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