Short-step synthesis of amino acids and N-hydroxyamino acids from amines

Tetrahedron Letters,Vol.28,No.51,pp Printed in Great Britain

SHORT-STEP

SYNTHESIS

OF AMINO

Shun-Ichi Department Osaka

Summary:

University,

to give

inexpensive

method

Recently

for synthesis

that

hydrogen

peroxide

dioxide2

catalysts

reaction

of nitrones

strategy

for the introduction

We report acids

here

hydrogenation

Scheme

1)

H202,

nucleophiles

provides

acids

cyanation,

with

step.

The

a potential

at the a-position

amines,

of amines.

(2) and amino hydrolysis,

and

1.

CN

Na2W0,, c

2)

CN

H20,

KCN,

R’ R2&N-R3

HCI

, AH

C02H

H+

R’ R2&N-R3

t

C02H H2

R’R2&N-R3

1 AH

*

R’ R’&N-R3 H

cat

AH

I

?.

N-Hydroxyamino

acids

bearing

accessible,

bearing

3

secondary

although N-hydroxyamino 3 prepared. Only one report

acids

and

or selenium

in a single

R3 H-

amino

amines

tungstatel

nitrones

in Scheme

(1).

catalytic

efficient,

of secondary

of N-hydroxyamino

of secondary

peroxide

from amines.

sodium

of substituents

as depicted

undergo

is a simple,

of either

synthesis

hydrogen

a-cyanohydroxylamines

acids

the oxidation

with

with

560, Japan

1

R’ R’CH-N

readily

This

of amino

thus obtained

short-step

gave

Science,

Osaka

(2), which

the corresponding

(3) by the oxidation

catalytic

(3).

in the presence gave

amines

cyanide

FROM AMINES

Shiota

Toyonaka,

acids

acids

ACIDS

of Engineering

of secondary

hydrogen

amino

we reported

and Tatsuki

Machikaneyama,

with

0040-4039/87 $3.00 + .OO Perqamon Journals Ltd.

N-HYDROXYAMINO

Faculty

of 1 gave N-hydroxyamino

hydrogenation

AND

Murahashi-

oxidation

by treatment

Hydrolysis

ACIDS

of Chemistry,

Catalytic

followed

6469-6472,1987

amino

groups

are hardly

acids with

primary

deals

the synthesis

with

amino

groups

can be

of N-hydroxy-

amino groups by Cope rearrangement of 4 acid N-oxides. N-Hydroxyamino acids are biologically

N-cyanoethylamino

secondary

important

ciass

are produced by metabolism of amino acids 6 and act as antibiotics and growth factors. For synthesis of amino acids 7 bearing secondary amino groups there are few general methods. Cyclization reactions

are generaily

steps

of compounds

and expensive

used,

starting

which

however, materials 6469

they are tedious 8 are required.

because

5

long reaction

6470 u-Cyanohydroxylamines amines

with

tungstate cyanide

are readily

30% hydrogen

in water

peroxide

or methanol

and 4 N hydrochloric

the preparation

and subsequent acid

in 72% isolated

gives

reaction

It is noteworthy corresponding cyanide.

that

nitrones

substituted

(4) with

Hydrolysis N-hydroxyamino

the treatment

acids

in excellent

palladium

on charcoal

Preparation

of

gave

of proline,

was

can be converted

into

of secondary

exclusively.

the reaction

conditions.

can be converted

bases

by elimination

into the

of hydrogen

of Z-cyano-l-hydroxy-

solution

l-pyrroline

gave

under

yields

acidic

as shown acids

the corresponding

a -Cyanohydroxylamines CI-Cyanohydroxylamine

N-oxide.

conditions

in Table

2.

over palladium

amino

from b

Further black

Proline

acids.

Secondary

gave

or

(7_) and

Aminesa Isolated

Yield/%

C3H7$H-tj-C,,H9

(C4Hg12NH

CN OH

0fl

2

72

I! OH

80

3

4

70

s OH

5=

92 CN

a)

The

reaction

b)

The

products

c)

Nitrone

was carried gave

was prepared

out

similar

satisfactory in CH30H

to the

The

of l-cyano-Z-hydroxy-

of a solution

of N-hydroxyamino

Amine

1=

NaOH

of

1.

