Carbocycles from carbohydrates: a free radical route to aminocyclitol derivatives

OM-4039/91 %3.W+ .oo Pcrgamon Press plc

Tetrahedron Lelkrs. V01.32, No.44. pp 6437.6440, 1991 Printi in Great Britain

CARROCYCLES

FROM CARROHYDRATES: TO AMINOCYCLITOL

Jose Marco-Contelles,*

A FREE RADICAL

DERIVATIVES

Luis Martinez,

Carmen

Pozuelo,

ROUTE

Angeles

Martinez-Grau,

and M.L. Jimeno.

Institute de Quirnica Otgbnica (CSIC); Juan de la Ciervq 3. 28006Madrid,

Spain.

Abstract: Some derivatives of (lRJR,3R,4S,W) and (1R,2R,3R,4R,5S)-5-amino-l,2,3,4-cyclohexanetetrol been synthesized from acyclic carbohydrate intermediates via 6-exo free radical cyclization.

5-Amino-1,2,3,4eyclohexanetetrols Methods

for

the

transformation nitroalkane method

synthesis

methodology.”

for the synthesis

the

in the synthesis

compounds

of this

intramolecular

nitrone

of aminocyclitols.1~2~”

type

are

limited

cycloaddition’

In the last years the free radical7 route has proven

of carbocycles

of acyclic carbohydrate

intermediates pure

of 6-deoxy-5-enopyranosides,4 cyclization

cyclization

are valuable

of enantiomerically

have

from carbohydrates.

intermediates

* To our knowledge

has not been

explored

to

the

and

the

to be an efficient

the 6-exo free radical

or has failed

to yield cyclized

products.’ In

this

communication

we

5-amino-1,2,3,4qclohexanetetrols The strategy formation

is shown

via

in Scheme

giving intermediate

The

radical

ti -D-glucofuranose” intermediates (see Table). established

report

a

new

and

simple

6-exo free radical cyclization

I; the protected

3 ‘r have

been

prepared

from

gave compounds by analysis

4 and

5 (Scheme

stereochemistry

of their ‘H-NMR

J 5 bax= 12.4 Hz,

II)

yield and

oxime

ether

hydride.‘O

a

cyclization’4 good

in the major

for major 4a, for instance, is reasonable

of

derivatives.

and

by tributyltin

The

in moderate

is what we is in a

derivatives

6-bromo-6-deoxy-1,20isopropylidene

at the new stereocenter spectra;

chiral

bromination

mediated

and 3,5-di-O-benzyl-6-O-trityl~-D-glucofuranose.’3

The absolute

to

of acyclic carbohydrate

1 undergoes

lactol

2 ready for free radical cyclization

precursors

route

these

diastereoselectivity isomers

4 has been

sH, 3.25 (ddd, Jds= 10 Hz,

substituent

in this

of

at C-5,

of compounds.

2,3-O-isopropylidenen-D-mannofuranose” in 50 % In the

‘H-NMR

7 showed

6Hti0 2.16

J tiq,1= appears with

H at 3.19 ppm as a

a vicinal coupling at C-5, being 6437

constant

is consistent in

chair-like

conformation.

6438

I

Scheme

2

1

Scheme

II

Br

RIO,_ %

RlO

G

(B-Bu)3SnIl -NwOR--------------_)

R2011111

A

R20;jQN”OR

r,:;Q;;HOR

.;$

2

‘OR2

RIO

2

5

3

Table. Tin Hvdride Mediated Cvclization of Oxime Ethers substrate entry

Rl

1

a AC

R2 AC

2

b Bz

3

(3)

product ratios R

r/sa(b)

yield(%)c

Bn

83/17 (only p)

BZ

Bn

75/25 (80:20)

55

c Bz

Bz

Me

73/27 (only 8)

50

4

dBn

H

Bn

80/20 (94:6)

40

5

e Bn

52

(a)

AC Bn 78/22 (89:ll) 42 Product ratios computed from NMR analysis of crude mixtures.

(b)

Product

ratios

after

purification,

cyclized product. Scheme

Ill

(c)

Total

yield

of

6439

In Scheme substrates

3.

interaction

between

equilibrium influence

IV we show a possible Assuming

model for the stereochemical

a chair-like

the substituent

to conformer

i leading

of stereoelectronic

conformation

for

these

at C-S and the oxime to compounds

ether

4 predominantly;

effects of the atyl esters or ethers

results carbon at C-l

obtained

in the cyclization

centered

radicals,16

the

of

steric

(sugar

numbering)

drives

the

in this picture

we cannot

exclude

the

functional

groups.8b

IV

Scheme

-.qNHoR H 4

b

H

-0 + NHOR 5

ii

In

summary,

a stereoselective

5-amino-1,2,3,4cyclohexanetetrols for further ratios

development.

of the cyclized

The moderate products

examining

other carbohydrate

References

and Notes

1. Umezawa, 2. Balci,

A.K.

for

the

yields in the cyclization

precursors

Y.; Secen,

H.

preparation

has been achieved.

and the easy availability and will report

S. Adv. Carhohydr. Gem.

M.; Stbeyaz,

3. Mallams,

method derivatives

Biachem.,

Tetrahedron,

These

of

is overcomed

of the radical these studies

enantiomerically

are useful chiral building

pure blocks

by the good to excellent

precursors.

We

are currently

in due course.

1974, 30, 111. 1990, 46, 3715.

In Carbohydrate Chemistry, Kennedy,

J.F.

Ed., Clarendon

Press,

Oxford,

1988;

pp 73-133. 4. (a) Ferrier,

R.J. J. Chem. Sot., Perkin Trans 1,1979,

1455. (b) Semeria,

D.; Philippe,

M.; Delaumeny,

6440

A.M.; Gero, S.D. Synthesis, 1983,710.

