphonium ful precursors Examples
phosphines of various
types of fluorinated
salts and phosphoranium
to fluorine-containing
of the preparation,
of these novel
with fluorohalomethanes
reagents
salts.
ylides,
mechanism
a
phosphonium
These salts are use-
carbenes
of formation,
provides
and methide
and synthetic
ions. utility
is described.
INTRODUCTION
The Wittig paration
Reaction
of olefins
is one of the most widely
and substituted
one to select
the substituents
proper choice
of ylide
attached
and aldehyde
allows one to unequivocally
predict
used routes
olefin derivatives. to the olefinic
or ketone,
and more
the position
for the pre-
It readily center
permits
via the
importantly
of the alkene
it
center
in
the final product.
R ~-CR'R' 3
+
R3C(0)R4
For the normal Wittig
R3P0
+
R1R2C=CR3R4
route to be successful
plished;
(1) successful
tertiary
phosphine
removal
---t
alkylation
to produce
of an a-hydrogen
the required
phosphonium
from the phosphonium
thus, at least one a-hydrogen
two key steps must be accom-
of the appropriate
must be present
substrate salt;
salt to produce
by the
(2) selective the ylide
in the phosphonium
-
salt pre-
cursor.
0022-1139/83/$3.00
0 Elsevier Sequoia/Printed
in The Netherlands
340 R3P:
R'R*CHX
+
[R LHR'R*]X3
+
Several years potentially
general
However,
+
-+
and useful
CHF2X
phosphines;
and its abstraction
salt; an approach ylide;
that avoided
an
alternative chemistry
in situ -reactive
or generated
focus attention will detail
can be made.
the extensions
Although ium salts
work
we have prepared
[2], for illustrative
[(R~N)~&Fc~~]c~are representative fluorohalomethyl
capture
of the ylide
or
produced
the ylide
of the mechanistic
It will
of these reagents Indeed,
and
it's only
approach
to these
of the initial mechanistic salts and phosphoranium
of fluorohalomethyl
[R3$CF2Br]Br-,
for discussion and synthetic
salt chemistry
in its
process.
in these areas will be briefly
purposes
an
some of the mechanistic
intelligent
a wide variety
have been selected
phosphonium
the
of several
to bis-phosphonium
and some of our preliminary
to produce
interpretations.
that a designed
an
reactions
in situ
Further extrapolations
[R3P-CF2],
failed.
of the phosphonium
stabilization;or
understands)
by
was not very+ac_idic
to solve these problems.
utility
reasons:
alkylated
was needed that avoided
via a dissociative
(or hopefully
[Base H]'X-
at pregeneration
that either mimicked
our approach
on the synthetic
steps in these reactions
suggested
of ylide
some of our mechanistic
when one understands
ylides
permitted
the ylide
and ylide.
Wittig
(c) the ylide
in the preparation
intermediate
This report outlines
or messy;
proton abstraction
mechanism
Our
for the following
in the [R3PCF2~]X-
that an approach
and a route that either
provided
success
and all attempts
reaction
+
CR~&F~]
were not easily or cleanly
(b) the hydrogen
obvious
as a
olefins
above for a "normal"
base_
by base was difficult
Thus, it became
olefins.
of the difluoromethylene
outlined
derivatives
SN2 type of displacement
Reaction
is:
met with little
was found to be very unstable
the Wittig
of difluoromethylene
precursors
[R3&~2~]~-
this approach
[Base H]+X-
route to fluoromethylene
strategy
+
+
to investigate
likely approach
(a) the difluoromethane tertiary
[R3LR'R*]
on the preparation
the normal
the most
R3P:
Base
of the required
If one follows reagent,
[R LHR'R*]X3
ago we decided
initial work focused the preparation
+
[3].
ideas
salts,
reviewed. phosphon-
[Ph36CFBr2]Br-,
and
in this paper as they types encountered
in
341 RESULTS
AND DISCUSSION
Bromodifluoromethylphosphonium In contrast phosphine reacted
literature
reports
on the failure
of triphenyl-
to react with CF31 and CFC13, we found that triphenylphosphine
readily with CF2Br2
essentially glyme
to earlier
salts
a quantitative
+
(usually within
precipitates
CF2Br2
-$
30 seconds)
salt (I)
of the phosphonium
salt (I)
solvents
Ph3P:
in diglyme yield
and can be easily
[Ph3iCF2Br]Br-
isolated
to give
In
[4]. by
4
- lOO%, (I) It is easily
filtration.
proper attention procedures,
it is easily
A similar the analogous
reaction
by water or protic solvents
+
solvents
and Schlenk
but with
transfer
and readily manipulated. with tris-dimethylaminophosphine
phosphonium
(Me2N)3P:
hydrolyzed
to the use of anhydrous
salt (II)
D(;,
CF2Br2
[5].
