Kärtner, Annerose

Wanner, Klaus Th.

English

Universität München: Elektronischen Publikationen

International 
~ and + 
Hgteroc>db 
lemistry 
V o l u m e 2 6 
N u m b e r 4 
ISSN 0 3 8 5 - 5 4 1 4 
HETEROCYCLES 
A n Internat ional Journa l f o r Reviews and Commun ica t ions 
in Heterocyc l ic Chemis t ry 
C O N T E N T S 
C O M M U N I C A T I O N S 
GHEORGHE SURPATEANU, A L A I N LABLACHE-COMBIER, PIERRE 
G R A N D C L A U D O N , and BERNARD M O U C H E L . Cyc loaddi t ion 
Reaction of 1,2,4-Triazol ium Phenacyl ides w i t h Cinnamic Esters 8 6 3 
ISTVÄN BITTER, GABOR T Ö T H , ISTVÄN HERMECZ, and ZOLTÄN 
MESZÄROS. Nitrogen Bridgehead Compounds Part 5 9 . Nucleophilic 
Subst i tut ion Reactions of 9 - B r o m o - 6 , 7 , 8 , 9 - t e t r a h y d r o - 4 # - p y r i d o -
[1 ,2 -a ]py r im id in -4 -ones 8 6 9 
YASUOKI M U R A K A M I , Y U U S A K U Y O K O Y A M A , CHIYOKO A O K I , 
CHIEMI MIYAGI , T O S H I K O W A T A N A B E , and TAICHI O H M O T O . 
A N e w Route to 4 - 0 x y g e n a t e d /?-Carbolines: The Tota l Synthesis 
of Crenat ine 8 7 5 
HANH DUFAT-TRINH V A N , ELISABETH SEGUIN, FRANQOIS TILLEQUIN, 
and MICHEL K O C H . Tota l Synthesis of 7 - H y d r o x y - " 9 - o x a " - a n t h r a -
cycl inone and Glycoside Derivat ives 8 7 9 
SHIZUAKI MURATA, T A K A S H I S U G I M O T O , and S A D A O M A T S U U R A . 
A Novel Ring Format ion of 1 ,2-Dihydroquinoxal ines 8 8 3 
H A N S LUDESCHER, C H I N G - P O N G M A K , GERHARD SCHULZ, and 
H A N S FLIRI. Chemis t ry of Penicil l in Diazoketones. Part I I : From 
Beta-Iactam to Beta-Iactone . . 8 8 5 
M A S A N O R I S O M E I , F U M I O Y A M A D A , and Y O S H I H I K O M A K I T A . 
Total Syntheses of (± ) -Agroc lav ine - l , (± ) -6 -Nor -chanoc lav ine - l l / 
and (±) -Chanoc lav ine- l l 8 9 5 
MONA HASSAN M O H A M E D , NADIA SOBHY IBRAHIM, and M O H A M E D 
HILMY ELNAGDI . Nitr i les in Heterocyc l ic Synthes is : Synthesis o f 
Some N e w Pyr id ine, Pyridazine and Pyr imid ine Derivat ives — 8 9 9 
EBTISAM ABDEL AZIZ HAFEZ, M O H A M E D H I L M Y E L N A G D I , ABDEL 
G H A N I ALI ELAGAMEY, and FATHY M O H A M E D ABDEL AZIZ 
EL-TAWEEL. Nitr i les in Heterocyc l ic Synthes is : Nove! Synthesis o f 
Benzo[c]coumarin and of Benzo[c]pyrano[3,2-c]quinoline Derivatives 9 0 3 
JUZO NAKAYAMA, MASAHIRO SHIBUYA, and M A S A M A T S U HOSHINO. 
