A chiral reagent inducing asymmetry in electrophilic amination reactions

Tetrahedron L e t t e r s , V o l . 2 3 , N o . 5 1 , p p Printed in Great Britain

A CHIRAL REAGENT

5403-5406,1982

INDUCING A S Y M M E T R Y

IN ELECTROPHILIC

Gernot Boche* and Wolfgang Fachbereich

Chemie der Universit~t

0040-4039/82/515403-04503.00/0 © 1 9 8 2 Pergamon Press Ltd.

Marburg,

AMINATION

REACTIONS

Schrott

Hans-Meerwein-Stra6e,

D-3550 Marburg

Abstract: The chiral amination reagent (-)-! was prepared from (-)-ephedrine,configurationally determined by X-ray structure analysis and reacted with carbon nucleophiles to yield the optically active amines 4a-d with up to 44% ee. Among the many reactions which have been developed

for the preparation

compounds within the last decade I , only few deal with chiral induce asymmetry, munication structure

as shown by recent publications 2"3.

of Kjaer and Malver 3 that prompts determination

of the absolute

It is especially

us to disclose

configuration,

of chiral

leaving groups to the com-

the synthesis,

and application

of

X-ray (2R,4S,

5R)-2-O-(N,N-dimethylhydroxylamino)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidin-2-one,

(-)-!,

Preparation

of

for the formation of chiral amines.

(-)-~. When

(-)-ephedrine

was reacted with phosphorus

oxychloride

of N , N - d i m e t h y l h y d r o x y l a m i n e via (_)_~4.

H OH

NEt

0

with the hydrochloride

(-)-! was formed in 68% yield

H O - N \ c H 3 "HCI

H C.L-dP'Ct

CH2CI 2

CH 3

dichloride/triethylamine

and subsequently

((CH3)2N-OH'HCl),

POCi3j

NH

in methylene

NEi3

I CH 3

O

~0 jCH 3

'

N'P "~O-N \CH3

CH2Cl 2

CH 3

c-/-2_ Similarly, one-pot

f~om

(+)-ephedrine,(+)-!

is easily accessible

by means of this

synthesis 5.

Confi@uration

Since the absolute

configuration

of

(-)-ephedrine

known 6, it was easy to assign the absolute

of

(-)-!.

configuration

of

(-)-! from its X-ray

structure 7. As shown by the ORTEP drawing amino group

(Fig.

I), the N , N - d i m e t h y l h y d r o x y l -

is on the same side of the five-membered

C 4 and C 5. Thus,

the t r a n s f o r m a t i o n

tion at the phosphorus

is

ring as the substituents

at

~--+~ occured under retention of configura-

atom.

5403

5404

/ O (~ .____~_~ 2~/ /(51 H

/

N(CH3)2 CH 3

(z,l\ H

CH 3

(-)-1 =

.'

Fi~.

I. ORTEP d r a w i n g

Formation

of chiral

action w i t h i n various

the

amination

last

few years

reacted

I. A s y m m e t r i c to give

results

(-)-~.

allows

in all kinds amines with

4a-d d e t e r m i n e d

not yet o p t i m i z e d

of

The d e v e l o p m e n t

of chiral

3a-d were

of the products

Tab.

amines.

reagents

in the p r e p a r a t i o n compounds

and n u m b e r i n g

are

induction

by

of the e l e c t r o p h i l i c

the

introduction

amination

of amino

groups

of n u c l e o p h i l e s 8-11 . We were

by this method.

Therefore,

(-)-! and the amount by o p t i c a l

listed

[i

rotation

in Tab.

excess

reagents.

The

(-)-~ in e l e c t r o p h i l i c

amination

reactions

R1

C6Hs-C-M ~2

I

-

C 6 H s - C - N (CH3) 2 L R2

THF

amine

[°C] H

% yield

4 opt.

yield

-15

~

63

BO b)

C 6 H s -C -MgC 1 J CH3

-75

4a

46

24 b'

H

-15

~

40

44 b)

-75

4a

35

19 b )

I

CGHs-C-MgBr I

CH3

with

~.