In contrast
and CF2Br2
to (I),
salt
gives
(II)
is
[(Me2N)3&F2Br]Br(II)
not hydrolyzed OH-.
by water
or protic
solvents,
In fact, this type of solvolytic
types of fluorohalomethyl triphenylphosphonium alcohol;
phosphonium
derivatives
(b) trialkylphosphonium
not by alcohol; by neither
but is hydrolyzed
behavior
salts that we have worked
are readily
hydrolyzed
derivatives
are hydrolyzed
(c) tris-dialkylamino
by aqueous
[6] is characteristic
phosphonium
ofall
with:
(a)
by water and by water
derivatives
but
are hydrolyzed
water nor alcohol.
+ e
[(R2N)3PCF2XlX Mechanism
example
mechanism
salts
[8].
the formation
of a typical
of formation
have proposed
decreasing
[71
ease of hydrolysis
of salt formation
At first glance another
[Ph3&F2X,X-
of (I) and (II)
SN2 displacement
of (I) and (II)
the following
sequence
would appear
type reaction.
is much more complicated, to explain
the formation
to be
However, and we
of these
the
342 +
R3P:
CF2Br2
+
[R3iBr]
+
(positive halogen abstraction)
[CF2Br]-
R = Ph, Me2N
[CF2Br]-z
R3P:
[:CF2]
+
Br-
(carbene
formation)
&i-&2]
(carbene
capture)
+
[:CF2] 3
+
+ +
[R3PBr]
-
[R3PCF2Br]Br-
+
R3P: (positive halogen abstraction)
The key initial
step is abstraction
attack on carbon (CF2Br2)carbene wise formation distinguish
(SN2)-and
may be formed 2 of [CF2X]-
between
electrophilic tertiary halogen
from
or continue
[R3PBr] or CF2Br2 to complete
Evidence
Ph3P:
+
CF2BrI
If the mechanism
(IV).
preferential
[Ill.
proposal
-$&
[Ph3cCF21]Br-
of formation
+
captures
positive
and initiate
is [lo]:
[Ph3&F2Br]I-
(III)
(IV)
2
1
of (I) involved
SN2 attack
that (IV) should be the predominant leaving
as noted above,
The formation
carbene mechanism
pathway The
by the nucleophilic
- which
the salt formation
with this mechanistic
- based on the better However,
simplicity.
captured
ylide
- we cannot
- the stepwise
with CF?BrI
one would anticipate
bromide.
rather than via step-
process.
consistent
(a) Reaction
product
is subsequently
- not
In this case
to carbene
pathway
for operative
to give the phosphonium
the chain
process
by dissociation
or stepwise
scheme merely
difluorocarbene
phosphiye
halogen)
of difluorocarbene.
a concerted
followed
a concerted
is used in the preceding
of Br+ (attack on
formation
[91
of (III)
group ability
the predominant
as the major
of iodide compared product
product
on carbon,
or exclusive to
is (III) - not
is consistent
with the
- since in the initial or final step one would anticipate
abstraction
of the more polarizable
iodinecomparedto
bromine
343 (b)
Reaction
+
Ph3P:
in the presence
CF2Br2
w
H20
of proton donors
[Ph3iCF2H]Br-
+
CF2HBr
55% Since hydrolysis [Ph3&F2H]Br-
involved
of the intermediate
SN2 attack
hydrolysis
of (I) gives only CF,HBr,
can only be explained
and protonation
on CF2Br2,
[12].
of
ylide
formation
If the mechanism
only the methane
of (I)
would be anticipated
prepared
cursors
to the corresponding
reagents
makes these salts suitable difluoromethylene
from (I) or (II)
halogen
from commercially
of (I) and (II)
readily
phosphine
ylide
formation,
as the
of (I) and (II)
The availability
capture
the formation
via cakbene
product.
Ylide reaction
positive
20%
permits -in situ
of the ylide
[R3iCF2Br]Br-
formation
R3P:
e
Abstraction
of the appropriate aldehyde
t[RAP-CF~]
+
or
and attractive
ylides.
by a second equivalent
by the appropriate +
available
preof
of the tertiary ylide
and -in situ
or ketone
+ [R3PBr]Br-
Cl31
R= Ph, Me2N [ ,,;-,,;I
Illustrative given
examples
approach
F2C=C<
+
of the synthetic
comments
applicability
+
on the mechanism
are needed
applicability
of
(I)
and (II) are
of (I)
(a) The reaction
of this reaction
olefins. or (II)
with a second equivalent
equilibrium
reaction
Thus,
is always an excess
there
important Wittig olefins
[13] - with the equilibrium
to consider
reaction readily
of R3P present
this equilibrium
react with tertiary
of this aldehyde
with PhCOCF3
in Table
with(Me2N)3P
[16].
dehalogenation
-far to the left.
ketones
phosphines
[15],
Similarly,
II is due to rapid reaction
this type of [14] and Thus,
in
the low yield of this ketone
can be often circumvented
of the pre-generated
It is
is due to rapid and destructive
with Ph3P.