Preparat ion of 2 ,5-Diacy lse lenophenes by Condensat ion of a,a-
Diketo Selenides w i t h Glyoxal 9 0 9 
M A S A K A T S U M A T S U M O T O and N O B U K O W A T A N A B E . A Facile 
Synthesis of 4 -Mercap to indo les 9 1 3 
K L A U S T H . W A N N E R and ANNEROSE KÄRTNER. Isomerizat ion of 
A/-Acyl-1,2,5,6-tetrahydropyridines to /V-Acyl-enamines by Palladium 
on Carbon 9 1 7 
K L A U S T H . W A N N E R and ANNEROSE KÄRTNER. Asymmet r i e a-
Amidoa lky la t ion . Synthesis of ^-Subst i tu ted Piperidines of High 
Enant iomer ic Purity 9 2 1 
J U N K O K O Y A M A , TERUYO O K A T A N I , KIYOSHI T A G A H A R A , YUKIO 
SUZUTA, and HIROSHI IRIE. Synthesis of Guaipyr id ine, Epiguai-
pyr id ine, and Related C o m p o u n d s 9 2 5 
M A K O T O W A D A , HIDEKI A IURA, and KIN-YA AKIBA. Synthesis of 
Pyrrol id ine Der ivat ives by Improved Aminose lenat ion via Add i t i on 
of Boron Tr i f luor ide Complex of D ihomoal ly lcuprate to A ld imines 
Conta in ing a -Hydrogen 9 2 9 
YOSHITERU O S H I M A , M A K l O K A M O T O , and HIROSHI H IK INO. 
Epimedins A, B and C, Flavonoid Glycosides of Epimedium koreanum 
Herbs 9 3 5 
J U Z O N A K A Y A M A , YOICHI N A K A M U R A , SHIGERU M U R A B A Y A S H I , 
and M A S A M A T S U H O S H I N O . Preparat ion of ^-Quinque- and a-
Sept i th iophenes and Thei r Posit ional Isomers 9 3 9 
YANG-CHANG W U , T IAN-SHUNG W U , MASATAKE NIWA, SHENG-TEH 
LU, and YOSHIMASA HIRATA. Thalicsessine, a New C 2 o-Diterpenoid 
Alkalo id f r o m Thalictrum sessile Hayata 9 4 3 
HETEROCYCLIC PAPERS 
L A J O S KOVÄCS, PAL HERCZEGH, GYULA BATTA, and ISTVÄN 
FARKAS. T w o Acyc l ic Analogues of 2-ß-D-Ribofuranosyl th iazole-4-
carboxamide (Tiazofurin) 9 4 7 
GURY Z V I L I C H O V S K Y and M O R D E C H A I DAVID . Molecular St ructure 
and Stabi l i ty of Isoxazolium Enolates 9 6 1 
SHARON MARINUZZI-BROSEMER, BHALCHANDRA H. PATWARDHAN, 
KENNETH A. GREENBERG, and D O N A L D C. D ITTMER. In teract ion 
of Thietes w i t h Elect ron-def ic ient Molecules 9 6 9 
JOSE M. A L O N S O , M. ROSARIO M A R T I N , JAVIER DE M E N D O Z A , 
T O M A S TORRES, and JOSfE ELGUERO. Proton-ionizable Macrocycles 
Conta in ing 1,2,4-Triazole and 4 -Amino-1 ,2 ,4 - t r iazo le Subunits 9 8 9 
C H I N G - P O N G M A K , GERHARD S C H U L Z , and H A N S FLIRI. Chemis t ry 
of Penicil l in Diazoketones. Part I I I : T r a n s f o r m a t i o n of Tr icyc l ic 
Beta-Iactams 1 0 0 1 
ETSUKO K A W A S H I M A , Y U K O A N D O , K A T S U M I TABEI , and HIROSHI 
M I Y A M A E . Cycl ization of C- and O-Acyl Der ivat ives of p-Toluamide 
O-Acetoacety lox ime 1 0 1 5 
PAUL D. W O O D G A T E , J O H N M. HERBERT, and W I L L I A M A. DENNY. 
The Preparation of Pyrido[4,3,2-ofe]quinazoline and Pyrido[3,4,5-c/e]-
quinazoline 1 0 2 9 
J O H N M. HERBERT, PAUL D. W O O D G A T E , and W I L L I A M A. DENNY. 
