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Mild protection and deprotection of alcohols as ter-butyl ethers in the field of pheromone synthesis
Tetrahedron Printed in
Letters,Vol.29,No.24,pp Great Sritain
MILD
PRORATION
2951-2954,1988
AND B~~R~T~~T~ON IN
THE FIELD
Laboratoire Universiti
reaction turn,
with
P. et M. Curie,
conditions
During
to
conjugated
our
studies
carbocupration bearing
in
t-butyl
protection
can
be
reagents,
mainly
because
chelation
of
metal
the
ethereal
solvents
prepared
in Et20
not at
all
These
advantages
in
of
the
of
its
scale
reactions
of
of
the
as
the
H-15.
t-B&y1
by
are,
in
ethers Under
we
these
group the
required,
mild
the
which
ether
ones
our ether
Grignard
efficiently
any
functionality
and Grignard
non-functionalized
for
t-butyl and
impedes
t-butyl
the
reagents,
protection, that
organo~ith~um
organolithium
for
or Grignard
appropriate realized
whydroxy of
ethers
nor isomerized.
most
t-butyl
05
as t-butyl
solvent.
synthesis,
also
oxygen
ru-t-butoxy
t-butoxy
the
resin
and
we have
to these
found
of insect
with
bearing and
isobutene
reagents
and their
(in can
be
reactivity
is
of remaining
alcohol
point of view,
and their
presence
formation
of an organo~~th~um
The following
The
these
is often
compounds
however, after
problems,
limited
solutions
by 4
reactian
the
difficulties
. We report
herein
the
which we have used for many
and,
syntheses,
of
an acid
1s quantitative
the
with
case
the
of alcohol
responsible
or a Grignard prepared
for
usual
are the
2951
we
aqueaus
problems
have
acid
to remove encountered
:
H-15o,
been used for the protection
and
difficult
manner
as t-butyf
: Amberlyst
for the preparation
reagent. in this
protected
are
catalyst
has already
in patents,
reaction
traces
have been
presence
This catalyst ethers7,
as is
practical
are,
removal
pheromones5.
in the
-S03H groups.
alcohols'.
its
for our organometalfic
as tetrahydropyranyl
from alkenes
group
introduction
syntheses
by reaction
of alcohols
traces
Thus
exactly
The c&rii-halohydrins, required
an acid
bulk
we
Cidex
of organulith~um
The
fact,
Paris
Et22
pheromone amounts
or Mg) by the
of course).
solvent,
most
in
destroyed
functionality.
in
(Li
insect
In
F-75252
45
are protected
FeC13
neither
large
ether’.
useful
solutions
of our large
ethers
of
tour
: Amberlyst
10%
ETHERS
impaired3.
encountered practical
field
tt-hydroxy
the
catalyst
are
of alkynes’,
Jussieu
alcohols
and
.OO
Colin
5.
des Organo-elements,
4 place
acid AcaO
systems
the
reaction
was
an by
dienic
a protected
purpose,
and
acetates
AS TER-BUTYL
f
SYNTHESIS
Gardette,
and W-acetylenic
isobutene
cleaved
) M.
de Chimie
- a,er-ttalohydrins
db.&xac.t
OF ALCOHOLS
OF PHEROMONE
A. Alex&is*
0040-4039/88 $3.00 Pergamon Press plc
not
of ethers
detected
catalysts4.
any
From
a
by distillation9, in
initiating
the
2952
Arsberlyst
R-OH
+
H-15
R-O-t-Bu
+
hexane
===c
A
LAO t
HCGC-FH-Pr 0
A
The
Cl
deprotection
X = Cl,
step
for
was
the
Br,
+
I
n = 3,4,6,8,10
studied
reaction T-2
methods
X-(CH2)n-0
+
n = 1, 2, 3
%
carbocupration known
HC:C-(Ct$)n-0
HCZC-CH2-:H-BU
.
The
removal
of
mainly
two
on
the
following
the
t-butoxy
olefinic
compounds
4,lO
group
products were
obtained
used
to
test
after the
the
various
.