(-) -I=

~'

(% ee) first

I.

R1

~

with

interested

the o r g a n o m e t a l l i c

of e n a n t i o m e r

or shift

re-

(% ee) a)

5405

H Z

3a'__,d)

(C6Hs-C-)3B

----

-10

4a

26.5 e)

11 b)

-15

~

50

23 c)

-I 5

4c

56

21 c)

-15

4d

62

I

CH3 H ~

C6Hs-COLi ~ I

C02Et

CH3

3c

C6 Hs-C°Li e C02Et H I

3d

C6 Hs-C~Li ~

8c,f)

I

CN a) optical purities

given as % ee

tion after gc purification the Grignard

reagent;

f)presumably,

(error ±5%) were determined

and C)with Eu(tfc)~

e)the yield

by b ) o p t i c a l

in CDCI3 ; d)prepared

is related to three alkyl groups

the ee value does not correspond

duction because of facile racemization

rota-

in situ from in ~ ' ' ;

to the amount of asymmetric

of ~d during normal acid

in-

(pH 4.5)/base

(pH 8) workup. Further

substrates

and optically

chiral amino alcohols Acknowled@ement:

Industrie

Englewood

Cliffs,

rentiating

Reactions", I_~I, 375

Res.

stry I~0, 175

for financial

f) P.A. Bartlett,

New Jersey,

from and

support.

Academic

"Asymmetric

Tetrahedron

W.S. Murphy,

c) C.P.

Press, New York,

Reactions",

Prentice

"Stereodiffe-

1977; c) A.I. Meyer_~s, Acc.

J.C. Fiaud, Topics

R.P. Sequin,

in Stereochemi-

Tetrahedron 35, 2797

(1979)

3_66, 2 (1980). J. Chem.

Soc., Chem.

634; b) J.M. Wilson, Duhamel,

Organic

1972; b) Y. Izumi, A. Tai,

(1978); d) H.B. Kagan,

Perkin I, 1976, (1982);

H.S. Mosher,

(197~)j e) J.W. ApSimon,

2. a) P.G. Duggan, 881

reagents

and Notes

Chem.

Soc.

amination

and diols are under investigation.

I. e.g. a) J.P. Morrison, Hall,

electrophilic

We are very grateful to the Deutsche F o r s c h u n g s g e m e i n s c h a f t

the Fonds der Chemischen References

active,

J.-Y. Valnot,

Commun.

D.J. Cram,

1974,

263; J. Chem.

J. Am. Chem.

J. Jamal Eddine,

Soc.

104,

Tetrahedron

Lett.

1982, 2863. 3. A. Kjaer, agent

O. Malver,

Tetrahedron

Lett.

1982,

2687,

reacted the amination

(+)-O-(~-bromocamphor-~-sulfonyl)-hydroxylamine,

p-tolyl

sulphide;

a few percent".

the aminated

Isolation

product

had an

of the optically

re-

e.g., with methyl

(R)-enantiomer

pure compounds

excess of "only

therefore was

5406

achieved by crystallization. 4. D.B. Cooper, C.R. Hall, J.M. Harrison, 1977,

T.D.

Inch, J. Chem.

Soc.

Perkin I,

1969.

5. The following general p r o c e d u r e applies milar a m i n a t i o n reagents)

from

for the p r e p a r a t i o n of

(-)-ephedrine

diols) : To 0.10 mol amino a l c o h o l / d i o l and 50.6 g 700 ml CH2C12

was added

15.3 g (0.10 mol)

(-)-!

(and s i -

(and similar amino a l c o h o l s / (0.50 mol)

triethylamine

in

POCI 3 at -5°C. Then the reaction

m i x t u r e was stirred at I0°C for 14 h. A f t e r the addition of 9.75 g (0.10 mol) (CH3)2N-OH'HCI s t i r r i n g was c o n t i n u e d at 20°C for another 24 h, the ether insoluble a m m o n i u m salt separated by filtration,

and the solvent evaporated.