Format ion of per/'-Fused Heterocyc les by Int ramolecular Displace-
ment of Halide 1 0 3 7 
J O H N M. HERBERT, PAUL D. W O O D G A T E , and W I L L I A M A. DENNY. 
Behaviour of Some Perimidines t o w a r d s Oxidants 1 0 4 3 
REVIEWS 
A H M E D K A M A L and PRALHAD B. SATTUR. Chlorosulfonyl Isocyanate:. 
A Novel Reagent f o r the Synthesis o f Heterocyc les 1 0 5 1 
ARYA K. MUKERJEE. Az lactones: Retrospect and Prospect 1 0 7 7 
N E W HETEROCYCLIC NATURAL PRODUCTS 
Polyacetates 1 0 9 9 
Aromat i cs 1 1 0 2 
Terpenes 1 1 1 1 
Steroids 1 1 2 9 
Alkaloids 1 1 3 0 
Ant ib io t ics 1 1 3 9 
Miscel laneous 1 1 4 4 
T O T A L SYNTHESIS OF HETEROCYCLIC NATUR AL PRODUCTS 
Polyacetates 1 1 4 5 
Aromat ics 1 1 4 8 
Terpenes 1 1 5 0 
Alkaloids 1 1 5 1 
Ant ib iot ics 1 1 5 8 
Miscel laneous 11 5 9 
HETEROCYCLES, Vol. 26, No. 4, 1987 
ISOMERIZATION OF N-ACYL-1,2,5,6-TETRAHYDROPYRIDINES TO N-ACYL-ENAMINES BY 
PALLADIUM ON CARBON 
Klaus Th. Wanner and Annerose Kärtner 
I n s t i t u t für Pharmazie und LebensmittelChemie der Universität München, 
Sophienstrasse 10, 8000 München 2, FRG 
A b s t r a c t - A l l y l i c amides J_ were rearranged t o enamides 2 using p a l l a d i u m 
on carbon as c a t a l y s t . 
Carbon-carbon bond formation at the a~ and ß-positions of amines i s of c o n s i d e r a b l e i n t e r e s t i n 
p r e p a r a t i v e o r g a n i c chemistryj i t can be achieved (e.g. by) u t i l i z i n g enamides [ e . g . 2 ) as s t a r -
t i n g Compounds 1. As some of the most important s y n t h e t i c pathways t o t h i s c l a s s of Compounds may 
be mentioned the a c y l a t i o n of imines with a c i d C h l o r i d e s or anhydrides ^ and the e l i m i n a t i o n 
2 3 of methanol from a - m e t h o x y l a t e d amides , which are r e a d i l y a v a i l a b l e by e l e c t r o c h e m i c a l methods . 
In the course of our s t u d i e s concerning the asymmetric a - a m i d o a l k y l a t i o n mediated by c h i r a l en-
amides, we looked f o r a simple and e f f i c i e n t route t o c y c l i c enamides of type 2 . In t h i s case 
the imine a c y l a t i o n sequence was not f e a s i b l e , s i n c e the corresponding imine does not e x i s t 5 , 
and the e l e c t r o c h e m i c a l o x i d a t i o n d i d not appear promising s i n c e a high degree of S u b s t i t u t i o n 
i n the a c y l moiety i s known t o reduce the y i e l d 6 . We t h e r e f o r e envisaged the s y n t h e s i s of enamides 
2 from 2 bY double bond i s o m e r i z a t i o n as an a t t r a c t i v e a l t e r n a t i v e . S i m i l a r i s o m e r i z a t i o n s e f f e c t e d 
by i r o n , rhodium and ruthenium c a t a l y s t s , have been r e p o r t e d 7 . 