Me
(CH214-0 +
-A The
first
one
functionality favorable system whe
one
although that the of
the
of
the
destruction
diethyl
the
Lewis since
ethylenic
we tried
compounds
O.leq.,
Although,
under
where
hand
similar
cyclisation
the
second
and
is quite
11 ,
we
noticed
t-butoxy
group
ether,
they
may these
;
of the of the
-A and -B.
acid
system
of FeC13,
structurally
position other
modification
and
satisfactory
bond
to
to
one
E
a
isobutene
of
an
tetrahydropyran
possess
representative
and
the
a
Z,Z
kind
oxygen
ring
is
conjugated
of
insect
a
diene
pheromones
prepared5.
complete
a complete
Ac20
a
the
isomerlsation
cleavage
sensitive
double
at On
the methods
partially
the
to
already
all
a
placed
prone
for
has
process.
have
Among
-A
lnstead as
the
tetrahydrofuran, be
increased
new
to
conditions,
FeC13
reactlon on the 0.3 the
eq.
system
allow,
as solvent,
solvent.
of
one
or dienic
conditions
of Ac20
12 system was the fastest 3 minute at room temperature),
Ac20/FeCl
than
monoethylenic
Et20,
down
the
(less
reaction
character
slow
that
The
;
role
methylene
rate
without
other
hand,
in
the
reaction
cases
takes
was
now,
we use of
occuring.
a mild only
Et20
polymerises
five
on eq. mask
are
not
destructlon
of
readily.
hours,
found
to
pentane
the
secondary
several
to
probably,
or
preventing
of
three
is,
chloride
We
deprotection
The
t-butoxy instead
amount ethers. of
less
2953
than one minute, acetates,
we were able,
now,
without isomerisation
to
obtain,
in
high
of any of the tested
yield
dienes
following
the
,
or enynes
14
desired
:
Et20 + 3-5eq. AcZO +
R-O
O.l-0.3eq.
FeC13
A
R -0Ac
+2OT
+
2-15 h Me
Me
===c (CH~)~-~AC
IA
II = 6, 8, 10
(CH21n-OAC
Ety(CH -0Ac 26)
Perk 0
0
Pr
OAc
OAc
To a aoh(utLon UL t-buk& Ac20
i5 m! J ,
i%en
4a*curated
aqueou4
The nvW
ieP04
and ihe o~puc pwufced
elilen
anfqdmit4
i 70 nanoli F-etij
Z-75 houn4 untc-lno
A2mpe/ia_tune
Pr
I/
4oh5un ~4
of
i 250 4.xkzntixy
anh~(lzOU5
.in
rngi.
The
dwik
mahncd
I25mLl
NayP04
~4
bg &4tdutitcon
v/i
150 m4.J ane
b~wn
cd
Ieff
4o&&i.un
M
4ti/red
~cutioL
Lq
TLC
c4
extiacted.
tiue
oven Mg_Y04, .then concentn&ed.
duwmatopuph~.
iheyce.Ldo/Y Me
5
ducce44lvdg
uddedandthp.nux.tu.e LA
f&tuned off, the aqueuu4 layen
pka4e4 ane dued
Et20
(CH~)~-OAC’
w&h
added at
*IL
4.i1.4n~ed &en
worn
~LPCI. A 3 ti.
fan (50
dl
The dunk ncsudue ~4
,cxu.~fiiLeu makvu-ui
~4
u~uuAly
W-95%. Since, that its
now, the t-butoxy
protecting
use in pheromone synthesis,
We especially
organometallic functionality.
recommand it reagent
is
in all
group can be easily and also the cases
elsewhere,
and mildly
where the formation
hampered by the presence
of
removed,
we believe
should not be anymore restricted. or the reactivity
a classically
protected
of an alcohol
J. Normant,
A. Alexakis,
A. Alexakis, There
are
and
M. Gardette,
several
reactivity
Grignard T.W.
in
the
(1981) Tetrahedron
:
litterature
protected
acetal
-41
of
(OTHP,
5887
(1985)
diminished
OEE,
yields
OMEM,
in
etc...)
the
preparation
organolithium
and
reagents.
Greene
in "Protective
Commercially
There
are
deal
with
the
of patents
synthesis
Imaizumi,
Y.
203
Aldrich,
M. Orena, on
Fujiwara
1981 40
2741
(1984)
etc...
S. Sandri
:
topic,
from
terbutyl
Sekiu
:
Wiley,
Tetrahedron
:
(1987)
Fluka,
this
of methyl
Synthesis",
J. Normant
Chimique
from
G. Cardillo, dozens
in Organic
A. Alexakis,
L'Actualiti
:
available
Bongini,
groups
N. Jabri,
b/ A. Alexakis
a/ M.
841
J. Normant
reports of
a/ M. Gardette,
A.
Synthesis
Synthesis the
ether,
Gakkaishi
618
(1979)
petroleum
industry.
an antiknock -27
:
356
additive.