1-cyano-3,4-dihydro-

under

with

of n-cyanohydroxylamines

hydrogenation

Entry

formed

treatment

an aqueous

catalytic

1.

gave

results

in Table

nitrones

u-cyanohydroxylamines

upon

For example,

pyrrolidine

once

potassium

the oxidation

from dehydration

is derived

1,2,3,4-tetrahydroisoquinoline

Table

(z), because

stable

of secondary

% of sodium

with

are summarized

of i,2,3,4-tetrahydroisoquinoline (6), which

treatment

2-dethylpiperidine

yield.

thermodynamicaliy

isoquinoline

of 4 mol

(4_), -which is a precursor

2-cyano-l-hydroxy-2-methylpiperidine amines

by the oxidation

The representative

in water.

of a-cyanohydroxylamines

2-Cyano-1-hydroxypyrrolidine obtained

prepared

in the presence

procedure

IR,

NMR,

mass spectral

by

using

3 equiv

described data,

of H202.

in the and

text.

elemental

analyses.

6i171

pipecolinic acid

acid

(9), which

(8_)were shows

obtained

peculiar

in excellent

behavior

yields. a-Methylpipecolinic 9 was also prepared

in proteins,

readily. As a typical described.

example,

To a solution

(0.358 g, 5.03 mmol)

in H20

(1.28 g, 11.3 mmol)

dropwise

O-5 'C, to the reaction mmol)

stirring

by adding CH2C12

followed

acetate

at O-10

a few dropps

under

was

added

argon.

NaOH

chromatography

and Pd-black

(i$)l'

temperature

under

solution.

on silica

solution

reduced

Careful

Removal

(1 atm).

After to pH 8-9

extraction

with

(eluent=hexane/ethyl A solution

stirred

pressure

of 4

at 50 'C for 8 h and ion exchange acid buffer)

(2 mL) was

stirred

of the solvent

at

gave proline

(0.107 g, 93%).

(1)12

The present practical Further,

Table

because various

2.

method

for synthesis

of amino

acid

is convenient

and

of high yields and the use of inexpensive reagents. 14 [l- Cl-labelled amino acids, which are important class

Preparation

of N-Hydroxyamino

a-Cyanohydroxylamine

Entry

Acids

N-Hydroxyb amino Acid

and

Amino

YieldCl%

1

Acidsa

Amino

Acidb

Yield’/%

CL

93

!

C02H

93

7 _

2

C02H

86d

CM3

3

CM3

d

CO2H

8ge

e

C02H

go

g7

OH rt a)

gave

of ;fJ (0.131 g, 1.00 mmol)

(2 mL) and methanol

hydrogen

at

(0.490 g, 7.52

ice cooling.

M pyridine-acetic A mixture

solution

was adjusted

gel

(4 mL) was

under

(0.977 g, 93%).

(0.021 g) in water

H202

4 lo (0.409 g, 72%).

of the solvent

is

3 h of stirring

cyanide

(1.8 mL) with

(Dowex 50W x 2, eluent=0.2

N-hydroxyproiine

After

potassium

HCl solution

in cone HCl

Removal

chromatography

a 30% aqueous

argon.

'C for 4.5 h, the solution

of 2 N aqueous

by column

from pyrrolidine

(0.067 g, 0.20 m-nol) and pyrrolidine

at 0 'C under

1:l) gave a-cyanohydroxylamine

(0.896 g, 7.99 mmol)

of proline

(3 mL) was added

mixture

and then a 4 N aqueous

additional

room

the synthesis of Na2W04*2H20

The

reaction

b)

Satisfactory

c)

Isolated

e)

Palladium

was carried IR,

yields.