A f t e r s e v e r a l experiments employing v a r i o u s rhodium complexes we found t h a t the i s o m e r i z a t i o n 
of J_a t o enamide 2a i s best e f f e c t e d by palladium on carbon i n THF-NEt^ a t 120°C. The conversion 
(1a-2a) was almost complete w i t h i n 3 h (>90% by NMR) and a f t e r 6 h (conversion >95%) we i s o l a t e d 
2a i n 80.5% y i e l d . T his r e a c t i o n appears to represent a g e n e r a l method f o r the s y n t h e s i s of en-
amides of type 2 . The r e s u l t s are shown i n the T a b l e . C r u c i a l to t h i s process, when employed f o r 
the s y n t h e s i s of hydroxy s u b s t i t u t e d enamides i s the presence of NEt . Without t h i s a d d i t i v e 
the rearrangement ( t o a f f o r d e.g. 2a) was fol l o w e d by an i n t r a m o l e c u l a r r i n g c l o s u r e (entry 2 ) . 
I t i s worthwhile t o note t h a t i n the i s o m e r i z a t i o n e x c e l l e n t r e s u l t s were obtained even with 
1/50(w/w) of c a t a l y s t (entry 3). 
In a t y p i c a l procedure, a mixture of 217.3 mg (1.0 mmol) J a , 10.9 mg Pd-C(10% Pd) and 1 ml THF/NEt 
(8/2) was heated 6 h at 120°C i n a s e a l e d tube. A f t e r f i l t r a t i o n the or g a n i c l a y e r was evaporated 
under reduced pressure and the r e s i d u e was p u r i f i e d by r a d i a l chromatography (SiO^, n-hex/EtOAc) 
to g i v e 2a (174.9 mg, 80.5%). 
Table 
e n t r y substr.** R N E t ^ c o n d i t i o n s a prod. y i e l d ( % ) k [ g ] ^ c 
a) Pd-C (10% Pd)/ s u b s t r . (w/w), temp., r e a c t i o n time. b) Y i e l d of pure products from r a d i a l 
chromatography. A l l Compounds were f u l l y c h a r a c t e r i z e d by 1H-NMR, IR and MS s p e c t r a and by C,H,N 
combustion analyses. c) C a l c u l a t e d from [ a ] c . _ and [a] __ Q, c-1.0, CH.OH. d) R a t i o 2a/3/4 
54b D / O ~> 
determined by HPLC. e) 3: ^ ;4: H 
0. Ci?-
ph 
ACKNOWLEDGEMENT 
We would l i k e t o thank P r o f . Dr. F. Eiden f o r generous support. 
- 9 1 8 -
HETEROCYCLES, Vol. 26, No. 4, 1987 
REFERENCES AND NOTES 
(1) For reviews, see: a) H.E. Zaugg, S y n t h e s i s , 1984, 85; H.E. Zaugg, i b i d . , 1984, 181; b) 
G. R. Lenz, ibid.,1978, 489. See a l s o : c) T. Shono, Y. Matsumura, K, Tsubata,and 
Y. Sugihara, Tetrahedron L e t t . , 2 3 , 1201 (1982). 
(2) K. Nyberg, S y n t h e s i s , 1976, 545. 
(3) T. Shono: E l e c t r o o r g a n i c chemistry as new t o o l i n organic s y n t h e s i s . S p r i n g e r - V e r l a g , 
B e r l i n 1984, p. 63. 
(4) See the accompanying paper. 
(5) K. Warning and M. M i t z l a f f , Tetrahedron L e t t . , 1979, 1565. 
(6) M. M i t z l a f f , K. Warning, and H. Jensen, L i e b i g s Ann. Chem.,1978, 1713. 
(7) J.K. S t i l l e and Y. Becker, J . Org. Chem.,45, 2139(1980). 
(8) The s t a r t i n g Compounds were prepared as f o l l o w s : Ja.: treatment of 2,2-dimethyl-5-phenyl-
1,3-dioxolan-4-one with 1,2,5,6-tetrahydropyridine (2 eq.) i n THF(25°C, 4 5 h, 82.8%); Jb: 
r e a c t i o n of (-)-camphanic a c i d C h l o r i d e and 1,2,5,6-tetrahydropyridine; Je: r e d u e t i o n of 
Jb with 1.5 eq. NaBH^ i n diglyme (120°C, 60 h, 64.6%); J d : m e t h y l a t i o n of Je (1.1 eq. KH, 
THF, 0°C; 2.0 eq. CH 3I -60°C-*-20°C, 60.4%). 
