B u l l . SOC. Chim. Belg . vo1.95/n011/1586

Lecture given a t the X I I t h European Colloquium on Heterocyclic Chemistry, University of Reims Champagne-Ardenne, France, September 29 , 30, October 1 , 1986

SOME SYNTHETIC APPLICATIONS OF N-AMINOHETEROCYCLES :

PREPARATION OF BRIDGEHEAD-NITROGEN HETEROCYCLES

Pedro Molina Departamento d e Quimica Organica , F a c u l t a d d e C i e n c i a s Quimicas y Matemat icas ,

Un ive r s idad d e Murcia, 30001 Murcia, Spa in

Some a s p e c t s of t h e chemis t ry of t h e h e t e r o a r o m a t i c N-imines and t h e i r

p r o t o n a t e d compounds N-arninoazonium sa l t s have been comprehens ive ly reviewed' '

W e wish t o d e s c r i b e now t h e use o f N-aminoheterocycles i n t h e p r e p a r a t i o n o f

b r idgehead-n i t rogen h e t e r o c y c l e s . I n a l l c a s e s , t h e s t a r t i n g N-aminoheterocy- c l e i s found t o b e c o n v e n i e n t l y f u n c t i o n a l i z e d i n a t l e a s t one of t h e a d j a c e n t

p o s i t i o n s of t h e e n d o c y c l i c n i t r o g e n atom. I n some c a s e s , t h e h e t e r o a r o m a t i c

r i n g a p p e a r s b i - f u n c t i o n a l i z e d , as i n t h e c a s e o f t h e 1 , 2 , 4 - t r i a z i n e r i n g , where i n a l l s t u d i e d c a s e s p o s i t i o n 5 i s occupied by a c a r b o n y l g roup , p o s i t i o n

3 meanwhile b e a r i n g a t h i o l , a l k y l t h i o or a ry l amino group. A s imi la r s i t u a t i o n appea r s i n t h e 1 , 2 , 4 - t r i a z o l e r i n g , where p o s i t i o n 5 i s sometimes occupied by

a c a r b o n y l , t h i o c a r b o n y l o r a l k y l t h i o group.

lo x=o 2 0 X=SH l b X=S 2b X=SCHa

2 c X=NHAr

I1

5

SCHEME 1

The r e a c t i o n s s t u d i e d have been done wi th t h e f o l l o w i n g r e a g e n t s :

1. NITRILES. Add i t ion o f t h e N-amino group on t h e CN t r i p l e bond l e a d s t o

h e t e r o a r y l aminides which under r e a c t i o n c o n d i t i o n s undergo c y c l i z a t i o n by a t - t a c k o f t h e aminide group on t h e f u n c t i o n a l i z e d p o s i t i o n o f t h e h e t e r o a r o m a t i c

r i n g t o g i v e fused h e t e r o c y c l e s . Sometimes b e f o r e t h e c y c l i z a t i o n s t e p it i s necessa ry t o a c t i v a t e t h e h e t e r o a r o m a t i c r i n g towards a n u c l e o p h i l i c a t t a c k .

- 9 7 3 -

Usual ly t h i s a c t i v a t i o n is made by q u a t e r n i z a t i o n . Th i s i s a good method f o r t h e p r e p a r a t i o n of f u s e d 1 , 2 , 4 - t r i a z o l e s .

SCHEME 2

Examples of t h i s t y p e of r e a c t i o n s are : The N-aminoheterocycle &, r e a c t s w i th n i t r i l e s under b a s i c c o n d i t i o n s t o g i v e

l 1 2 , 4 - t r i a z o 1 0 (1,5-g) p y r i d i n e s 2 i n good y i e l d s 3 ( 6 4 - 7 9 % ) . W e have a l so found

t h a t compound 3 r e a c t s w i th e t h y l benz imida te s under similar c o n d i t i o n s t o

g i v e 2 i n modera te y i e l d s ( 4 0 - 5 0 8 ) . The method appea r s t o be q u i t e g e n e r a l f o r a romat i c and he te roa romat i c series. Y i e l d s a r e h igh b o t h when t h e a romat i c

r i n g i s s u b s t i t u t e d by e l e c t r o n - d o n a t i n g and e l ec t ron -wi thd rawing groups .