This problem
of R3P is an
in solution.
when designing
- since some polyfluorinated
I the low yield with C6F5CH0
reactions
and its synthetic
to permit one to get the best results with this
to difluoromethylene
Table
R3P0
I and II.
in Table Several
>c=o
+
phosphonium
via
salt with a metal [15:
344 TABLE
I
2 Ph3P
f
CF2Br2
+
>C=O-$$+
>C=CF
2
+
Ph3PO
+
Ph3PBr2
>c=o
>C=CF
C6H5CHO
C6H5CH=CF2
65
C6F5CHO
C6F5CH=CF2
20
C6H5COCF3
C6H5C(CF3)=CF2
85
C6H,,COCF3
C6H,,C(CF3)=CF2
90
C6H5COC2F5
C,H,C(C,F,)=CF2
82
cH3(CH2)6CH0
CH3(CH2)5CH=CF2
72
m-BrC6H4COCF3 -
m-BrC6H4C(CF3)=CF2
83
C6H5COCH3
C6H5C(CH3)=CF2
TABLE
% yield
2
2
II
2(Me2N)3P
+
CF2Br2
+
bC=O-$
>C=CF
2
+
(Me2N)3P0
+
(Me2N)3PBr2
x=0
>C=CF
C6H5COCH3
C6H5C(CH3)=CF2
81
C6H5COC2H5
C6H5C(C2H5)=CF2
82
(C2H5)2C0
(C2H5)2C=CF2
75
0
0
% yield
2
=CF2
71
(CH3j2C0
(CH~)~C=CF~
60
C6H5COCF3
C6H5C(CF3)=CF2
25
=0
345 (b) The choice of which electrophilicity typical
of the carbonyl
aliphatic
aldehyde
aldehyde
(PhCHO),
successfully activated However,
ylide system to utilize
(PhCOCH3)
ketones
olefin.
and ketones Obviously,
nonproduct.
ylide
[17], all
converted
can be easily because
pared to Ph3P:, the more reactive ployed only with obstinate
reaction
ketones
olefinic
[(Me2N)3P-CF2]
noted above and the enhanced
acid-base
a typical
are successfully
system most aldehydes
yields
However,
I, a
aromatic
to the
Thus, by the proper choice of the ylide
CF2=C< type olefins.
(c) With highly enolizable
in Table
a typical
gives only traces+of
with the more nucleophilic
types of non-activated
Thus,
by the
a_ctivated (trifluoromethyl)
react with [Ph3P-CF2].
ketone
difluoromethylene
problem
component.
[cH~(cH~)~cHo],
and typica!
is dictated
converted
reactivity
ylide
to
of the equilibrium of (Me2N)3P:
system
is generally
comem-
substrates.
substrates,
these basic ylides
(which quenches
the ylide)
undergo
an
and gives poor
of olefin.
[(Me2N)3GCF2]
However,
+
cyclopentanone
successful
formation
type can be readily
+
[(Me2N)&F2H]
+
of difluoromethylene
accomplished
enolate
olefins
by an ylide-carbene
of this
reaction
[18,
191. (d) This route to the difluoromethylene and is not characterized amounts
of fluoride
addition formed
ion.
and fluoride
olefins
avoided
of the isolated
product)
route.
substituted
Similarly,
the HF addition
(Table I) in contrast encountered
this method
yield of olefin
product -via the [4].
derivatives
have been reported
sensitive [Zl].
[20] and salt
olefin
of fluoride-ionisomerization
salt method
of fluoroolefins
Similar
[21] in the acetate
gives only the terminal
to the problems
with the acetate
the preparation
substituted
derivatives
PhCOCF2CF3
For
this ketone gives mainly
route to the ylide
were found with chloro
trifluoromethyl
of the initially
(Table I) gives an excellent
sodium chlorodifluoroacetate results
isomerization
with this approach.
salt route, whereas
via the phosphonium (ss%
is a mild, clean route of any significant
Thus, many of the probl,ems of HF
ion catalyzed
are easily
example,m-SrC6H4COCF3
ylides
by the formation
[20].
Other examples
to fluoride
ion fi
of
346
(e) The reaction
can be applied Ph3P ,m*
EtC(O)(CF2)2C(O)Et
to polyfunctionalized
F2C=$(CF2)2;=CF2 Et
+
derivatives:
enone
Et
6%
50%
[=I
Ph3P m
PhC(O)(CF2)3C(O)Ph
F2C=F(CF2)3F=CF2 2
2
Ph
+
enone
Ph
16%
57%
Dihalofluoromethylphosphonium
Typical
Ph3P:
examples
+
CFBr3
salts
of salts of this type are illustrated
below:
[Ph3&FBr2]BrS
-
(VI t (Me2N)3P:
+
CFC13
d
[(Me2N)3PCFC12]C1 (VT)
With the more polarizable (Ph3P) affords
methane
the phosphonium
with Ph3P to give a phosphonium in the preparation phosphine
must
phosphonium ion pair.