Received, 22nd December, 1986 
— 919 — 


Isomerization of N-acyl-1,2,5,6-tetrahydropyridines to N-acyl-enamines by palladium on carbon

Open Access LMU ( Ludwig-Maximilians-Univ. München)

International ~ and + Hgteroc>db lemistry V o l u m e 2 6 N u m b e r 4 ISSN 0 3 8 5 - 5 4 1 4 HETEROCYCLES A n Internat ional Journa l f o r Reviews and Commun ica t ions in Heterocyc l ic Chemis t ry C O N T E N T S C O M M U N I C A T I O N S GHEORGHE SURPATEANU, A L A I N LABLACHE-COMBIER, PIERRE G R A N D C L A U D O N , and BERNARD M O U C H E L . Cyc loaddi t ion Reaction of 1,2,4-Triazol ium Phenacyl ides w i t h Cinnamic Esters 8 6 3 ISTVÄN BITTER, GABOR T Ö T H , ISTVÄN HERMECZ, and ZOLTÄN MESZÄROS. Nitrogen Bridgehead Compounds Part 5 9 . Nucleophilic Subst i tut ion Reactions of 9 - B r o m o - 6 , 7 , 8 , 9 - t e t r a h y d r o - 4 # - p y r i d o -[1 ,2 -a ]py r im id in -4 -ones 8 6 9 YASUOKI M U R A K A M I , Y U U S A K U Y O K O Y A M A , CHIYOKO A O K I , CHIEMI MIYAGI , T O S H I K O W A T A N A B E , and TAICHI O H M O T O . A N e w Route to 4 - 0 x y g e n a t e d /?-Carbolines: The Tota l Synthesis of Crenat ine 8 7 5 HANH DUFAT-TRINH V A N , ELISABETH SEGUIN, FRANQOIS TILLEQUIN, and MICHEL K O C H . Tota l Synthesis of 7 - H y d r o x y - " 9 - o x a " - a n t h r a -cycl inone and Glycoside Derivat ives 8 7 9 SHIZUAKI MURATA, T A K A S H I S U G I M O T O , and S A D A O M A T S U U R A . A Novel Ring Format ion of 1 ,2-Dihydroquinoxal ines 8 8 3 H A N S LUDESCHER, C H I N G - P O N G M A K , GERHARD SCHULZ, and H A N S FLIRI. Chemis t ry of Penicil l in Diazoketones. Part I I : From Beta-Iactam to Beta-Iactone . . 8 8 5 M A S A N O R I S O M E I , F U M I O Y A M A D A , and Y O S H I H I K O M A K I T A . Total Syntheses of (± ) -Agroc lav ine - l , (± ) -6 -Nor -chanoc lav ine - l l / and (±) -Chanoc lav ine- l l 8 9 5 MONA HASSAN M O H A M E D , NADIA SOBHY IBRAHIM, and M O H A M E D HILMY ELNAGDI . Nitr i les in Heterocyc l ic Synthes is : Synthesis o f Some N e w Pyr id ine, Pyridazine and Pyr imid ine Derivat ives — 8 9 9 EBTISAM ABDEL AZIZ HAFEZ, M O H A M E D H I L M Y E L N A G D I , ABDEL G H A N I ALI ELAGAMEY, and FATHY M O H A M E D ABDEL AZIZ EL-TAWEEL. Nitr i les in Heterocyc l ic Synthes is : Nove! Synthesis o f Benzo[c]coumarin and of Benzo[c]pyrano[3,2-c]quinoline Derivatives 9 0 3 JUZO NAKAYAMA, MASAHIRO SHIBUYA, and M A S A M A T S U HOSHINO. Preparat ion of 2 ,5-Diacy lse lenophenes by Condensat ion of a,a-Diketo Selenides w i t h Glyoxal 9 0 9 M A S A K A T S U M A T S U M O T O and N O B U K O W A T A N A B E . A Facile Synthesis of 4 -Mercap to indo les 9 1 3 K L A U S T H . W A N N E R and ANNEROSE KÄRTNER. Isomerizat ion of A/-Acyl-1,2,5,6-tetrahydropyridines to /V-Acyl-enamines by Palladium on Carbon 9 1 7 K L A U S T H . W A N N E R and