NMR, d)

on charcoal

out

similar

mass spectral

The

hydrolysis

(5%)

was used

to the data,

procedure and

was carried

described

elemental out

at

as a hydrogenation

analyses 100 OC. catalyst.

in the were

text. obtained.

of

6472

compounds

with

respects

can be readily

and biosynthesis, labelled

to the tracer

prepared

Mitsui,

3)

T. Shiota,

and T. Shiota,

and G. B. Brown,

H. T. Nagasawa, Is,

483

Chem.,

and 0. W. Griffith,

Bull.

Yuki

a) G. C. Barrett,

Gosei

Marcel

Yoneda,

Pharm.

Polym.

J., g1

C. G. Overberger 1413

and Hall,

2583

Chem.

Chem.

(1987).

(1976); b) E.

and A. A. Mikhail,

J. Med.

J. Mol.

z,

2748

(1979);

86,

63

697

(1986).

(1982).

of the Amino

Acids",

Ed. by

1985, p 246; b) A. B. Mauger,

Acids,

New York,

Chem.,

(1974); c) H. C. J.

Rev., 40,

New York,

of Amino

Dekker,

Sot. Jpn., 9,

Chem.

2383

2092

Peptides,

1977, vol

Catal.,

and Proteins",

Ed.

4, p 179; c) I<.

41,

135

Synthesis,

Korenczlci, Synthesis, Eur.

Sot.,

(1967).

J. Biol.

Kyokaishi,

and S. Asada,

S. Nishii,

a) H. J. Monteiro, Chem.

J. Chem.

28,

3,

265

and Biochemistry

and Biochemistry

by B. Weinstein,

Bull.

Kagaku

"Chemistry

G. C. Barret-t, Chapman

Izawa,

32,

Sot. Jpn., 47,

and J. D. M. Herscheid,

7)

10) 4:

with

(1972).

Chem.

"Chemistry

Lett.,

P. S. Fraser,

b) A. Ahmad, Ottenheijm

Murahashi,

J. Org. Chem.,

J. Org.

a) A. J. L. Cooper

M. Akiyama,

9)

and S.-I.

J. G. Kohlhoff,

6)

8)

reactions

and Notes

Tetrahedron

a) T. Polofiski and A. Chimiak,

Chem., 5)

the present

874.

Murahashi

S.-I.

Buehler 4)

S. Zenki,

1984,

Commun., 2)

by using

of metabolism

K14CN.13

References

H.

for the study

experiments

1974, 137; b) T, Fujii -1341 (1975); c) H. Yasuo,

(1987).

and M. Miyoshi, M. Suzuki,

and N.

Bull.,

27 1931 (1.979); d) L. Kisfaludy and F. ---I 1982 163; e) C. G. Overberger and M. D. Shalati, ---I 1055 (1983).

and ii. S. Jon, J. Polym.

Sci,,

Polym.

Chem.

Ed., 15,

(1977). 'H NMR

-CH2N-),

(neat) 3325 Calcd

(CDC13)

3-86

S 1.56-2-4'7 (m, 4 H, -CH2-),

(t, J := 7.2 Hz, 1 H, -CH(CN)-),

(O-H), 2260

for C5H8N20:

c,

(CrN) cm.-1; mass

53.56;

2.73-3,52

(m, 2 H,

'7.18 (br, s, 1 H, OH);

spectrum

H, 7.19; N, 25.13.

m/e

112

Found:

(M').

IR

Anal.

C, 53.48;

H,

7.21; N, 25.08. mp 129-151 *C (decomp.); -LH NMR (D20) 6 2.20-3.29 11) I?: (m, 4 H, -CH2-), 3.74-4-50 (m, 2 H, -CW2N--) I 4.75 (t, J = 7.6 Hz, 1 H, -CH(C02H-) s Anal. Calcd

for C5H9NO3:

6-82, N, i0.54, 7: ‘111 NMR ! 11.O) 12) ,”

‘.

1.3)

c,

45.80;

H, 6.92; N, 10.68.

d 2:1.7-3,18 (II?,4 H, -CH2.*), 3.86

Found:

C, 45.54;

(t, J = 6.5 Hz,

H,

2 H,