C r y s t a l l i z a t i o n or column c h r o m a t o g r a p h y p r o v i d e d the a n a l y t i c a l l y pure product. [~50

(-)-!:

18.5 g

= -276.1

(C

6. S t r u c t u r e of

(68%); m.p.:

= 2.57,

140°C

(diisopropyl ether); [ ~

=-82.7;

CHC13) .

(-)-ephedrinehydro~loride:

R. Bergin, Acta Cryst.

B27, 381

(1971). 7. We are v e r y g r a t e f u l to Dr. W. Massa and G. Baum, v e r s i t ~ t Marburg,

8. With O - a l k y l - and O - a r y l h y d r o x y l a m i n e s : Z. Nir, T e t r a h e d r o n 28, M.J. Miller,

F a c h b e r e i c h Chemic der Uni-

for the X-ray structure determination.

J. Org.

3833

a) T__t. Sheradsky,

(1971) ; b) A.S.

G. Salemnik,

Radhakrishna,

Chem. 44,

4836

(1979).

9. With O - s u l f o n y l h y d r o x y l a m i n e s :

ref.

3 and a) M. Takeishi,

Kyokai Shi 28,

1171

J. Minamikawa,

M. Ikeda,

Acta 13, Chem.

(1970); Chem. Abstr. 74, Synthesis

1977,

T. Abraham,

(1978); Angew.

Chem.

Yuki Gosei Kagaku

(1971) ; b) Y. Tamura,

M. Bernheim,

Int. Ed. Engl.

(1978); e)

f) E.C. Taylor,

10. With O - p h o s p h i n y l - and O - p h o s p h o r y l - h y d r o x y l a m i n e s :

a) M. Bernheim,

Angew.

Sun,

Synthesis

Chem. 92,

b) G. Boche,

1980, 801.

1043

(1980); Angew.

F. Bosold, M. NieBner,

G. Boche, M. Bernheim, M. Bernheim,

151

Angew.

Soc., Chem.

Commun.

J. Organomet.

J. Am. Chem.

Chem.,

Soc.

d) D i s s e r t a t i o n

f) M_~.J.P. Harger,

H. Baldinger,

147

K.A.R.

Russ. Chem.

(1980) ; Angew.

Univer-

J. Chem.

E_t.M. Karpitschka,

Sastry,

Rev. 45, Chem.

G.W. McCollum,

1982, 62; d) B.H. Mikhailov,

Chem.

103, 2483

Jr.., T e t r a h e d r o n Lett.

in print;

G. Boche, (1980) ;

3255; c)

1981; e) D i p l o m a r b e i t W. Schrott,

a) E. Schmitz,

Chem. 92,

(1980); c) G.W. Kabalka,

Etinger,

Angew.

1982,

1010

1982, 592.

11. Other a m i n a t i o n reagents:

Chem.

Int. Ed. Engl. 19,

T e t r a h e d r o n Lett.

3284; g) W. Kl~tzer,

Synthesis

F. Effenberger,

Chem.

1980, and u n p u b l i s h e d results;

Soc. Perkin I, 1981, J. Knoflach,

M. NieBner,

U n i v e r s i t ~ t M~nchen,

sit~t Marburg,

1019

K. Wagner, Angew.

I_/7, 687

(1982);

J.-H.

D. Curran, T e t r a h e d r o n 38,

Loudon,

I; c) R.G. Wallace, A l d r i c h i m i c a

3 (1980); d) G. Boche, N. Mayer,

9_O0, 733

75683m

G.M.

220,

f) A. Hassner,

699.

(Received in Germany 29 September

C.A. Lane,

1982)

I_~9,

J.

E_z.A. Shagova, M. Yu

I (1981) ; e) B.M. Trost, W.H.

(1981);

1982,

16 (1976); b)

Int. Ed. Engl.

P. Munger,

Pearson,

B.A. B e l i n k a