ANNEROSE KÄRTNER. Asymmet r i e a-Amidoa lky la t ion . Synthesis of ^-Subst i tu ted Piperidines of High Enant iomer ic Purity 9 2 1 J U N K O K O Y A M A , TERUYO O K A T A N I , KIYOSHI T A G A H A R A , YUKIO SUZUTA, and HIROSHI IRIE. Synthesis of Guaipyr id ine, Epiguai-pyr id ine, and Related C o m p o u n d s 9 2 5 M A K O T O W A D A , HIDEKI A IURA, and KIN-YA AKIBA. Synthesis of Pyrrol id ine Der ivat ives by Improved Aminose lenat ion via Add i t i on of Boron Tr i f luor ide Complex of D ihomoal ly lcuprate to A ld imines Conta in ing a -Hydrogen 9 2 9 YOSHITERU O S H I M A , M A K l O K A M O T O , and HIROSHI H IK INO. Epimedins A, B and C, Flavonoid Glycosides of Epimedium koreanum Herbs 9 3 5 J U Z O N A K A Y A M A , YOICHI N A K A M U R A , SHIGERU M U R A B A Y A S H I , and M A S A M A T S U H O S H I N O . Preparat ion of ^-Quinque- and a-Sept i th iophenes and Thei r Posit ional Isomers 9 3 9 YANG-CHANG W U , T IAN-SHUNG W U , MASATAKE NIWA, SHENG-TEH LU, and YOSHIMASA HIRATA. Thalicsessine, a New C 2 o-Diterpenoid Alkalo id f r o m Thalictrum sessile Hayata 9 4 3 HETEROCYCLIC PAPERS L A J O S KOVÄCS, PAL HERCZEGH, GYULA BATTA, and ISTVÄN FARKAS. T w o Acyc l ic Analogues of 2-ß-D-Ribofuranosyl th iazole-4-carboxamide (Tiazofurin) 9 4 7 GURY Z V I L I C H O V S K Y and M O R D E C H A I DAVID . Molecular St ructure and Stabi l i ty of Isoxazolium Enolates 9 6 1 SHARON MARINUZZI-BROSEMER, BHALCHANDRA H. PATWARDHAN, KENNETH A. GREENBERG, and D O N A L D C. D ITTMER. In teract ion of Thietes w i t h Elect ron-def ic ient Molecules 9 6 9 JOSE M. A L O N S O , M. ROSARIO M A R T I N , JAVIER DE M E N D O Z A , T O M A S TORRES, and JOSfE ELGUERO. Proton-ionizable Macrocycles Conta in ing 1,2,4-Triazole and 4 -Amino-1 ,2 ,4 - t r iazo le Subunits 9 8 9 C H I N G - P O N G M A K , GERHARD S C H U L Z , and H A N S FLIRI. Chemis t ry of Penicil l in Diazoketones. Part I I I : T r a n s f o r m a t i o n of Tr icyc l ic Beta-Iactams 1 0 0 1 ETSUKO K A W A S H I M A , Y U K O A N D O , K A T S U M I TABEI , and HIROSHI M I Y A M A E . Cycl ization of C- and O-Acyl Der ivat ives of p-Toluamide O-Acetoacety lox ime 1 0 1 5 PAUL D. W O O D G A T E , J O H N M. HERBERT, and W I L L I A M A. DENNY. The Preparation of Pyrido[4,3,2-ofe]quinazoline and Pyrido[3,4,5-c/e]-quinazoline 1 0 2 9 J O H N M. HERBERT, PAUL D. W O O D G A T E , and W I L L I A M A. DENNY. Format ion of per/'-Fused Heterocyc les by Int ramolecular Displace-ment of Halide 1 0 3 7 J O H N M. HERBERT, PAUL D. W O O D G A T E , and W I L L I A M A. DENNY. Behaviour of Some Perimidines t o w a r d s Oxidants 1 0 4 3 REVIEWS A H M E D K A M A L and PRALHAD B. SATTUR. Chlorosulfonyl Isocyanate:. A Novel Reagent f o r the Synthesis o f Heterocyc les 1 0 5 1 ARYA K. MUKERJEE. Az lactones: Retrospect and Prospect 1 