Hydrazinedithiocarbonate (HDTC) as a new reagent for the improved removal of chloroacetyl and bromoacetyl protective groups.

Tetrahedron Letters,Vo1.24,No.35,pp Printed in Great Britain HYDRAZINEDITHIOCARBONATE REMOVAL

OF

(HDTC)

CHLOROACETYL

Organon

Abstract acetyl

Scientific

Development

conditions,

is described.

which

The availability improvement

of convenient

of existing

chemistry.

It is essential

necessary

for halogenation

Temporary

protective

which

groups 2)

-trichloroethyloxycarbonyl Unfortunately, ethers

decreases

several

for instance,

during

during

many

now this

ester

to side

protective reactions

In this groups

group

and to present

yield

temperature

depicted

in Scheme

of thiourea

(Ia)

reaction

shown

to fulfil

usually

we wish

(see 1A.

group Table,

2 reaction

in which amide

entry

1).

,

demands

the use of these

group reactions

steps

. The

of Hg(CN12

protective

relatively

5)

group,

1)

I 2,212

groups.

and form

labile

a complex

to base

levulinoyl

3)

group

and may

be

2b) . because

chemistry.

strenuous

mild

groups.

protective

is highly 1)

under

are ally1

1)

Further-

esters.

and chloroacetyl

in carbohydrate

an improved

method

group.

treatment

it can cope Unfortunately

conditions

which

intermediate

LTa first

lITa.

of intermediate 3775

slightly

mechanism

ester

for the removal

The most

under

The two-step

of chloroacetyl to give

the conditions

give

with up to rise

1).

is thiourea entry

mild

as the

reactions.

and acetyl

in two distinctive

as a new protective

the NH2-group

IXa.

under

to present

The chlorine N

with

convenient

be removed

coupling

these

in the presence

employed

under

in carbohydrate

to withstand

ethers

4)

levulinoyl

The trichloroacetyl

be a very

bromoacetyl

in an S

the cyclic

been

in coupling

as well

that they can be removed

as benzyl

performed

and bromo-

deprotection

importance

stable

such

be removed

.

in Table,

the chloroacetyl

elevated

molecular

must

communication

of removing

forming

could

conditions

(see

6)

reactions

reactions

groups

,

GROUPS.

of chloroacetyl

groups

and of subsequent

are associated

must

protective

to be sufficiently

3)

IMPROVED

derivatives.

are of fundamental

trichloroacetyl

THE

The Netherlands.

is the selective

and persistent

of the carbohydrate

coupling

of the reaction

,

reagent

centre

BH Oss,

for the removal

groups

have

usually

coupling

The chloroacetyl

of this

protective

disadvantages

the reactivity

unstable

5340

for temporary persistent

Hg

Box 20,

groups

that do not affect

with

P.O.

procedures

conditions

2+

Group,

of the anomeric

it is a prerequisite

Ally1

Beetz

(HDTC)

FOR

PROTECTIVE

and T.

on carbohydrate

for these

REAGENT

Boeckel

temporary

removal

NEW

van

The advantage

was demonstrated

A

BROMOACETYL

The use of hydrazinedithiocarbonate

:

groups

more

AS

AND

C.A.A.

0040-4039/83 $3.00 + .OO 01983 Pergamon Press Ltd.

3775-3778,1983

widely basic

of chloroacetyl

accepted conditions

underlying is substituted

this

displaces

at

procedure

by the sulphur

The next step consists

ma

method

the alcohol

of an intraROH

(Q)

is

3776

A:

ii

+

A

H,N

CICH,COR ’

-

[N<;B&“J-NpO

+ROH

NH,

Ia

Jla

B: NH,NHQ

ii

ma

8

+

XCH,COR

lYaH

Y

+ RoH

Ib

lib

mb

ii)

to facilitate

improve

the

by enhancing The

the

with

nucleophilicity

that

the

highly

from

the

effective

possibilities

group

in that

compounds

la,

z,

was

the

for

(see

it has and%

ii)

by introduction

leaving

intramolecular

group

of

(Scheme

entry

group

at this

2

can

of the

2)

group,

displacement

bromoacetyl

2)

to give2

could

moment

little

is

group.

already

in 90% yield.

be circumvented

group,

we also

known

chloroacetyl

had the

protective

about

For

be This

by taking

sulphur a smooth

and nitrogen cleavage

intention

group

Hydrazinedithiocarbonate

iii).

nucleophilic revealed

the

by a better

result

advantage

the

properties

chemistry.

of the

and

atom

facilitate

Table,

of a bromoacetyl

under

chlorine

atom.

bromoacetyl

cleavage

iii)

realized

However,

group.

the

atom,

of a chloroacetyl

introduction

mentioned

requirements

i)

in carbohydrate

reagent

replace

nitrogen

temperature

removal

protective

bromoacetyl

Apart

that

at room

sluggish

of a bromoacetyl of the

under

i)

sulphur

of the

established

thiourea

we can

of the

mentioned

it was

cleaved shows

nucleophilicity

possibility

instance,

deblocking

P

1

SCHEME

In order

Ipb

atoms.

of developing

by applying

(HDTC

, Ib)

Model

studies

of the chloroacetyl

group

8)

a

the meets with

these

HDTC

on

at room

temperature. In a typical

experiment

and added

to derivative

and acetic

acid

room

temperature

chromatography

(0.6

HDTC 12 (0.25

ml).

without afforded2

TLC the

was

prepared

mmole), analysis

formation

in 96% yield

in situ

which

was

revealed of side (see

8)

(2

of standard

dissolved

a complete products.