J.M.; Sepulchre, 5. (a) Bernet,

B.; Vasella,

A. Hefv. Chim. Acta, 1979,62,

1990 (b) Shing, K.M.T., Elsly, D.A.; Gillhouley,

J.G. .I. Chem. Sot., Chem. Commun., 1989,128O. 6. (a) Grosheintz,

J.M.; Fischer,

Am. Chem. Sot., 1948, 70, 1476. (b) Bauer, H.H.;

H.O.L.J.

Siemsen,

L.

Astles, O.J. Carbohydr. Res., 1986,156, 247. 7. (a) Giese, B. Radicals in Organic Synthesis: Formation T.V. J. Am.

Chem.,l985,

50,546.

RajanBabu, Gaudino,

T.V.;

9. Yeung, B.-W.A.; 10. Bartlett,

P.A.;

(c) Nugent,

Fukunaga, Alonso,

and

experiment,

AIBN

10% aqueous

was separated,

dried

dimerized Selected

products.

carbohydrate

3 (2.5-3.5 mmol; obtained

in benzene

under

(t. J=lO

potassium

fluoride

cyclization

products

Hz, IH, H-4),

12.4 and 14.5 Hz, H-6ax).

solution

and

Flash chromatography

In the

data.

12.4 and 4.2 Hz,

of

incompletely

4a: mp llh-118°C;

compound identified

5.44 (q, J=3.1

2.10,

13C-NMR

1.90 (ddd,

3.19 (m, lH,

J5,6ax=9.8

16. Hannesian,

with tributyltin

was removed stirred

hydride

overnight.

The

3 and 6 small were

also

present

Hz, lH, H-l),

2.09, 2.01,

(20 MHz, CDC13) 6:

H-5), 2.16

Hz, J1,6eq=8

H-l,

D.S.; Beaulieu,

(Received in UK 29 August 1991)

(<

10%) of

(300 MHz,

Hz, lH, H-3), 5.21

H-6eq),

3.25 (ddd,

1.88 (ddd, J=3.1,

170.23, 170.05, 169.97, 169.91 (OCOCH,),

76.99 (GCH2CgH5),

5.30-5.20 ( m, 2H,

71.87, 71.72, 71.20, 67.82 (C-l, 2, 3, 4) MS (70 eV) m/z:

H-2),

4.70

438 (M+ 1, 8), 378 (300 MHz, CDCI,)

(s, 2H, OCH2C6H5),

(dt, J6eq 1 =Jbeq 5=5.4 Hz, J6eq 6ax’ 13.6 Hz, lH,

Hz, Jheq,6ax=

phase

mixtures

in the reaction.

‘H-NMR

5.35 (t, J=lO

1.98 (s,s,s,s, OCOCH3,

diluted

organic

acetate

amounts

that

(2.4 equiv)

and the residue

using hexane-ethyl

13.8 Hz, lH,

H&ax).

K.; Wolf, A. Chem. Ber., 1927,60, 1232. S.; Dhanoa,

radical

ofsyn +anti isomers

as mixtures

l), 269 (17), 267 (13), 91 (100) 43 (30).

15. Freudenberg,

of the

227.

77 (3), 43 (14). 7: oil; [a12’D + 2.7” & 2.2, CHC13) ‘H-NMR

6: 7.40-7.27 (m, 5H, aromatic),

(M+-15,

synthesis

4.92 (dd, J= 10 and 3.1 Hz, lH, H-2), 4.61 (s, 211, OCH2C6H5), lH, H-5)

139.14, 128.67, 128.55, 128.14 (aromatic),

2H, H-3, H-4),

The

[alz5 D -72” & 4.5, CHCI,).

56.87 (C-5), 29.78 (C-6), 21.01, 20.84, 20.75, 20.06 (OCOCH3). (1), 287 (2), 91 (loo),

data.

(0.01 M), were treated

argon for 3 h. The solvent

CDC13) 6: 7.34-7.26 (m, 5H, aromatic), J=lO,

and spectroscopic

H. Carbohydr. Res., 1978,6.5, 132.

and evaporated.

spectroscopic

8561. (d)

Chem., 1989,8,413.

B. .I. Carbohydrate

A.K.M. Methods Carbohydr. Chem., 1980,8,

compounds

(cat.) at reflux,

desired

L.M. J. 0%.

1988,110,

Sot.,

T.V. .I. 0%. Chem., 1988,_53,4522.

3102. (f) RajanBahu,

good analytical

dissolved

with ether plus gave the

C.S.; Thomasco,

T.V. .I. Am. Chem.

elsewhere.

W.; Weidmann,

we could not separate)

Press;

K.L.; Ting, P.C. J. Am. Chem. Soc.,l988,1~0, 1633.

R.L.; Anisuzzaman,

74. In a typical

Pergamon

G.S. J. Am. Chem. SOL, 1989, 111, 1759. (e) Wilcox, C.S.;

T.; Reddy,

showed

13. Dax, K.; Wolflehner,

609. (b) Wilcox,

RajanBahu,

Sot., 1986,10&

will be detailed

12. Whistler,

W.A.;

R.; Vite, G.; Fraser-Reid,

McLaren,

11. All new compounds precursors

SOL, 1987,119,

Chem.

J.J. J. Am. Gem.

Bonds,

D.P. Synthesis 1989, Part 1, p.417; Part 2, p. 489.

New York, 1986. (b) Curran, 8. (a) RajanBabu,

of Carbon-Carbon

P. Can. .I. Chem., 1987,6.5, 1859.

4.22 (m, H-6eq),

MS (70 eV) m/z:

378