(1984).
C.A.
Most
of
them
See
for
ex.:
101
170.350k
(1984) b/ W.
Weier,
220.342
W.
g
Webers,
Dettmer
D.
Ger.
:
Offen
DE
322,
3,
753
(1985).
C.A.
102
P
121.810
s
(1985)
c/ G. Trevale,
G.F.
Buzzi
Braz.
:
Pedido
PI
BR
8205,
855
(1983).
C.A.
-99
P
(1983) These
traces
procedure
of alcohol
is not
convenient
a/ R.L.
Burwell
b/ M.V.
Bhatt,
S.U.
A
account
of
full
Universite
Jr
a/ E. Knoevenagel
c/ B. Ganem, d/ R.S.
eq.
(ROAC)
is
the
Most
(Received
Small
D.S.
402
Jr
are
:
or a Pd"
has
in the in
90-95%
were
France
have
Chem.
our
this
moles)
is
Chem. 39
reported
new
134
3728
17 1749
in
M.
Gardette's
thesis,
most
on the
other
51
(1932)
(1974)
(1987)
reaction
the
conditions
the
sensitive
dienic
hand,
not
the
does
alcohol
cleavage
systems
react
(ROH),
in
to
are Et20
but
acetate
partially
;
again
in
CH2C12
the
most
destroyed.
obtained
assisted
However,
(1983)
tried
hydrolysis,
by cleavage
coupling
reaction.
immediately
after
of the The
crude yield
t-butoxy of the
ethers
cleavage
after reaction
range.
to be quenched
formation
249
Comm.
under
are
Si02.
(1954)
J. Prakt.
:
However,
systems
(I-5
on
(1914)
Synth.
after
chromatography
1983
J. Org.
chloroformate,
compounds
we
133
:
used
scale
Synthesis
Paris,
Watt
affords,
is in the
results
Ann.
by flash
-54 615
methods
Curie,
ethylenic
reaction
:
Ethyl
of these
itself
large
faster.
carbocupration
The
on Rev.
even
reaction
sensitive
removed
H. Maier-Htiser
of AcCl
destroyed.
be
Kulkarni the
:
V.R.
Gross,
If two
Chem.
:
P. et M.
b/ H. Meerwein,
may
of enol 26
acetates.
February
1988)
completion.
Prolonged
reaction
time
a
Letters,Vol.29,No.24,pp Great Sritain
MILD
PRORATION
2951-2954,1988
AND B~~R~T~~T~ON IN
THE FIELD
Laboratoire Universiti
reaction turn,
with
P. et M. Curie,
conditions
During
to
conjugated
our
studies
carbocupration bearing
in
t-butyl
protection
can
be
reagents,
mainly
because
chelation
of
metal
the
ethereal
solvents
prepared
in Et20
not at
all
These
advantages
in
of
the
of
its
scale
reactions
of
of
the
as
the
H-15.
t-B&y1
by
are,
in
ethers Under
we
these
group the
required,
mild
the
which
ether
ones
our ether
Grignard
efficiently
any
functionality
and Grignard
non-functionalized
for
t-butyl and
impedes
t-butyl
the
reagents,
protection, that
organo~ith~um
organolithium
for
or Grignard
appropriate realized
whydroxy of
ethers
nor isomerized.
most
t-butyl
05
as t-butyl
solvent.
synthesis,
also
oxygen
ru-t-butoxy
t-butoxy
the
resin
and
we have
to these
found
of insect
with
bearing and
isobutene
reagents
and their
(in can
be
reactivity
is
of remaining
alcohol
point of view,
and their
presence
formation
of an organo~~th~um
The following
The
these
is often
compounds
however, after
problems,
limited
solutions
by 4
reactian
the
difficulties
. We report
herein
the
which we have used for many
and,
syntheses,
of
an acid
1s quantitative
the
with
case
the
of alcohol
responsible
or a Grignard prepared
for
usual
are the
2951
we
aqueaus
problems
have
acid
to remove encountered
:
H-15o,
been used for the protection
and
difficult
manner
as t-butyf
: Amberlyst
for the preparation
reagent. in this
protected
are
catalyst
has already
in patents,
reaction
traces
have been
presence
This catalyst ethers7,
as is
practical
are,
removal
pheromones5.
in the
-S03H groups.
alcohols'.
its
for our organometalfic
as tetrahydropyranyl
from alkenes
group
introduction
syntheses
by reaction
of alcohols
traces
Thus
exactly
The c&rii-halohydrins, required
an acid
bulk
we
Cidex
of organulith~um
The
fact,
Paris
Et22
pheromone amounts
or Mg) by the
of course).