R3P:
salts
+
--t
utilized
of formation
abstraction
of salts of this type
of bromodifluoromethyl-
of positive
halogen
the mechanistic
~R,;;x]cFx,;~,,
[24].
to produce
pathways
an
diverge.
[R~&Fx~]x-
X = Br, Cl
R = Ph, Me2N
CF2x2,
conditions
salt formation
step in the formation
at this juncture
CFX3
Since the methide
to accomplish
- namely,
However,
phosphine
CFC13 does not react
[23]; hence the more halophilic
step in the mechanism
to the initial
the less halophilic However,
salt under the normal
of these materials
be employed
The initial is similar
(CFBr3),
salt (V).
ion produced
it recombines
from CFX3 is longer
with the halophosphonium
attack on the phosphonium
center)
lived than the ion fror
cation
(via nucleophilic
to give the phosphonium
salt.
347 Evidence
consistent
(MIZ~N)~P:
+
with this mechanistic
0r_EtOH
cFci3
of traces Since
between
(VI) is stable
it would
of (VI).
not undergo
the halogen reaction
(Me2N)3P
if (VI)
further
of the methane
between
the methide
cleavage
phosphine
+
CFBr3
+
Similar
(SN2).
of the chain-extended
CF2=CFCF3
tertiary
phosphine
__)
ylides
+
[Ph3&FBr2]Br-
+ [(Me2N)3PCFC12]Br -
Table
III
summarizes
fluoromethylene out stepwise
olefins ylides
CFBr2
[Ph3&FBr]
+
'CF
3
salts with a second mole of
examples Again,
[26]
and
+
(Me2N)3PC12
of the preparation the reaction
of bromo
may be carried
obtained
are readily
The fluorohalo-
are possible.
reagents
[30], zinc [30], or copper
for the preparation
Ph3PBr2
In the case of the bromofluoro-
procedure.
are usually
+
[(Me2N)3&FC1]
via this route. -
olefins
[251
F
bromofluoromethylene
both (E) and (I) isomers
bromofluoromethylene
is electrophilic
(via capture of mechanistic scheme.
/
dehalogenated
are not stereospecific
isomers
[29], Grignard
+
(Me2N)3P:
or -via a one-pot
methylene
useful entry
Ph3P:
+
if the
[27].
some illustrative
olefins
methylene
geometrical
can be further
with is on
olefin
with the proposed
to give the respective
chlorofluoromethylene
experiments
as acompetitive
of dihalofluoromethylphosphonium
(V) and (VI)
Salts
be formed via
Similarly
F'
utility
cannot
- that initial attack
'c=c
Synthetic
is observed.
and the trihalofluoromethane
ion) is again consistent
Ph3P:
to CHFC12.
of a fluoroolefin
the formation
out in the presence
No (VI)
had been formed -via SN2 attack on CFC13,
and not on carbon
tertiary
agent,
is carried
is observed.
lead to the same conclusion
out in the presence
trapping
and CFC13
to both EtOH and H20, the CHFC12 Thus,
CFBr3 and (Me2N)3P
carried
95%
of EtOH or H20. only CHFC12
hydrolysis
is:
CHFC12
H2° When the reaction
interpretation
and where
in w 1:l ratio converted
possible,
[2B].
into vinylic
[30] reagents,
of polyfunctionalized
the
Since these lithium
they provide
a
fluorinederivatives.
348 TABLE
III +
CPh3iCFBr2,Br_
Ph3P
+
>C=O
solvent_*>C=CFBr
+
Ph3PO
+
Ph3PBr2
>c=o
>C=CFBr
% yield
C6H5CHO
C6H5CH=CFBr
70
C6H5COCF3
C6H5C(CF3)=CFBr
97
C6H5CH2COCF3
C6H5CH2C(CF3)=CFBr
59
C6H5COC2F5
C6H5C(C2F5)=CFBr
65
CF3COCF3
(CF3)2C=CFBr
80
C6H5COCH3
C6H5C(CH3)=CFBr
45
C3F7COC3F7
(C3F7)2C=CFBr
79
*Solvents
such as THF, CH3CN,
solubility
of the carbonyl
The phosphine completely
An alternative
of (VI)
to the other
generation
occurs
stabilized
ylide
with zinc metal
[(Me2N)3&FC12]C1-
Zn
solution
of this reagent
+
to the "free" ylide
loses activity cellent
[(Me2N)3i-CFC1].
with typical
examples).
carbonyl
Only highly
+
of a metal-
However,
substrates
enolizable
ZnCl2
The free ylide
this metal-stabilized
(- 1% per day) over one month.
reactivity
illustrative
is -via use dehalo-
[(Me,N),iCFClZnCl]Cl-
[(Me2N)3PCFCl]
life less than l/2 hr. [32], whereas
salts.
is remarkable
IJ t- (VII)
compared
[27] and is
phosphonium
With salt (VI) facile
to give a stable
The stability
+
reported
of these salts, however,
(as noted earlier).