However, a t t e m p t s w i t h f u n c t i o n a l l y s u b s t i t u t e d a l i p h a t i c and u n s a t u r a t e d n i - t r i l e s f a i l e d t o g i v e 2. The p r i n c i p a l advan tages of t h i s p rocedure a r e t h e

h igh y i e l d s , t h e one - s t ep p rocedure , and t h e a v a i l a b i l i t y of s t a r t i n g materials. P r i n c i p a l d i s a d v a n t a g e s a r e slow r e a c t i o n r a t e s abd t h e a p p l i c a b i l i t y t o aroma-

t i c and he te roa romat i c n i t r i l e s o n l y .

Ph Ph

Ph Qo + R - C N KOC4Hp-1

la 5

SCHEME 3

- 9 7 4 -

The N-aminoheterocycle s, r e a c t s w i t h a romat i c n i t r i l e s i n t h e p re sence o f

po tass ium t -bu tox ide f o r 2 4 h t o g i v e b i c y c l i c sa l t s which undergo e l e c t r o p h i -

l i c a t t a c k a t t h e p o s i t i o n 1 by t h e a c t i o n of methyl i o d i d e t o g i v e 1 , 2 , 4 - triazolo(4,3-b)-1,2,4-triazoles 2 i n good y i e l d s 4 (59 -82%) . r o u t e t o t r i a z o l o - t r i a z o l e s 6 i s based on t h e r e a c t i o n o f

t h e p r e s e n c e of po tass ium t -bu tox ide i n t - b u t a n o l f o r 2-3 h t o g i v e amidino-

t r i a z o l e s a s c r y s t a l l i n e s o l i d s i n good y i e l d s . S e q u e n t i a l t r e a t m e n t o f amidi -

n o t r i a z o l e s w i t h methyl i o d i d e and potass ium t - b u t o x i d e l e a d s t o 6 i n modera te

y i e l d s .

An a l t e r n a t i v e

w i t h n i t r i l e s i n

Ar

6

SCHEME 4

The 4 - a m i n o - l - m e t h y l - 3 - m e t h y l t h i o - l ~ - l , 2 , 4 - t r i a z o l e - 5 ( 4 H ) - t h i o n e r e a c t s w i t h

a romat i c n i t r i l e s i n b a s i c medium t o g i v e t h e monocyclic s a l t 8 i n modera te

y i e l d s . When a h y d r o a l c o h o l i c s o l u t i o n of t h i s po tass ium s a l t i s t r e a t e d w i t h

methyl i o d i d e a t room t empera tu re t h e new mesoionic compound 2 d e r i v e d from

1,2,4-triazolo(4,3-~)-1,2,4-triazole r i n g system i s i s o l a t e d i n good y i e l d s

(57-91%). N i t rogens N - 1 , N-5 and N - 7 cou ld a l s o have r e a c t e d wi th methyl i o d i -

de , b u t no N,N'-dimethyl d e r i v a t i v e has been i s o l a t e d . The h i g h r e a c t i v i t y

of t h e s u l f u r atom i n m e r c a p t o t r i a z o l e s could e x p l a i n t h e fo rma t ion o f t h e me- s o i o n i c compound, bu t having c a r r i e d o u t t h e r e a c t i o n on s a l t it canno t be ex-

c luded t h e p o s s i b i l i t y t h a t S-methyla t ion p recedes t h e c y c l i z a t i o n s t e p . The

s t r u c t u r e of 9 has been e s t a b l i s h e d throughout a c a r e f u l carbon-13 and X-ray

c r y s t a l l o g r a p h y . The S-methyl group i s d i r e c t e d towards t h e f u s i o n of t h e

five-membered r i n g s a t +/- syn confo rma t ion , t h e azapen ta l ene m o i e t i e s have

t h e f i r s t atoms of t h e s u b s t i t u e n t s on i t s p l a n e and t h e 6-phenyl r i n g make an

a n g l e o f - 2 6 . 6 and -4.4' wi th i t , i n t h e two independent molecu le s r e s p e c t i v e -

l y . From t h e r e l a t i o n s h i p between bond l e n g t h s and bond o r d e r s , i t can be de-

duced t h a t a c a n o n i c a l form as t h e r e p r e s e n t e d d e s c r i b e s a c c u r a t e l y t h e elec- t r o n i c s t r u c t u r e o f 2. When i n compound 2. t h e t h i o c a r b o n y l group was r e p l a c e s by a ca rbony l group,

t h e r e s u l t i n g N-aminoheterocycle r e a c t s w i t h n i t r i l e s under s imi la r r e a c - t i o n c o n d i t i o n s t o g i v e b i c y c l i c s a l t s 11, which do n o t r e a c t w i t h methyl i o -

d i d e . P r o t o n a t i o n o f 11 l e a d s t o t h e n e u t r a l 1,2,4-triazol0(4,3-~?)-1,2,4- t r i a z o l e s 12 (70 -83%) . of t h e mesoionic compounds 9 .