0 7 7 N E W HETEROCYCLIC NATURAL PRODUCTS Polyacetates 1 0 9 9 Aromat i cs 1 1 0 2 Terpenes 1 1 1 1 Steroids 1 1 2 9 Alkaloids 1 1 3 0 Ant ib io t ics 1 1 3 9 Miscel laneous 1 1 4 4 T O T A L SYNTHESIS OF HETEROCYCLIC NATUR AL PRODUCTS Polyacetates 1 1 4 5 Aromat ics 1 1 4 8 Terpenes 1 1 5 0 Alkaloids 1 1 5 1 Ant ib iot ics 1 1 5 8 Miscel laneous 11 5 9 HETEROCYCLES, Vol. 26, No. 4, 1987 ISOMERIZATION OF N-ACYL-1,2,5,6-TETRAHYDROPYRIDINES TO N-ACYL-ENAMINES BY PALLADIUM ON CARBON Klaus Th. Wanner and Annerose Kärtner I n s t i t u t für Pharmazie und LebensmittelChemie der Universität München, Sophienstrasse 10, 8000 München 2, FRG A b s t r a c t - A l l y l i c amides J_ were rearranged t o enamides 2 using p a l l a d i u m on carbon as c a t a l y s t . Carbon-carbon bond formation at the a~ and ß-positions of amines i s of c o n s i d e r a b l e i n t e r e s t i n p r e p a r a t i v e o r g a n i c chemistryj i t can be achieved (e.g. by) u t i l i z i n g enamides [ e . g . 2 ) as s t a r -t i n g Compounds 1. As some of the most important s y n t h e t i c pathways t o t h i s c l a s s of Compounds may be mentioned the a c y l a t i o n of imines with a c i d C h l o r i d e s or anhydrides ^ and the e l i m i n a t i o n 2 3 of methanol from a - m e t h o x y l a t e d amides , which are r e a d i l y a v a i l a b l e by e l e c t r o c h e m i c a l methods . In the course of our s t u d i e s concerning the asymmetric a - a m i d o a l k y l a t i o n mediated by c h i r a l en-amides, we looked f o r a simple and e f f i c i e n t route t o c y c l i c enamides of type 2 . In t h i s case the imine a c y l a t i o n sequence was not f e a s i b l e , s i n c e the corresponding imine does not e x i s t 5 , and the e l e c t r o c h e m i c a l o x i d a t i o n d i d not appear promising s i n c e a high degree of S u b s t i t u t i o n i n the a c y l moiety i s known t o reduce the y i e l d 6 . We t h e r e f o r e envisaged the s y n t h e s i s of enamides 2 from 2 bY double bond i s o m e r i z a t i o n as an a t t r a c t i v e a l t e r n a t i v e . S i m i l a r i s o m e r i z a t i o n s e f f e c t e d by i r o n , rhodium and ruthenium c a t a l y s t s , have been r e p o r t e d 7 . A f t e r s e v e r a l experiments employing v a r i o u s rhodium complexes we found t h a t the i s o m e r i z a t i o n of J_a t o enamide 2a i s best e f f e c t e d by palladium on carbon i n THF-NEt^ a t 120°C. The conversion (1a-2a) was almost complete w i t h i n 3 h (>90% by NMR) and a f t e r 6 h (conversion >95%) we i s o l a t e d 2a i n 80.5% y i e l d . T his r e a c t i o n appears to represent a g e n e r a l method f o r the s y n t h e s i s of en-amides of type 2 . The r e s u l t s are shown i n the T a b l e . C r u c i a l to t h i s process, when