Diastereoselective cyclisations of chiral α-acyliminium ions

Tetrahedron Letters Vol. 21, pp 1987 - 19gC @Per@%mon Press Ltd. 1980. Frinted in Srezt Britain

DIASTEREOSELECTIVE Bernard Laboratory Nieuwe Abstract:

P. Wijnberg

of Organic

Achtergracht

(R,R)-tartaric ide which

high

cyclisations respect

the naturally

ly met with For

strongly

coupling

this work

dimethyl

we decided

ether4

which

(R,R)-2,3-dimethoxy In view are expected

both

on the largely

easily

succinimide

in the NaBH4 of the latter

place

most

from

substrates igation

viz

ive manner isomer

alkene

6

to take place

via

In the

induction of the

amounted

is lost the planar

7

available

light

in the cyclisation e-acyliminium

1987

primary

recent-

materia13. acid

optically

steric

to the a-OH

leading

ring

active

w-OH 2O:l.

step

lactam

experiences

carbon

in a highly

- the

of the

latter

ion - no attempts

were

formatof

for invest atoms.

stereoselect

lb-5b --'

In view

take

two types

selected

lactams

and the

may

to the preferred

la-5a were --

proceeds

effects

closure

at the reacting

of the chiral

to approximately

have

scale5.

of earlier

la-5a --

latter

(R,R)-tartaric

to the desired

derivatives

imids

olefine

acids

of starting

Consequently side

-2c and -4c.

In the

dicarboxylic

of the imid

of asymmetry

the C5 -isomers

of -lb-5b

chirality

hindered

pure

substrates.

substituents

carbinol.

and acetylene

/H@ reduction

affording

ratios

the C5-OH

4

reduction

least

diastereomer.

of the eventual

The NaBH

the

on a practical

followed

in a-acyliminium

source

be converted

of imid OMe

cyclisation

ion of a single

active

to focus

HCOOH

easily

optically

(R,R)-dimethoxysuccinim-

and 5-hexynol

to optically

to the use of chiral

as a cheap

of the presence

into

sofar

interest

could

of Amsterdam, The Netherlands.

Z-3-hexenol

can be cyclised

occurring

considerable

converted

with

IONS1

Speckamp",

University

encountered

invited

a-ACYLIMINIUM

1018 WS Amsterdam,

acid has been

after

stereoselectivity

2

and W.N.

Chemistry,

129,

by NaBH4/ H@ reduction The

OF CHIRAL

CYCLISATIONS

being

The fact

that

assumed

carried

out

n

,eH (CH21,

x=0

X=H,OH

R,

R2

R3

la

lb

H

H

H

_2a

2b

Et

H

H

5a

3b

H

H

MQ

n=l

3a

3b

---

n=3

4a

&

---

&2c-L- 5c

Id .2d ,5d

3c 36 -a-

to isolate HCOOH lc,d --

a preferred

C5-epimers. (18 hr/r.t.)

treatment'

in nearly

ed values

OMe

the pure

quantitative

of the OMe C-C bond

substituent,

yield.

signals

not

According

the ratio

formation

albeit

of -lb afforded

from

the

to

the diastereomeric 1

H NMR

of -1c:ld was least

in a practically

estimated

hindered useful

analysis

side

manner.

mixture

of the

as 2:1, opposite

integrat-

indicating of the C4-

On the contrary ring closure of -2b (HCOOH, 18 hr/r.t.) afforded a single isomer -2c as a crystalline material in nearly quantitative yield; m.p. 78.5-80°C; IR(CHC13): 1720 and 1700 (C=O) cm -1; NMR G(CDC13): 8.02 (s, lH, CHO), 5.02 (m, H7ax W4=21

Hz), 4.11 (m, Hgeq), 3.82 (d, H3; J3 4=5.5 Hz), 3.73 (t, H4, J4 5= , I 5.5 Hz), 3.68 (s, 3H OMe), 3.46 (s, 3H OMe), 3.38 (t, H5, J5 6= 3 Hz), 2.73 (m, I 2.07 (m, H6eq). The observed J5,6 value again confirms an axial position Hgax), for the C5 -Et substituent and consequently indicates a synchronous bond formation process.