5

These compounds are a l s o p repa red by b a s i c h y d r o l y s i s

- 9 7 5 -

9

SCHEME 5

SCHEME 6

2. ISOTIOCYANATES. Some N-aminoheterocycles react with isothiocyanates to give N-heteroaryl thioureas which undergo ring-closure either by heating or in the presence of base to give, depending upon the nature of the substituent on the heteroaromatic ring, fused 1,3,4-thiadiazolo or 1,2,4-triazoles.

.. . . I \ I \

I $

;.-. ,~ , I

, 1

''\N/& R- NCS ' . t N A X I I NH2 HNYNH-R

S // 1x.i

- 9 7 6 -

The starting N-aminoheterocycles bearing a thiocarbonyl group or derivative. In some cases, the thiocarbonyl group exhibits annular thione-thiol tautomerism, in other cases such possibility does not exist and finally N-aminoazonium slats bearing a methylthio group on the heteroaromatic ring have been used. N-Aminoheterocycles carrying a potential thiol group in an adjacent position to the endocyclic nitrogen atom, react with aryl isothiocyanates under neutral conditions to give fused 1,3,4-thiadiazoles.

H3y3SH -- R-NCS/DMF H 3 ~ ~ ~ ~ s REF. 6

I A I NHZ =A N H -R

SCHEME 8

When the N-aminoheterocycle bearing a thiocarbonyl group and there is no pos-

sibility of annular thione-thiol tautomerism, its reaction with isothiocyanates in the presence of base leads to fused 1,2,4-triazoles which display mesoionic character .

REF. 8 R-NCS S Et,N I

NHz

SCHEME 9

Similar results can be achieved when N-aminoazonium salts are used as starting materials. Thus, l-amino-2-methylthio-4,6-diphenylpyridinium cation 13, reacts with isothiocyanates in acetonitrile in the presence of equimolecular amounts of triethylamine to give 1 , 3 , 4 - t h i a d i a z o l o ( 3 , 2 - a ) p y r i d i n i u m salts 14. However,

- 9 1 1 -

when the reaction is carried out in dimethylformamide at room temperature in the presence of an excess of thiethylamine, the mesoionic compounds 1,3,4- triazolo (3,2-2) pyridylium-2-thiolate 15 are isolated”. diazolopyridinium into the mesoionic compound is achieved in almost quantita- tive yield by treatment with triethylamine in dimethylformamide at room tempe- rature. We believe that this transformation involves a mesoionic-2-aminide as intermediate which under reaction conditions rearranges to the mesoionic-2- thiolate.

The conversion thia-

Ph

I 15

13

DMF/EI,N

14

SCHEME 10

Similarly, 4-amino-l-methyl-3,5-bis(methylthio)-l,2,4-triazolium iodide 16, reacts with aryl isothiocyanates in dimethylformamide in the presence of triethylamine at room temperature for 2 4 h to yield the new mesoionic compounds derived from the 1,2,4-triazol0(4,3-~)-1,2,4-triazole ring system 5 as crys- talline solids in high yields’’ However, when the reaction is car- ried out under ultrasonic irradiation, the reaction is completed in only 6 h. Compounds g react with methyl iodide in dry benzene at room temperature to give the corresponding methiodides, which react with malononitrile under non- hydrolytic solid-liquid fase transfer catalysis using KF(base)/TEBA(catalyst) to give functionalized heterocyclic enamines which by action of hydrochloric acid undergo hydrolytic cleavage followed by cyclization to give pyrazolo(5,l- - c)-1,2,4-triazole.

( 7 0 - 8 0 % ) .

16 17

SCHEME 11

- 978 -

3. PHENACYL BROMIDES. Several N-arninoheterocycles undergo cyclocondensation reaction by action of phenacyl bromides to give a new six-membered ring such as 1,3,4-oxadiazine or 1,3,4-thiadiazine. In the latter case the sulfur extru- sion allows the preparation of fused pyrazoles.