employed f o r the s y n t h e s i s of hydroxy s u b s t i t u t e d enamides i s the presence of NEt . Without t h i s a d d i t i v e the rearrangement ( t o a f f o r d e.g. 2a) was fol l o w e d by an i n t r a m o l e c u l a r r i n g c l o s u r e (entry 2 ) . I t i s worthwhile t o note t h a t i n the i s o m e r i z a t i o n e x c e l l e n t r e s u l t s were obtained even with 1/50(w/w) of c a t a l y s t (entry 3). In a t y p i c a l procedure, a mixture of 217.3 mg (1.0 mmol) J a , 10.9 mg Pd-C(10% Pd) and 1 ml THF/NEt (8/2) was heated 6 h at 120°C i n a s e a l e d tube. A f t e r f i l t r a t i o n the or g a n i c l a y e r was evaporated under reduced pressure and the r e s i d u e was p u r i f i e d by r a d i a l chromatography (SiO^, n-hex/EtOAc) to g i v e 2a (174.9 mg, 80.5%). Table e n t r y substr.** R N E t ^ c o n d i t i o n s a prod. y i e l d ( % ) k [ g ] ^ c a) Pd-C (10% Pd)/ s u b s t r . (w/w), temp., r e a c t i o n time. b) Y i e l d of pure products from r a d i a l chromatography. A l l Compounds were f u l l y c h a r a c t e r i z e d by 1H-NMR, IR and MS s p e c t r a and by C,H,N combustion analyses. c) C a l c u l a t e d from [ a ] c . _ and [a] __ Q, c-1.0, CH.OH. d) R a t i o 2a/3/4 54b D / O ~> determined by HPLC. e) 3: ^ ;4: H 0. Ci?-ph ACKNOWLEDGEMENT We would l i k e t o thank P r o f . Dr. F. Eiden f o r generous support. - 9 1 8 -HETEROCYCLES, Vol. 26, No. 4, 1987 REFERENCES AND NOTES (1) For reviews, see: a) H.E. Zaugg, S y n t h e s i s , 1984, 85; H.E. Zaugg, i b i d . , 1984, 181; b) G. R. Lenz, ibid.,1978, 489. See a l s o : c) T. Shono, Y. Matsumura, K, Tsubata,and Y. Sugihara, Tetrahedron L e t t . , 2 3 , 1201 (1982). (2) K. Nyberg, S y n t h e s i s , 1976, 545. (3) T. Shono: E l e c t r o o r g a n i c chemistry as new t o o l i n organic s y n t h e s i s . S p r i n g e r - V e r l a g , B e r l i n 1984, p. 63. (4) See the accompanying paper. (5) K. Warning and M. M i t z l a f f , Tetrahedron L e t t . , 1979, 1565. (6) M. M i t z l a f f , K. Warning, and H. Jensen, L i e b i g s Ann. Chem.,1978, 1713. (7) J.K. S t i l l e and Y. Becker, J . Org. Chem.,45, 2139(1980). (8) The s t a r t i n g Compounds were prepared as f o l l o w s : Ja.: treatment of 2,2-dimethyl-5-phenyl-1,3-dioxolan-4-one with 1,2,5,6-tetrahydropyridine (2 eq.) i n THF(25°C, 4 5 h, 82.8%); Jb: r e a c t i o n of (-)-camphanic a c i d C h l o r i d e and 1,2,5,6-tetrahydropyridine; Je: r e d u e t i o n of Jb with 1.5 eq. NaBH^ i n diglyme (120°C, 60 h, 64.6%); J d : m e t h y l a t i o n of Je (1.1 eq. KH, THF, 0°C; 2.0 eq. CH 3I -60°C-*-20°C, 60.4%). Received, 22nd December, 1986 — 919 — 

Isomerization of N-acyl-1,2,5,6-tetrahydropyridines to N-acyl-enamines by palladium on carbon

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