In the latter ring closure three asymmetric centres have been

introduced simultaneously with a high degree of stereoselectivity. for this

remarkable effect may be found in a destabilisation

A rationale

of the transition

state leading to g

as a consequence of increased steric interaction of -II Z-Et

and C 4-OMe groups.

The degree of stereoselectivity

of the olefin cyclisation

therefore depends on the relative position of the ring substituents with respect to the incoming nucleophile. Support for the latter assumption was found in the reaction of the acetylene derivatives -3b and -4b.

HCOOH treatment

(r.t./118 hr) of the carbinol -3b

yielded only a 1:l mixture of the starting carbinol -3b and its C5-epimer. However, at 43°C (120 hr, HCOOH) quantitative and -3d occurred.

formation of a 1:l mixture of -3c

Presumably the already low reactivity of the acetylene funct-

ion in this type of cyclisation' is even further diminished as a result of added steric factors.

The main conclusion of this experiment, however, is the lack

of preferential

formation of either -3c or 3d. On the contrary, cyclisation of 10 afforded the ketone 4~. m.p. 84-86°C; -4b (HCOOH, 3O"C, 13 days) exclusively -' NMR G(CDC13): 3.7-4.02

(m, 2H, tert NCH + NCH eq), 3.66 (s, 3H OMe), 3.44 (s,

3H OMe) 2.88 (t, J=ll

Hz, set NCH ax), 1.3-2.7 (m, 12H).

in diastereoselectivity

The dramatic change

in ring closures of -3b compared with -4b again may be

rationalized in terms of a steric repulsion between incoming acetylene moiety and C4-OMe substituent.

In view of the size of the ring to be formed the latter

interaction will be more severe in the cyclisation of -4b thus leading solely to the observed product -4c. Other N-substituents have been examined and were found to exhibit similar behaviour, as for instance in the cyclisation of 5b which gave a 1.5:1 isomer

mixture

of the C4-epimers

in the unsubstituted

series

AS a final point ness

of the C4-0

6

result

has been

found

earlier

.

of interest

on this

An analogous

and z.

substituent

Studies

reaction.

E

it is anticipated

may

further

aspect

increase

are currently

that

enhancing

the bulky-

the stereoselectivity

of the

in progress.

References 1.

Part

of the

forthcoming

Ph.D.thesis

of B.P.

Wijnberg,

University

of

Amsterdam. 2.

Speckamp,

W.N.

Conferences Excerpta

Hoechst",

Medica

3a. D. Seebach,

Act.,

4.

52,

imid b. C.R.

Young,

7.

J. Dijkink,

8.

The

Bartmann

Products

-Workshop

and Winterfeldt,

Eds.

1979. B. Bastani,

W. Langer,

G. Grass,

H. Daum,

C. Niissler, Hoc-An

Oei,

H. Dijrr, M. Schmidt,

(1977):

Eva-Maria

Wilka,

P. Hilvert,

E. Brunner,

Helv.Chim.

(1979).

H. Schenker,

Helv.Chim.Act.,

of the amide

J.Chem.Soc.,

Schoemaker, H.E.

cyclisation

homogeneous

acid

5b

22,

at 200°C

754

(1970).

for several

minutes

Lett.,

939

gave

the

1228

(1914).

W.N.

Speckamp,

Tetrahedron,

Schoemaker,

W.N.

Speckamp,

Tetrahedron

experiments

were

carried

out with

zi,

163

Lett.,

(1978).

4043

(1975).

chromatographically

samples. 3. Dijkink,

H.E.

Schoemaker,

W.N.

Speckamp,

(1977).

Schoemaker,

(Received

102, ---

J. Dijkink,

Tj. Boer-Terpstra,

H.E.

of Natural

in ca. 60% yield;

H.E.

10.

2695

heating

6.

9.

301

G. Grass,

I. Felner,

5a. Direct

$2,

Synthesis

p.50-62,

Kalinowski,

V. Ehrig,

Helv.Chim.Act., b. D. Seebach,

Vo1.7,

(Elsevier)

H.O.

DuPrecz,

N.P.

"Stereoselective

Ph.D.thesis,

m UK 28 February 1980)

University

++++++

of Amsterdam

(1979).

Tetrahedron