R x = 0. s

SCHEME 12

l-Amino-4,6-diphenylpyridine-2-thlone 2, reacts with phenacyl bromides to give pyrido(2,1-f)-1,3,4-thiadiazinium - bromides 18 in high yields ( 7 5 - 9 8 % ) . When ethanolic solutions of the salts g are treated with triethylamine, the colour of the reaction mixture turned deep red indicating the formation of the peri- pheral ylids 19, which are isolated as crystalline solids in high yields. Although the mass spectra of 19 clearly show the toeliminate sulfur, extrusion of sulfur from does not occur at temperatures up to 200' even in the presence of triphenylphosphine or triethyl phosphite which normally promote this type of reaction in other cases. However, compounds - 19 react with m-chloroperbenzoic acid in chloroform at reflux temperature to give the corresponding pyrazolo(l,5-a)pyridines 20 in moderate yields .

ability of these heterocycles

12

l b Ar

18

Ar 19 20

SCHEME 13

- 9 7 9 -

This approach f o r t h e p r e p a r a t i o n of fused p y r a z o l e s , based on t h e s u l f u r

e x t r u s i o n from fused 1 , 3 , 4 - t h i a d i a z i n e s d e r i v a t i v e s , has been a p p l i e d i n t o t h e

s y n t h e s i s of o t h e r w i s e n o t r e a d i l y a v a i l a b l e pyrazolo(5,1-~)-1,2,4-triazole r i n g sys tem 21 : 4-Amino-l-methyl-1~-1,2,4-triazole-5(4H)-thiones 3 - s u b s t i t u t e d

r e a c t w i t h a-bromopropiophenone t o g i v e b i c y c l i c s a l t s i n good y i e l d s (65 -75%) ,

which undergo s u l f u r e x t r u s i o n by a c t i o n of t r i e t h y l a m i n e t o y i e l d t h e c o r r e s -

ponding pyrazolo(5,1-~)-1,2,4-triazoles On t h e o t h e r hand, t h e r e a c t i o n w i t h phenacyl bromides l e a d s t o t h e expec ted

b i c y c l i c s a l t s which b e t r e a t m e n t w i t h equ imolecu la r amounts o f t r i e t h y l a m i n e

y i e l d two compounds none be ing t h e pyrazolo(5,1-~)-1,2,4-triazole. The major

p roduc t h a s a complex s t r u c t u r e wi th an a z a p e n t a l e n e moie ty whereas t h e minor

product i s a symmetr ica l d i s u l f i d e w i t h two a z a p e n t a l e n e moiet ies . To i d e n t i f y

unambiguously bo th compounds X-ray s t r u c t u r e d e t e r m i n a t i o n s have been per formed.

i n good y i e l d s 1 3 (50 -65%) .

21

SCHEME 1 4

4. ACTIVATED METHYLENE GROUPS. T h i s t y p e of r e a g e n t has been used towards s e v e r a l N-aminoazonium s a l t s such as pyr id in ium and 1 , 2 , 4 - t r i a z o l i u m c a t i o n s .

The r e a c t i o n i n v o l v e s n u c l e o p h i l i c a t t a c k of t h e methylene group on p o s i t i o n 2 of t h e he t e roa romat i c r i n g fo l lowed by a d d i t i o n of t h e N-amino group on one of t h e a c t i v a t i n g groups of t h e r e a g e n t . Th i s method i s a p p l i c a b l e f o r t h e p re -

p a r a t i o n of f u n c t i o n a l i z e d fused p y r a z o l e s .

Z ' z C N , Y 1 NH? Z':COR, Y = R

SCHEME 15

- 980 -

N-Aminoazonium cation 13, reacts with acetonitriles activated by another elec- tron-donating group'l or l13-dicarbonyl compounds15 to give the corresponding pyrazolo(l,5-a)pyridines z in 5 2 - 8 4 % yield. The best results are obtained when the reaction is carried out in dimethylformamide in the presence of potas- sium t-butoxide or sodium methoxide. Of note are the good yields of pure isolated product and furthermore the isolation of products is easily accomplis- hed by removal of soivent.

22

base

SCHEME 16

This method of preparation of fused pyrazoles has also been used when the star- ting N-aminoazonium salts is a five-membered ring. Thus, 1,2,4-triazolium cat- ion 2 reacts with activated acetonitriles in the presence of pyrrolidine to give functionalized enamines 3, which are isolated as crystalline solids in high yields. When compounds 23 are treated with sodium methoxide the corres- ponding pyrazolo(5,1-~)-1,2,4-triazoles 2 are isolated in very low yields. Nevertheless, they undergo cyclization by action of dry hydrogen chloride at room temperature for a short period of time to give 24 in good yields16 (73- 838).