solvent,
most
in
destroyed
functionality.
in
(Li
insect
In
F-75252
45
are protected
FeC13
neither
large
ether’.
useful
solutions
of our large
ethers
of
tour
: Amberlyst
10%
ETHERS
impaired3.
encountered practical
field
tt-hydroxy
the
catalyst
are
of alkynes’,
Jussieu
alcohols
and
.OO
Colin
5.
des Organo-elements,
4 place
acid AcaO
systems
the
reaction
was
an by
dienic
a protected
purpose,
and
acetates
AS TER-BUTYL
f
SYNTHESIS
Gardette,
and W-acetylenic
isobutene
cleaved
) M.
de Chimie
- a,er-ttalohydrins
db.&xac.t
OF ALCOHOLS
OF PHEROMONE
A. Alex&is*
0040-4039/88 $3.00 Pergamon Press plc
not
of ethers
detected
catalysts4.
any
From
a
by distillation9, in
initiating
the
2952
Arsberlyst
R-OH
+
H-15
R-O-t-Bu
+
hexane
===c
A
LAO t
HCGC-FH-Pr 0
A
The
Cl
deprotection
X = Cl,
step
for
was
the
Br,
+
I
n = 3,4,6,8,10
studied
reaction T-2
methods
X-(CH2)n-0
+
n = 1, 2, 3
%
carbocupration known
HC:C-(Ct$)n-0
HCZC-CH2-:H-BU
.
The
removal
of
mainly
two
on
the
following
the
t-butoxy
olefinic
compounds
4,lO
group
products were
obtained
used
to
test
after the
the
various
.
Me
(CH214-0 +
-A The
first
one
functionality favorable system whe
one
although that the of
the
of
the
destruction
diethyl
the
Lewis since
ethylenic
we tried
compounds
O.leq.,
Although,
under
where
hand
similar
cyclisation
the
second
and
is quite
11 ,
we
noticed
t-butoxy
group
ether,
they
may these
;
of the of the
-A and -B.
acid
system
of FeC13,
structurally
position other
modification
and
satisfactory
bond
to
to
one
E
a
isobutene
of
an
tetrahydropyran
possess
representative
and
the
a
Z,Z
kind
oxygen
ring
is
conjugated
of
insect
a
diene
pheromones
prepared5.
complete
a complete
Ac20
a
the
isomerlsation
cleavage
sensitive
double
at On
the methods
partially
the
to
already
all
a
placed
prone
for
has
process.
have
Among
-A
lnstead as
the
tetrahydrofuran, be
increased
new
to
conditions,
FeC13
reactlon on the 0.3 the
eq.
system
allow,
as solvent,
solvent.
of
one
or dienic
conditions
of Ac20
12 system was the fastest 3 minute at room temperature),
Ac20/FeCl
than
monoethylenic
Et20,
down
the
(less
reaction
character
slow
that
The
;
role
methylene
rate
without
other
hand,
in
the
reaction
cases
takes
was
now,
we use of
occuring.
a mild only
Et20
polymerises
five
on eq. mask
are
not
destructlon
of
readily.
hours,
found
to
pentane
the
secondary
several
to
probably,
or
preventing
of
three
is,
chloride
We
deprotection
The
t-butoxy instead
amount ethers. of
less
2953
than one minute, acetates,
we were able,
now,
without isomerisation
to
obtain,
in
high
of any of the tested
yield
dienes
following
the
,
or enynes
14
desired
:
Et20 + 3-5eq. AcZO +
R-O
O.l-0.3eq.
FeC13
A
R -0Ac
+2OT
+
2-15 h Me
Me
===c (CH~)~-~AC
IA
II = 6, 8, 10
(CH21n-OAC
Ety(CH -0Ac 26)
Perk 0
0
Pr
OAc
OAc
To a aoh(utLon UL t-buk& Ac20
i5 m! J ,
i%en
4a*curated
aqueou4
The nvW
ieP04
and ihe o~puc pwufced
elilen
anfqdmit4
i 70 nanoli F-etij
Z-75 houn4 untc-lno
A2mpe/ia_tune
Pr
I/
4oh5un ~4
of
i 250 4.xkzntixy
anh~(lzOU5
.in
rngi.