[31].
on the
has been reported
previously
mode of dehalogenation metal
depending
substrate.
dehalogenation
analogous
of an active
CHCl3 were utilized
has a half-
reagent
slowly
(VII) exhibits
(cf. Table
substrates
IV
for
give poor
ex-
349
IV
TABLE
t [(Me2N)SPCFC12]C1-
+
Zn(Cu)
+
THF F
X=0
>C=CFCl
>c=o
>C=CFCl
% yield
C8HSCHO
CSHSCH=CFCl
100
CSHSCOCFS
CEHEC(CFS)=CFCl
100
CEHSCOCHS
CSHSC(CHS)=CFCl
70
CH3(CH2)SCH0
CHS(CH&H=CFCl
0 =o
0
CF3C02CH3
results
- due to protonation
(VII) dissociates
is easily
the preparation
of chlorofluoromethylene
The metal dehalogenation of metal-stabilized laboratories.
phine
Preliminary
(V).
examples
mixture.
converted
Some of our preliminary
and some typical in Table
indicate
by the tertiary
can be readily
of
is storable, of choice
and for
salts and the formation
under active
of several
in the reaction
that are attacked
approach
method.
route of phosphonium
results
that
olefinating
olefins.
aspect of this mode of approach
is present
is the actual
in high yields,
re-
we assume
scaled up, it is the method
is currently
and will be the subject
strates ylide
ylides
90
Since the stereochemical
which
prepared
can be readily
important
18
(VII) or the 'free' ylide,
to the 'free' ylide,
(VII)
Since
of the ylide.
with either
its preparation
method
=CFCl
CFSC(OCHS)=CFCl
sults are identical
species.
100
investigation
in our
that it is a generally
useful
reports
Thus, carbonyl phosphine
to olefins
results
the utility
in the near future.
is that -no excess
tertiary
One phos_
or olefinic
sub-
and fail in the normal via this alternative -
with salt (I) have been reported of this approach
are illustrated
350 TABLE
V t
RCOR'
Metal
(M)
+
[Ph3&FpBr]Br-
+
&RR~c=cF~
MBr2
+
Ph3PO
RCOR'
RR'C=CF2
Cd
Hg
Ph3Pa
C6H5C(0)CF2C1
C6H$(CF2Cl)=CF2
76
21
25
C6F5C(0)CF3
C6F5C(CF3)=CF2
83
71
0
C6F5CH0
C6F5CH=CF2
62
41
20
C6F5C(0)CF2Cl
C6F5C(CF2C1)=CF2
72
64
0
(a) Yield of olefin when Ph3P was used as the dehalogenation
-Bis-phosphonium
Although (VI)
salts
our work with phosphonium
continues,
to other
we have recently
interesting
This work
and novel
is of recent
vintage
with the fluorohalomethyl
salts such as (I), (II), (V), and
begun to examine
and obviously
phosphonium
salts.
However,
and synthetic
outline
some of the interesting
features
the mechanistic
difluoromethylene
ylide
second equivalent
of the tertiary
equilibrium
we would like to
ideas on this subject
of these reactions
and to
that are being
involved
scheme
abstraction phosphine
for the preparation of Br+ from to establish
of the
(I) or (II) -via a the following
[13].
[R3&F2Br]Br‘
+
R3P:
the importance
cation
to donate
,k
[R3iBr]B;
+
[R3&F2]
of this equ ilibrium is the ability of the I BrT back to the ylide - thus preventing rapid
dissociation
[33] and decomposition
to the ylide
which
been noted.
intermediates. as the work
in our laboratory.
As noted earlier
[R3PBr]
synthetic
not as complete
some of our mechanistic
We $elieve
these salts as precursors
phosphorus-fluorine
present
investigated
reagent.
do not involve
of the ylide. R3PBr2,
Indeed,
no stabilization
in other routes of the ylide
has
351 In additionto suggests ylide
recapture
an alternative
on the phosphorus
,3&F,
of Br+bythe
ylide,
the above equilibrium
mode of reaztion -namely, atom of [R3PBr]
+
[R3iBr]Br-
nucleophilic
attack
to give a fi-phosphonium
also
by the
salt.
tt [R3PCF2PR3]Br-
e
-bis-phosphonium
salt
(VIII) When R = Ph or Me2N, little b&-phosphonium [lo].
However,
observed,
salt formation
when R = alkyl, -bis-phosphonium
and the -bis-phosphonium
is observed
salt formation
salt can be easily
is readily
and rapidly
formed
in
high yield.
2 Bu3P:
+
CF2Br2
Again,
the key mechanistic
1341.