23 16

24

SCHEME 1 7

- 9 8 1 -

5. HETEROCUMULENES AND ACYL CHLORIDES. I t i s w e l l known t h a t iminophosphoranes

r e a c t w i th carbon d i o x i d e , carbon d i s u l f i d e , i s o t h i o c y a n a t e s ( i s o c y a n a t e s ) and

a c y l c h l o r i d e s t o g i v e i s o c y a n a t e s , i s o t h i o c y a n a t e s , ca rbod i imides and imidoyl

c h l o r i d e s r e s p e c t i v e l y . O u r approach t o a gene ra l s y n t h e s i s of fu sed mesoionic compounds a s r e p r e s e n t e d

i s based on t h e understanding t h a t t h e va l ence t a u t o m e r i c i s o c y a n a t e , i s o t h i o -

cyana te and carbodi imide could c y c l i s e spontaneously. The problem of s y n t h e i s

i s , t h e r e f o r e , reduced t o use a r o u t e t o i s o c y a n a t e s , i s o t h i o c y a n a t e s and c a r -

bodi imides from iminophosphoranes. S i m i l a r l y , r e a c t i o n of a c y l c h l o r i d e s wi th

iminophosphoranes l e a d s t o t h e h i g h l y r e a c t i v e i n t e r m e d i a t e s imidoyl c h l o r i d e s

which undergo r i n g - c l o s u r e spontaneously t o a n e u t r a l o r c a t i o n i c fused h e t e -

rocyc le .

r -.

Nf&

N=C=Y I

SCHEME 18

BY t h i s method and u s i n g t h e iminophosphorane d e r i v e d from 1-amino-4,b-diphe-

nyl-2-pyridone 2 ( X = O ) , mesoionic compounds d e r i v e d from 1 ,3 ,4 -oxad iazo lo (3 ,2

- a ) p y r i d i n e - r i n g system : 2-o la t e g ( X = O ) , 2 - t h i o l a t e 21 ( X = O ) and 2-aminide

- 28 (X=O) , have been ob ta ined8 .

d e r i v e d from i t s t h i o analog 2 ( X i s ) , mesoionic compounds d e r i v e d from 1 , 3 , 4 - t h i a d i a z o l o ( 3 , 2 - g ) p y r i d i n e r i n g system : 2 - o l a t e g ( X = S ) , 2 - t h i o l a t e 27 ( X = S )

and 2-aminide 2 ( X = S ) , have been prepared . The r e a g e n t which a l low t h e p r e p a r a t i o n of t h e s e types of mesoionic compounds

a r e t h e fo l lowing : carbon d i o x i d e , carbon d i s u l f i d e and a r y l i so th iocyana ted

( i s o c y a n a t e s ) . A l l t h e reactions are c a r r i e d o u t a t room t empera tu re i n d ry

benzene. We b e l i e v e t h a t t h e mechanism o f t h e s e conve r s ion i n v o l v e s t h e i n i - t i a l aza -Wi t t ig r e a c t i o n t o g i v e t h e open-chain va l ence tautomer which undergo

c y c l i z a t i o n t o t h e fused mesoionid compound.

I n a s i m i l a r manner, from iminophosphorane

8

- 9 8 2 -

27 25 26

I Ar-NCS

t Ph

2 8

SCHEME 19

Similarly, iminophosphorane derived from 2 reacts with acyl isothiocyanates to give mesoionic compounds derived from the 1,2,4-triazolo(3,4-t)-1,3,4-thiadia- zole ring system 2 in high yields17.

2 9

SCHEME 20

Although N-aminoheterocycles 1 and 2 show structural similarity, their imino- phosphoranes exhibit striking differences in their reactions toward aryl iso- cyanates. Iminophosphorane derived from 2 reacts with aromatic isocyanates in dry benzene at room temperature to give 1,3-diaryl-1,3-diazetidine-2,4- diimines 2 in high yields1*. throughout a careful carbon-I3 NMR study and X-ray crystallography. The struc- ture shows two important facts : a) the diazetidine ring is symmetrically sub- stituted and b) both heterocyclic ring are tourned towards one aryl substituent (Z,Z-configuration). This explain the H NMR spectra, for instance that of 2 (Ar= 4-C1-C6H4) recorded at 300 MHz in CDC13 shows two AA'BB' system, the most remarkable feature in the C-13 NMR spectrum is the great difference in chemical shifts between carbons orto to the diazetidine ring in p-chlorophenyl substi- tuents (119.4 and 129.1 or 129.7). The formation of diazetidine 2 presumably involves an initial aza-Wittiq reac- tion between iminophosphorane and the isocyanate to give a carbodiimide which under reaction conditions undergoes a [ r l i + fl;] cycloaddition to give 2. The formation of 1,3-diazetidine-2,4-diimines by dimerization of carbodiimides

