The use of lithium borohydride for deprotecting acetylated alcohols and phenols in the presence of N-acetylated guanidines

Tetrahedron Letters,Vo1.27,No.47 Printed in Great Britain

THE USE OF LITHIUM ALCOHOLS

Didier

aInstitut Laboratoire

ALCON-POS,

In our study

either

to succeed,

rue

68240

b

I Guy ANDERMAMN

Humann

UA 589 CNRS) 67000

Kaysersberg,

and NaBH4

GUANIDINES

on various

Strasbourg

France

0- and N-acetylated

investigated.

of molecules

reactions

type of reaction

of LiBH4

has been

+a

(U 206 INSERM, 11

ACETYLATED

OF N-ACETYLATED

LECLERC

de Pharmacologic

quanidines

alkylation

Gerard

de Pharmacochimie,

: The behaviour

FOR DEPROTECTING

IN THE PRESENCE

HUBERa,

bLaboratoires

Summary

BOROHYDRIDE

AND PHENOLS

oo40-4039,'86 $3.30 + .OO Perqamon Journals Ltd.

,pp 5731-5734,1986

with

adrenergic

on the phenol

properties,

or the aicohol

we carried

functions.

the 2-(imino-2)-imidazolidines


CH,OR'

I

R

I Ia:

R=R’=H

Ib:

R =

Ic:

R=Ac,

R’=

na

: R = R"=H

AC

n

b : R = Rfl=Ac

R'=H

EC

Scheme 5731

I

: R=Ac;

out this

of I and II had

i

N

For

R”= H

5732

to be protected. reported

To date,

satisfactory

protecting

yroup

has been

in the literature.

N-benzylation genation

at least

the guanidine

and trichlorethoxy

through

is possible I but deprotection

(Pd/C) provokes,

Protecting

links.

no ent irely

carbonyl

partially,

function

residues,

hydrogenolysis

with

often

catalytic

of the Ar-Cl

I,1 dimethylethoxy

applied

hydro-

in peptide

carbonyl chemistry,

did not work. The most N-acetylated 18h

or

satisfactory

form

CH3-COCl

presence

technique

(1,2). However, in pyridine)

of an alcohol

this

was to protect rather

did not give

function

harsh

the quanidine method

selective

(Ia) or of a phenol

We tried

to obtain

the diacylated

derivatives,

different

desacetylatinq

reagents,

(Ac20, 80°C,

N-acetylation

one

Ib and IIb with

in its

in the

(iIa).

Ic and IIc, by treating

as described

in the

literature.

TABLE

I

Initial

K2C03/MeOH

product

Ib

NaHC03/aq.

MeOH

IIb

t-BuNH2

=q- NaOH

KCN/EtOH

O.lN/THF

(3)

no reaction

(5)

Ia

Ia

(1)

IIb

IIa

(1)

Ib

no reaction

Ib

Ic

IIb

IIC

LiCl/diglyme

I shows,

of potassium

no reaction

Ib

95%

As Table presence

product

Ib was completely

carbonate.

This was also

the case with

mixture.

desacetylated

product

Ia, whereas

IIb did not react.

The reactivity

of Ib could

be explained

the ester facilitated vation

function

by t-BuNH2,

by the assistance

has already

been

Ib with

followed

t-butylamine

among

gave

by the partial

acetylated

function.

in the

a sodium

also

by the N-desacetylation

of the beta-alcohol

described

(4)

desacetylated

hydroxide/THF

Treating

Reference

Id

Ib IIb

NaBH4,

End product

the completely

hydrolysis

of

reaction,

A similar

beta-aminoalcohols

obser(9).

5733

NaBH, Li Cl Diglyme CH,OH

CH/“Ac

Ib

AC

AC

,.I

NaBH, Li Cl

AcO

w

HO

Diglyme

I

‘Cl

AC

AC

Itb Scheme

Already

well

(6) has recently in the presence borohydrides cation

NaBH4

and LiBH4

reducing

deprotection

with

studying

Ib with NaBH4,

than LiBH4,

gave

properties

and with

properties

worth

phenol of

nature

than NaBH4

(10) gave

is supposed

a completely

of the

in

the reactivity

LiBH4

which

borohydride

of acetylated

the solvent

reducing

seemed

Ic. Surprisingly,

properties

sodium

(7). The reducing

on Ib and IIb. Treating

hand,

or LiBH4,

satisfactory

of

the N-dito have

desacetylated

gave

explanation

treating

the N,O-triacetylated

only the N-diacetylated has yet been

found

derivative,

derivative

IIb,

11~. MO

for this unexpected

behaviour

and LiBH4.

We are at present clonidine-type Our results selective

to vary

properties,

Ia.

with NaBH4

other

alcohol

has greater

It therefore

On the other

of NaBH4

for selective

shown

LiBH4

compound,

derivative,

used

have been

solvents.

acetylated lower

been

for its reducing

of acetylated

(8). Thus,

etheral

known

II

applying

this

selective

desacetylation

method

derivatives. show,

0-desacetylation

for the first

time,

in the presence

that LiBH4

can be used

of N-diacetylated

for

guanidine.

Acknowledgements We thank ALCON-POS Dr. J.D.

Ehrhardt

Laboratories

for interpretation

for financial of mass

spectrum.

support.

We thank

to

5734

References -- and notes 1.

Rouot,

G. Leclerc,

Eur.

2. B. Rouot,

G. Leclerc,

Bull.

B.

Pattner,

3. J.J.

R.D. Glass,

J. Med.

(1978) -13 : 6, 521. (1979), II : 520. J. Amer. Chem. SoC. (1972))

Chem.

Sot. Chim.

Fr.

H. Rapopart,

-94

:

8613. 4.

M. Tominaga,

K. Mori,

T. Takigama,

5. G. Biichi, S.M. Weinreb, 6. S.W. Chaikin,

8. H.C.

W.G.

J.K.

7. J, Quick,

IO.

Brown,

Crelling,

Brown,

J. Amer.

(1978), -43 : J. Org. Chem.

Y.M. Choi, J.D.

was

with NaBH4

(1973), 790.

(1971), -93 : 746. Sot. (1949), -71 : 122.

Chem.

Chem.

G. Leclerc,

Synthesis

Sot.

Ehrhardt,

Bull.

1,

155.

(1982), 47 : 4702. Sot. Chim. Fr. (1985),

1230. (20 mmoles)

50 ml of diglyme

spectrometric treated

with

treated

for

18 h at room

there

chromatography,

data of compound NaBH4

(79%) of IIC.

'H NMR

consistent

with

: IR 3440,

4.8(s,

1680.

308/310 (Received

(IOO), 228/230/232 in France

usual

and

(84%) of Ic. As an example, here.

(20 mmoles)

IIb

MS,

IR(CHC13,

the

(20 mmoles)

was

in 50 ml of diglyme

and chromatography,

CDC13),

(20 nunoles) in work-up

cm-l)

we obtained spectra

5.2 g

were

structure.

'H NMR

IH); 6.7 - 7.5(m,

and LiCl

work-up

(60 MHz,

assigned

5.8 g

and LiCl

After

Ic are presented

(20 mmoles)

at 5O'C. After

(20 mmoles)

temperature.

was obtained

for one night

IC

M. Matsui, Chem.

J. Org.

S. Narosimhori,

9. M. Bouzoubaa, -6: 15

J. Amer.

2.1(s,

3H); 2.7(s,

3H). Mass

spectrum

(35).

15 September

1986)

3H); 3.8 - 4.2(m,

m/z

(%) : 343/345/347

5H); (60),