Table,

ml

entry

in a mixture deblocking

Work-up 3).

solution, of

within

and purification

0.75

lutidine lo-20

mmole) (1.8

min.

ml) at

by column

3777

SCHEME

2

L

HDTC Bn OBn ,@X=CI b:X =Br

e

HDTC

XCHj 2

Bn OBn

za:x=ci b:X=Br

HDTC I

bBn ?a :X=CI b:X=Br

B” =Be”zy’8 HDTC = NH,NHC+

entry

compound

reagent

IIa

thiourea

P

ao-100°C

lb

thiourea

2

r.t.

120

90

la

HDTC

2

r.t.

10

96

lb

HDTC

2

r.t.

2

98

3a

HDTC

4

r.t.

20

88

ii ry

HDTC

4

r.t.

2

95

5a ry

HDTC

6

r.t.

15

96

HDTC

6

r.t.

2

99

z?

product

temp.

time

(min.)

30-120

yield 40-805)

(%I

3778

It was found minutes

that under

at room

Finally,

temperature

selectively

deblocked

HDTC

under

(see

Table,

entries

be cleaved

which

c)

protective

J.

without

a bromoacetyl

entry

affecting

other

described,

group

was cleaved

within

two

4). and bromoacetyl

ester

gave

functions.

protective

Thus,

groups

treatment

could

of z,

compounds4_and&respectively

be

b and 52,

in high

b

yield

5-8).

more

reagent,

References

Table,

the preliminary

much

conditions

that chloroacetyl

the conditions

In conclusion,

1. a)

(see

it was established

with

other

the same

easier

cleaves

studies

here show that a)

than the chloroacetyl

chloroacetyl

groups

presented

group,

and bromoacetyl

are not affected

b)

HDTC

protective

by HDTC

the bromoacetyl

is an easily

groups

under

Letter:,

1191

group

can

accessible

mild

9)

conditions

and notes Cunningham,

b)

E.J.

Corey

c)

J. J.

Oltvoort,

R.

Gigg

and W.J.

and C.D.

Suggs,

C.A.A.

J.

Tetrahedron

Warren, Org.

Chem..,

, J.H.

van Boeckel

38,

3224

de Koning

(1964).

(1973),

and J.H.

van Boom,

Synthesis,

305

(1981). 2.

a)

T.B.

b)

C.A.A.

Windholz van

(1980) 3. 4.

a)

V.

Schwar

b)

H.

Paulsen

z,

J.H.

van

b)

H. J.

Koeners,

c)

C.A.A. A.F.

b)

M.

c)

C.P.J. 271

Boom

Johnston,

Czech.

Biinsch,

and J.H.

and J.H. Cook

Naruto,

Letters,

2555

van Boom,

K.

Glaudemans

N.

van

Hermans, Tetrahedron

Maichuk,

J.

Naruse

and M.J.

27,

114,

(1967).

Tetrahedron

Org.

P.

2567

3126

Tetrahedron

and J .H.

J.P.G.

Ohno,

Commun., Berichte

Burgers,

van Boom,

and D.T.

Chem. Chem.

Verhoeven

van Boeckel,

Letters,

1571

Letters,

Boom,

1951

Chem.,

35,

and H.

Takeuchi,

Bertolini,

Methods

4875

Tetrahedron

Westerduin,

Letters,

(1962).

(1981). (1976)

Letters,

J.J.

. 381

Oltvoort,

(1980).

G.A.

van der

(1982).

1940

(1970).

Tetrahedron

Letters,

in Carbohydrate

251

(1979).

Chemistry,

vol

VI I I,

(1980).

E.

Walker-Nasir

7.

H.

Paulsen,

8.

A stock

and R.W.

Angew.

solution

in dioxane

(6 ml)

Jeanloz,

Chemie

of HDTC

155 (1982).

was prepared

by dropwise

solution

(30 ml,

2: 1, v/v)

15 mmole).

also T.

Curtius

3,

HDTC

S.

See

(0°C)

Res.,

also

cleaves

of hydrazine

in the presence

in UK 20 June

1983)

343

(1979).

of CS2 hydrate

(0.7

ml,

(0.73

ml,

of diisopropylethylamine

and Ft. Heidenreich, N-chloroacetyl

68,

adding

221).

presumably

(Received

Carbohydrate

Ed.,

to a cooled

Int.

in ethanol/water Bd.

Tetrahedron

Westerduin

and P.M.J. J.

6.

9.

P.

Collect.

and H.

a)

a)

and D.B.R. Boeckel,

.

Mare1 5,

,

treatment.

groups.

Ber.,

z,

58 (1894)

15 mmole) 15 mmole) (2.61 (cf.

ml,

Beilstein,