The structure of 2 have been established

- 9 8 3 -

30

SCHEME 21

is a case of pericyclic reaction of cumulenes. It is well known for a long time (for instance, the dimerization of diphenylcarbodiimide) but all examples concern symmetrical compounds. Thus, there is no problem of regioselectivity. Moreover, no X-ray structure of 1,3-diazetidine-2,4-diimines having been deter- mined, the configuration of the imino group was unknown. On the other hand, iminophosphorane derived from &, reacts with aromatic iso- cyanates in dry benzene at room temperature to give 1,2,4-triazol0(5,1-~)-1,2, 4-triazines 2 in very good yields''. triazines 31 are : unambiguous position of the aryl substituents, high yields, mild and convenient reaction conditions and general availability of starting materials. This iminophosphorane also reacts with acyl chlorides to give 1,2,4-triazolo(5,1-g)-1,2,4-triazines 32 in excellent yields

Advantages of this route to triazolo-

18 .

31

SCHEME 22

- 9 8 4 -

32

REFERENCES 1. H . J . Timpe, Adv. Heterocycl. Chem., 17, 2 1 3 ( 1 9 7 4 ) . 2 . Y. Tamura and M. Ikeda, Adv. Heterocycl. Chem., 29, 7 1 ( 1 9 8 1 ) . 3. P . Molina, A. Tarraga and C. Martinez, Synthesis, 974 ( 1 9 8 2 ) . 4. P . Molina, M. Alajarin and M.J. Vilaplana, Synthesis, 415 ( 1 9 8 3 ) . 5. M. Alajarin, P . Molina, A. Tarraga, t1.J. Vilaplana, M.C. Foces-Foces, F.

Hernandez Cano, R.M. Claramunt and J. Elguero, Bull. Chem. SOC. Jpn., 5 8 , 735 ( 1 9 8 5 ) .

6 . P. Molina, M. 7. P . Molina and 8. P . Molina, M.

I, 3 5 1 ( 1 9 8 2 ) 9. P. Molina, A.

( 1 9 8 4 ) . 10. P. Molina. M.

Alajarin and R. Benzal, Synthesis, 759 ( 1 9 8 3 ) . A. Tarraga, Synthesis, 4 1 1 ( 1 9 8 3 ) . Alajarin, A. Arques and R. Benzal, J . Chem. SOC. Perkin Trans

Arques, I. Cartagena and M.V. Valcarcel, Synthesis, 8 8 1

Alaiarin. A . Araues. R. Benzal, H. Hernandez, Tetrahedron

11.

12. 13 .

14.

1 5 . 16 . 17. 18.

19 .

Lett. 3523 (1983) ; J. Chem. S&. Perkin Trans I, 1 8 9 1 ( 1 9 8 4 ) . P . Molina, A. Lorenzo, R.M. Claramunt and J. Elguero, Tetrahedron Lett., 5427 ( 1 9 8 4 ) ; Tetrahedron 42, 2 1 2 1 ( 1 9 8 6 ) . P . Molina, A. Arques and A. Ferao, Synthesis, 645 ( 1 9 8 2 ) . M. Alajarin, P . Molina, M.J. Perez de Vega, M.C. Foces-Foces, F. Hernandez Cano, R.M. Claramunt and J . Elguero, Chemica Scripta, 25 , 230 ( 1 9 8 5 ) . A. Arques, H. Hernandez, P. Molina and M.J. Vilaplana, Synthesis, 910

P. Molina, A. Arques and H.Hernandez, Synthesis, 1 0 2 1 ( 1 9 8 3 ) . P . Molina, M. Alajarin and M.J. Vilaplana, Heterocycles, 2 3 , 6 4 1 ( 1 9 8 5 ) . P. Molina, M. Alajarin and M.J. Perez de Vega, Ann. Chem. (in press). P. Molina, M. Alajarin, J.R. Saez, M.C. Foces-Foces, F. Hernandez Cano, R.M. Claramunt and J. Elguero, J . Chem. SOC. Perkin Trans I, (in press). P . Molina, M. Alajarin and J.R. Saez, Synthesis, 9 8 3 ( 1 9 8 4 ) .

( 1 9 8 1 ) *

- 9 8 5 -