Does the step involve
by a second equivalent
[Bu3&F2Br]Br‘
[Bu3&FZiBu3]2
e
question
is the second step in this sequence
SN2 attack on carbon or abstraction
of the tertiary
+
Br-
of halogen
phosphine?
Bu3P SN2 \
[Bu3~CF2~Bu3]2
Br-
/ tBu3PCF2
+
When the reaction presence
t of [Bu3PCF2Br]Br-
of PhCH2COCF3
phosphonium the positive capture
+ [Bu3PBr]Br
salt were observed. halogen
of the ylide
with Bu3P is carried
[35], the difluoromethylene
abstraction
These products mechanism
and the reduced
of any SN2 type reactions
[Bu3&F2Br]Br-
t
PhCH2COCF3
and the reduced
are only consistent
- the olefin
ketone.
Thus,
capture
again we note the
in these processes. Bu3P H
CF2=;CH2Ph
+
CBu3&F2HlBr‘
cF3 50%
with
is formed via
salt is formed -via proton
from the enol of the benzyltrifluoromethyl absence
out in the
olefin
50%
352 The b&-phosphonium interesting
mixed
salt preparation
opens up many new routes to
salts as well as mixed valence
in the two illustrative
[Et3LFZBr]Br-
+
species,
as shown below
examples.
Bu3P:
__t
[Et3&FZiBu3]
2 Br-
[lOI
70%
[Bu3&F2Br]Br-
A detailed
+
(Et0)3P:
investigation
exciting
Phosphoranium
[Bu&F2P(0)(OEt),]Br-
+
EtBr
of the scope of these and other -bis Species
Our preliminary
now in progress. anticipate
w
work suggests
Cl01 iS
that we can undoubtedly
and novel results.
salts
Our preliminary previous related
work with -bis-phosphonium salts outlined in the led us to explore related work with salts such as (V) and
section
derivatives.
anticipate
Again
(based on the earlier
that nucleophilic
the bromophosphonium
cation would
[Ph3iCFBrp]Br-
+
work),
one might
attack of the bromofluoromethylene
Ph3P:
lead to a -bis-phosphonium
e
[Ph,&;Br]
+
ylide on
salt.
[Ph3iBr]Br-
1 [Ph3&FBr~Ph3]2
Br-
(IX) There
is, however,
salt (IX) there carbon
one important
atom - whereas
abstracted
phosphine
is added,
carbon perhaps
atom.
(IX)
(VIII)
present
ZBr-
+
Ph3P:
-+
Thus,
this reactive
to give the fluorine-containing
CPh3&FBriPh3]
between
halogen
In
easy abstraction
if another bromine
phosphoranium +- + [Ph3PCFPPh3]Br(X)
and (IX).
on the methylene
in (VIII) one would not anticipate
of Ff from the difluoromethylene of tertiary
difference
is still a polarizable
salt,
+
equivalent
can be
(X) [%I.
Ph3PBr2
353
In fact, one finds that the bromine
in (IX) is much more reactive
bromine
in (V) and even with a deficiency
of tertiary
rapidly
formed from (V) in an appropriate
solvent
With this information fluorine-containing procedure
in hand, the obvious
questions
salts be directly
from fluorohalomethanes?
Can the cheaper
these questions
Fortunately
is affirmative
CFC13 can be used with trialkyl
3 Ph3P:
+
+
CFBr3
for the synthetic
as outlined
below
phosphines,
than the (X) is
[37].
phosphoranium
these preparations?
phosphine,
are:
can
formed via a one-pot CFC13 be utilized in chemist,
[37,38].
the answer Either
to
CFBr3 or
such as Bu3P; CFC13 does not
[Ph3iCFzPh3]8r-
+
Ph3PBrp i
+
Bu3PBr2 4
+
Bu3PC12
90%
+- + +
3 Bu3P:
CFBr3
---t
[Bu3PCFPBu3]Br80-90%
+
3 Bu3P:
CFC13
d
[Bu~&FLJ~]C~-
95%
react with Ph3P as noted earlier. ium salts are rapid, able commercial
clean,
chemicals.
use in the preparation A unique
fluorides.
R &R1R2 3
ylides
+
are treated
R3C(0)X
that the fluorine-containing reaction phonium olefin.
with E-acyl salt.
yields
from readily
avail-
find extensive
compounds. has already
of phosphoranium
to the normal
to form the phosphoran-
in our estimation,
of these reagents reaction
- namely,
In contrast
phosphonium
and give excellent They will,
of fluorinated
application
our laboratory
These reactions
acylation
been discovered
reaction
with acyl halides,
in
salts with E-acyl observed
when
we have discovered
[R ~cR'R~C(~)R~]X3
-
phosphoranium
fluorides
Base hydrolysis
salts rapidly
to give stereospecifically give stereospecifically
undergo
a Wittig
the (I)-phos-
the (E)-1-hydro-E-
354
+
[Bu3&FiBu33x+ RFC(O)F
+
B"3p\
C=C
F'
,F 'R
X-
+
Bu3P0
F
(Z_)-phosphonium salt
I
H
H20/0H-
\CJF F' ' RF (E)-l-hydro-E-olefin . Table
(VI) gives
of fluoroolefins for several reaction
directly
reasons:
(c) the olefin
of these systems full details
TABLE
from acyl fluorides.
