Facile intramolecular cycloadditions of 2-(N-Acylamino)-1-thia-1,3-dienes

Tetrahedron Letters, Vo1.32, No.3, pp 40511(18,1991 Printed in Great Britain

0040.4039/91 $3.00 + .w Pcrgamon Press plc

FACILE INTRAMOLECULAR

CYCLOADDITIONS

OF

2.(N-ACYLAMINO)-l-THIA-1,8DIENES Ian T. Bamish,b Colin W.G. Fishwick,a*

and David R. HilLa

a The University of Leeds, School of Chemistry, b Pfizer Central Research, Sandwich,

Leeds LS2 9JT, U.K.

Kent CT13 9NJ, U.K.

Summary: 2-(N-Acylaminoj1-thia- 1,3-dienes, generated via acylation of readily available a&-unsatunited thioamides, undergo regio- and stereospecific intramolecular Diels-Alder cycloaddition with unactivated olefinic and acetylenic dienophiles to yield polycyclic dihydrothiopyrans. We have

demonstrated

chloride in the presence added

dienophiles,

N-acylation

previously

l-3 that treatment

of various a$-unsaturated

thioamides

of a variety of olefins affords good yields of dihydrothiopyrans

dimeric

systems

to yield N-acylamino

4 are obtained

These

reactions

were

1 with acetyl

3. In the absence of

rationalised

as involving

thiadiene 2 (scheme 1).

Ph

Ph AcCl

XCH=CHY

PY AC

H

3

1

Ph

S

AC 4

Scheme 1

We now report Diels-Alder

cycloaddition

dihydrothiopyrans Diels-Alder

that these

reactive to olefinic

hetereodienes and

undergo

acetylenic

stereo-

dienophiles

and

regiospecific

to yield

tricyclic

intramolecular thiopyrans

and

(scheme 2). These reactions appear to be the first reported cases4 of the intramolecular

cycloaddition

of a 1-this-I ,3-butadiene

system. 405

406

AcCl

[4+21

PY L

-1

R 6

AcCl

[4+21

PY

10

8 Scheme 2 The precursors describedI

5 and 8

are easily

amidatiotithiation

sequence.

derived from 3-(2-allyloxyphenyl)acrylic colourless with

prepared

in pyridine’2

chromatography (1.6mmol),

which

pyridine

cycloadduct

from ethanol/water

for 7hrs gave

solidified

Thus, in a typical

thioamide

on standing

(0.26ml) and acetyl chloride

are summarised

treatment

of the acid chloride

5, R=Me

(56%)

Heating

(3.2 mmol) in acetone

as a yellow a solution

of this amide

viscous

containing

(20ml) at reflux

oil after 5 , R=Me

for 16hrs afforded

on silica (scheme 2). The resu!ts of

in the table.

cycloadditions

of 6 and 9

yield(%)

thioamider

product

1

5,R=Me

7,

R=Me

88a

2

5,

R=Et

7,

R=Et

60a

3

8,

R=Me

10, R = Me

48b

entry

methyl amide as

(67%, mp, 86-87OC). Treatment

(mp, 70-72OC).

Table. Intramolecular

b:

acids5 via the previously

yielded the corresponding

7, R=Me (88%) as a yellow viscous oil after chromatography

similar cycloadditions

a:

carboxylic

experiment,

acid 5 with methylamine

needles after recrystallisation

P4Sto

from the known

These compounds gave satisfactory nmr, ir, and analytical data consistent with the proposed structures. In this case, due to the instability of this cycloadduct, structural elucidation was based on ‘H nmr, 13C nmr and ir data.

407

As indicated

in the table,

cycloadducts

which

stereochemistry

cycloadditions

possess

a m

in cycloadducts

involving

ring fusion

olefinic

geometry

dienophiles

are stereospecific

exclusively

(entries

1 and 2).

and give The

m

7 was readily apparent due to the presence of the large coupling constant

(13Hz) in the 1H nmr, between the protons at the ring junction positions 6. For cycioaddition

of dienes 6, two possible transition

(with respect to the connecting

chain between

of models of these transition

states

fused systems 7, is relatively

strain free.

infact, would interaction

nessecitate

however,

diene and dienophile)

reveals that the exo However,

a twist out of planarity

of diene and dienophile7

Interestingly

state geometries,

transition

the fully-planar of the aromatic

here as endo

ard exa

are shown below (figure). Inspection state, leading to the observed endo geometry

m

is highly strained and,

ring and thus decrease

the energy of

(figure).

for cycloaddition

involving

the acetylenic

models reveals that the aromatic ring must twist out of conjugation the approach

denoted

dienophile

( entry 3), inspection

of

with the diene system in order to allow for

of diene and dienophile7.

endo Flgure.

Clearly, acetylenes

intramolecular

Possible transition state geometries

cycloaddition

is a facile process.

of these

Further exploration

for intramolecular

thiadienes

cycloadditions.

to electronically

of the scope and potential

unactivated

olefini;

of these cycloadditions

progress in these laboratories.

Acknowledament

: We thank the SERC and Pfizer Central Research for a CASE studentship to DRH.

and is in

408

References

and notes.

1.

Bamish, I.T.;

Fishwick, C.W.G.;

Hill, D.R.; Szantay Jr., C. Tetrahedron

Lett., 1989, 30, 4449.

2.

Barnish, I.T.;

Fishwick, C.W.G.;

Hill , DR.;

Szantay Jr., C. Terraheoron,

1989, 45, 6771.

3.

Barnish, LT.;

Fishwick, C.W.G.;

Hill , DR.;

Szantay Jr., C. Tetrahedron,

1989, 45, 7898.

4.

An intramolecular Barluenga,

cycloaddition

J.; Tomas,

of a 1-thia-3aza-butadiene

M.; Ballesteros,

A.; Lopez,

system has been reported, see

L., J. Chem.

Sot.,

Chem.

1909,

Commun.,

1487.

5.

See : Cohen,

6.

Selected t H nmr data;

M.D.; Schmidt, G.M.J.; Sonntag,

7, R = Me, G(CDCl3, ppm), 7.20-6.65, 3.75, (lH, dd, Hy-7); 3.45, (lH,dd, 2.30-2.10,

(IH,

H-3); 2.05, (3H, s, C&CO-); ppm),

(4H, m, ArH); 6.05, (lH,

(3H, m, CH3CH2-,

Full details will be published

(Received

2.90-2.75,

(2H, m, Hz-2);

in UK 2X September

1990)

d, H-5); 4.30, (IH, dd, H,-7);

H-4); 2.90-2.75,

(2H, m, Hz-2); 2.30-2.10,

3.80,

(IH,

m,

1.10, (3H, t, C&&H,-). 7.25-6.85,

(4H,

m,

ArH);

(IH, d, H-5); 4.65-4.40, (3H, m, H-4, H-7); 3.05, (3H, s, C&N-);

7.

4.30, (lH, dd, Hx-7);

m, H-3); 2.00, (3H, s, C&CO-).

(IH, dd, Hy-7); 3.55-3.35,

G(CDCIa,

(4H, m, ArH); 6.10, (IH, d, J=3Hz,H-5);

J=3Hz, 13Hz, H-4); 3.00, (3H, s, C&N-);

7, R = Et, G(CDCl3, ppm), 7.15-6.75,

10,

F.I., J. Chem. Sot., 1964, 2000.

elsewhere.

6.30,

(lH,

m,

2.15, (3H, s, Cl&CO-).

H-2);

5.80,