The
dwik
mahncd
I25mLl
NayP04
~4
bg &4tdutitcon
v/i
150 m4.J ane
b~wn
cd
Ieff
4o&&i.un
M
4ti/red
~cutioL
Lq
TLC
c4
extiacted.
tiue
oven Mg_Y04, .then concentn&ed.
duwmatopuph~.
iheyce.Ldo/Y Me
5
ducce44lvdg
uddedandthp.nux.tu.e LA
f&tuned off, the aqueuu4 layen
pka4e4 ane dued
Et20
(CH~)~-OAC’
w&h
added at
*IL
4.i1.4n~ed &en
worn
~LPCI. A 3 ti.
fan (50
dl
The dunk ncsudue ~4
,cxu.~fiiLeu makvu-ui
~4
u~uuAly
W-95%. Since, that its
now, the t-butoxy
protecting
use in pheromone synthesis,
We especially
organometallic functionality.
recommand it reagent
is
in all
group can be easily and also the cases
elsewhere,
and mildly
where the formation
hampered by the presence
of
removed,
we believe
should not be anymore restricted. or the reactivity
a classically
protected
of an alcohol
J. Normant,
A. Alexakis,
A. Alexakis, There
are
and
M. Gardette,
several
reactivity
Grignard T.W.
in
the
(1981) Tetrahedron
:
litterature
protected
acetal
-41
of
(OTHP,
5887
(1985)
diminished
OEE,
yields
OMEM,
in
etc...)
the
preparation
organolithium
and
reagents.
Greene
in "Protective
Commercially
There
are
deal
with
the
of patents
synthesis
Imaizumi,
Y.
203
Aldrich,
M. Orena, on
Fujiwara
1981 40
2741
(1984)
etc...
S. Sandri
:
topic,
from
terbutyl
Sekiu
:
Wiley,
Tetrahedron
:
(1987)
Fluka,
this
of methyl
Synthesis",
J. Normant
Chimique
from
G. Cardillo, dozens
in Organic
A. Alexakis,
L'Actualiti
:
available
Bongini,
groups
N. Jabri,
b/ A. Alexakis
a/ M.
841
J. Normant
reports of
a/ M. Gardette,
A.
Synthesis
Synthesis the
ether,
Gakkaishi
618
(1979)
petroleum
industry.
an antiknock -27
:
356
additive.
(1984).
C.A.
Most
of
them
See
for
ex.:
101
170.350k
(1984) b/ W.
Weier,
220.342
W.
g
Webers,
Dettmer
D.
Ger.
:
Offen
DE
322,
3,
753
(1985).
C.A.
102
P
121.810
s
(1985)
c/ G. Trevale,
G.F.
Buzzi
Braz.
:
Pedido
PI
BR
8205,
855
(1983).
C.A.
-99
P
(1983) These
traces
procedure
of alcohol
is not
convenient
a/ R.L.
Burwell
b/ M.V.
Bhatt,
S.U.
A
account
of
full
Universite
Jr
a/ E. Knoevenagel
c/ B. Ganem, d/ R.S.
eq.
(ROAC)
is
the
Most
(Received
Small
D.S.
402
Jr
are
:
or a Pd"
has
in the in
90-95%
were
France
have
Chem.
our
this
moles)
is
Chem. 39
reported
new
134
3728
17 1749
in
M.
Gardette's
thesis,
most
on the
other
51
(1932)
(1974)
(1987)
reaction
the
conditions
the
sensitive
dienic
hand,
not
the
does
alcohol
cleavage
systems
react
(ROH),
in
to
are Et20
but
acetate
partially
;
again
in
CH2C12
the
most
destroyed.
obtained
assisted
However,
(1983)
tried
hydrolysis,
by cleavage
coupling
reaction.
immediately
after
of the The
crude yield
t-butoxy of the
ethers
cleavage
after reaction
range.
to be quenched
formation
249
Comm.
under
are
Si02.
(1954)
J. Prakt.
:
However,
systems
(I-5
on
(1914)
Synth.
after
chromatography
1983
J. Org.
chloroformate,
compounds
we
133
:
used
scale
Synthesis
Paris,
Watt
affords,
is in the
results
Ann.
by flash
-54 615
methods
Curie,
ethylenic
reaction
:
Ethyl
of these
itself
large
faster.
carbocupration
The
on Rev.
even
reaction
sensitive
removed
H. Maier-Htiser
of AcCl
destroyed.
be
Kulkarni the
:
V.R.
Gross,
If two
Chem.
:
P. et M.
b/ H. Meerwein,
may
of enol 26
acetates.
February
1988)
completion.
Prolonged
reaction
time
a