(d) the product
isomer olefins
further -via conventional be reported
(b) the
as only the (r)-
in at least some of the can be readily metallated
is currently
A detailed in progress
study and
in the future.
VI
+- + [BU~PCFPBU~]X-
is attractive
salt need not be
chemistry.
systems
of preparation
available;
stereospecifically
less-stable
as well as related
will
The method
are readily
the ($)-phosphonium
is obtained
the thermodynamically
[29] and elaborated
of this novel method
(a) all precursors
(RF = CF3, C2F5);
cases
examples
is a one-pot procedure-
isolated; isomer-
illustrative
1) RFC(0)F
H +
2) NaOH/H20
1
/F
F,C=c\ RF (E)-olefin
RF
(E)-olefin
% yield
cF3
CF3CF=CFH
45
CF3CF2
CF3CF2CF=CFH
62
CF3CF2CF2
CF3CF2CF2CF=CFH
52
CF2Cl
CF2C1CF=CFH
50
CH302CCF2
CH302CCF2CF=CFH
20
CF3(CF2)20CFCF3
CF,(CF,),OCF(CF,)CF=CFH
49
355 In sunmary, intermediates olefins
these easily
via the nucleophilic
the generation
reagents
[25,41].
containing
reaction
difluorocarbene. taining
transfer
rather
ylides;
agents
intermediates
derivatives
for
[39]; they serve as
[40] as well as chain-extension
the key reactions
are either
has already of fluorine
of these reagents
reaction
they are also useful
difluorocarbene
than attack on carbon,
to the preparation
development
are useful
types of fluoromethylene
are halogen
and the key fluorine-
fluorohalo
The use of these interesting
phosphorus
approaches
phosphonium
Mechanistically,
processes
materials
of various
of the electrophilic
useful fluorohalomethyl
abstraction
prepared
for the preparation
methide
ions or
and novel fluorine-con-
provided
some new synthetic
compounds,
and the further
has a promising
and bright
future.
ACKNOWLEDGEMENT
I would write
like to thank Professor
this overview
extended
of our work
to the National
Scientific
Research
least,
co-workers,
and interesting
Foundation
I would
whose
only for their excellent zest for chemistry
in this area.
Science
who have generously
Last, but by no means my excellent
D.W.A. Sharp for the invitation Our sincere
skills,
of
our work in this field.
like to express
names are included
technical
thanks are also
and the Air Force Office
supported
that they have provided
to
my sincere
thanks
in the references,
but also for the enthusiasm in making
our laboratory
to
not and
a fun
place.
NOTES AND REFERENCES
Taken
in part from a lecture
Symposium
presented
of FluorineChemistry,
O-5; Journal
Fluorine
M.J. Van Hamme, Resonance,
D.J.
Chemistry, Burton,
at the 10th International
Vancouver,
Canada, August
1982, Abstract
-21 (1982) 47.
and P.E. Greenlimb,
Organic
Magnetic
-11 (1978) 275.
cf. to V.V. Tyuleneva, E.M. Rokhlin, and I.L. Knunyants, Russian Chemical Reviews, -50 (1981) 280 for an excellent review of fluorinecontaining Unpublished Journal
halogenomethylene
work of D.G. Naae; cf. also D.G. Naae and D.J. Burton,
of Fluorine
D.G. Naae and D.J. Unpublished
ylides.
Chemistry Burton,
L-971)
Synthetic
work in this laboratory.
123. Communications,
2 (1973) 197.
356 7 The solvolytic period
behavior
alcohol
may result
ACS Bicentenial Abstraction
Daytona
Symposium,
Beach,
Florida,
may capture
whichever
moiety
of even the less reactive
Phosphonium
Salts'
New York, April 1976,
presented February,
positive
donates
over
salts.
presented
'Positive
at the
Halogen
Containing
at the 5th Winter
FluorineConference,
1981.
halogen
a
to water of
- The Key to Phosphorus-Fluorine
Intermediates'
9 The ylide
hydrolysis
(days) of exposure
of Halogenated
Reactions
Synthetic
periods
in slow hydrolysis
'Chemistry
8 Lectures,
here refers to significant
Prolonged
of hours.
