J. CHEM. SOC., CHEM. COMMUN.,
1994
2629
Palladium-catalysed Regioselective Cyclisation
of
Unsaturated
Bromoanilinoalkenenitriles
Chau-Chen Yang,* a Pei-Jiun Sun a and Jim-Min Fang b
a Department of Cosmetic Science, Chia Nan Junior College of Pharmacy, Tainan 777, Taiwan, Republic of China
b Department of Chemistry, National Taiwan University, Taipei 107, Taiwan, Republic of China
a-(u-Bromoani1ino)alkenenitriles are converted t o 2-( methylamino)benzonitrile and varied y-carbolines by catalysis with palladium; the reactions may involve intramolecular aryl additions to the cyano group and other processessuch as cyano group transposition, electrocyclisation, ethyl group transfer and oxidative aromatisation.
Heck reactions are important palladium-catalysed reactions for carbon-carbon bond formation such as the well documen- ted arylation of olefins;' the corresponding arylation of a cyano group is, however, not reported. Our investigation of the palladium-catalysed cyclisations of varied a-(o-bromoani- 1ino)alkenenitriles 1 and 2 showed that the reactions occurred
exclusively at the cyano group to give 2-(methy1amino)benzo- nitrile2 3 and y-carbolines3 4 and 5 (Scheme 1). Non-conju- gated alkenenitriles la-c were prepared,4 by condensation of
equimolar amounts of an appropriate unsaturated aldehyde, potassium cyanide, N-methyl-o-bromoanilines and hydro- chloric acid (12 mol dm-3). By a similar procedure, Id was
prepared in 78% yield from cyclopropanecarbaldehyde. Treatment of la-c with the strong base ButOK in ButOH-
THF at 0 "C gave the more stable conjugated a-amino alkenenitriles 2a-c having the 2E-configuration.6 In a typical
Me l b 3
I i
l i e 4 Me 2b Me 5bScheme 1 Reugents and conditions: i , ButOK (1 equiv.), Bu'OH-THF,
0 "C, 1 h ; i i . Pd(OAc)?, Ph3P. Et3N, DMF, 100 "C, 6 h
procedure, l b (1 mmol) in DMF (15 ml) was treated with Pd(OAc);? (0.1 mmol), Ph3P (0.2 mmol) and Et3N (1.2 mmol)
for 6 h at 100 "C under an argon atmosphere.7 The reaction mixture was cooled and EtOAc (30 ml) was added. The mixture was washed with water, the organic phase was concentrated and chromatographed on a silica-gel column by elution with gradients of EtOAc-hexane to give 2-(methylam- ino)benzonitrile 3 and y-carboline 4 in 38 and 36% yields, respectively. Benzonitrile 3 was also obtained in 72-85% yields from the reactions of l a , l c and Id. The palladium-
catalysed reactions of 2a-c afforded y-carbolines 5a-c in
7548% yields. The structures of 4 and 5 were rigorously determined.
t
The mechanisms for the present palladium-catalysed reac- tions are not fully understood. The reactions of l a 4 are
presumably initiated by oxidative insertion of Pd(J to the bromophenyl groups (Scheme 2). The organopalladium 6 undergoes cyclisation by attacking at the cyano group, giving
7, but not at the olefinic double bonds. The iminoindoline 7 may rupture to an iminium ion 8, which is subsequently
hydrolysed to give 2-(methylamino)benzonitrile and aldehy- des RCHO. When R is a styryl group, 7 may react further with cinnamaldehyde to give y-carboline 4. Compounds 2a-c also
undergo oxidative insertions with PdO, giving the interme- diates 9. For 2c (R is a butenyl group), a 6n electrocyclisation and subsequent elimination of hydridopalladium produce y-carboline 5c. Though the intermediate 9 derived from 2a,b
(R = Et or PhCH2) cannot undergo electrocyclisation, it may take an ethyl group from Et,NH+, giving 10. Subsequent
elimination of hydridopalladium, electrocyclisation and oxi- dative aromatisation would furnish the y-carbolines 5a,b
(Scheme 3). Pd" (OAcb PdL,Br l a ; R = MeCH=CH b; R = PhCH=CH c; R = MeCH=CHCH=CH d; R = (CH2)2CH Me electrocyclisation for Pc, R = EtCH=CH Me 10 R'=MewPh or Et,N
a--yEt
"\
a7-Th
R' PdL2Br I N I Me t4e electrocydisation and oxidative aromatisationI
R=PhCH=CH,0-c"
+ PhCH=CHCHO \'
Ph N I Me 4O--DEt
I Me 5cQ-ah
R' I Me 5a R'= Me bR'=Ph Scheme 2 Scheme 3J. CHEM. SOC., CHEM. COMMUN.,
1994
Our study of the palladium-catalysed reactions shows three uncommon features: (i) transposition of the cyano group in conversion of l a 4 to 3,
(ii)
two covalent bonds are formed incoversion of 2c to 5c by consecutive aryl-cyano addition and electrocyclisation, and (iii) involvement of an ethyl group transfer in conversion of 2a,b to 5a,b.
We thank the National Science Council of the Republic of China for financial support (Grant NSC82-0208-M041-006).
Received, 1st September 1994; Corn. 4105346J
Footnote
-1 All new compounds gave satisfactory spectral and analytical data.
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