+ either
from [R3PBr] or CF2Br2
Br+ does not change the overall
-
mechanistic
interpretation. 10 Unpublished 11 Control undergo
halogen
reaction 12 Control CF2HBr
work of H.S. Kesling,
experiments
exchange
conditions
that
of Iowa. and/or
(III)
at the halodifluoromethyl
(IV)
carbon
do not
under the
used [lo].
experiments+have
established
to give [Ph3PCF2H]Br-
(1975) 3789 for discussion F.E. Herkes,
that Ph3P does not react with
under the reaction
13 cf. D.G. Naae, H.S. Kesling,
14 D.J. Burton,
University
have established
and D.J. Burton,
of the reversible
conditions
Tetrahedron equilibrium
and K.J. Klabunde,
J. Amer.
[lo]. Letters, in this step.
Chem. Sot., 88
(1966) 5042. 15 D.J.
Burton,
and D.G. Naae, J. Fluorine
H.S. Kesling,
Chemistry,
-18
(1981) 293. 16 F. Ramirez,
C.P. Smith,
and S. Meyerson,
Tetrahedron
Letters,
(1964)
3651. 17 The irder of nucleophilicity
of these ylides
is [Me2N)3i-tF2]
.
[Ph3P-CF2]. 18 G.A. Wheaton 19 G.A. Wheaton 20 F.E. Herkes
and D.J.
Burton,
and D.J. Burton, and D.J.
Burton,
and J.A.
Headley,
Tetrahedron
Letters,
J. Org. Chem.
>
(1976) 895.
(in press, Spring
1983).
J. Org. Chem., -32 (1967) 1311 and -33
(1968) 1854. 21 D.J.
Burton
22 Unpublished 23 The
Fluorine
Chemistry,
-18 (1981)323.
work of H.W. Tsao and G.A. Lodoen,
University
of Iowa.
salt [Ph3PCFC12]C1-,
our laboratory directly
has been prepared
-via an alternative
by D.G. Cox, but we have been unable
to obtain
route in this salt
from CFC13.
24 This salt was first prepared C. Callis, 5715.
Journal
J. Shoolery
by Van Wazer and co-workers,
and R. Jones,
J.
Amer.
J. Van Wazer,
Chem. Sot., -78 (1956)
357 25 D.J.
Burton,
Daytona
S.W. Hansen,
Beach,
Florida,
26 R.W. Vander Haar,
Burton,
D.J.
(1972) 381; unpublished 27 M.J. Van Hamme and D.J. 28 (E)- or @)-
and G.S. Shaw, 6th Winter
February
Conference,
and D.G. Naae, J. Fluorine
Chem.,
j_
work of RWVH. Burton,
stereochemistry
= 22-26 Hz and JCF
Fluorine
1983.
J. Fluorine
is readily
F(trans)
Chemistry,
assignable
-13 (1979) 407. F(cis)
based on JCF 3'
= 11-14 Hz.
3' 29 J.L.
Hahnfeld
30 Unpublished national
and D.J.
Burton,
Tetrahedron
work of S.W. Hansen,
Symposium
1982, Abstract
of Fluorine
I-31; Journal
University
Chemistry,
Fluorine
31 M.J. Van Hamme and D.J. Burton,
Letters,
of Iowa; cf. 10th Inter-
Vancouver,
Chemistry,
Journal
(1975) 773.
Canada,
August
-21 (1982) 18.
Organometallic
Chemistry,
-169
(1979) 123. 32 D.J.
Burton
Chem.,
and H.C. Krutzsch,
Tetrahedron
Letters,
(1968) 71: J.
33 Evidence carbene
for ylide
dissociation
was originally
D. Thesis).
Chemistry, Fluorine
Vancouver,
by D.G. Naae
appears
-21 (1982) 71.
McKelvie,
(University
to be general
of Iowa, Ph.
for various types ofdi-
outlined
+
of [Bu3PCF2Br]Br-
previously
for the formation
35 This ketone does not react directly 36 F. Ramirez,
and difluoro-
cf. 10th International Symposium of Fluorine Canada, August 1982, Abstract O-53; Journal
that the formation
mechanism
phosphine
ylides;
Chemistry,
34 We assume
into tertiary
discovered
Such behavior
fluoromethylene
J.F. Pilot,
J. Amer.
the carbene
of (I).
with Bu3P as C6H5COCF3
N.B. Desai, C.P. Smith,
Chem. SOC.,
follows
B. Hansen,
does [14]. and N.
(1967) 6273.
g,
37 Unpublished
work of D.G. Cox, University
38 D.J. Burton
and D.G. Cox, J. Amer. Chem. Sot. (in press, Spring
39 D.J.
and D.G. Naae, J. Amer.
Burton
40 H.S. Kesling
and D.J.
41 D.J. Burton,
Y. Inouye,
(1980)
Org.
35 (1970) 2125.
3980.
Burton,
1983).
Chem. Sot., 95 (1973) 8467.
Tetrahedron
and J.A.
of Iowa.
Headley,
Letter:
(1975) 3355.
J. Amer.
Chem. Sot., -102