Palladium-catalyzed chemoselective intramolecular cyclization of bromoanilinoalkenenitriles

摘要

J. Chem. Soc. Perkin Trans. 1 1997 2843 Palladium-catalyzed chemoselective intramolecular cyclization of bromoanilinoalkenenitriles Chau-Chen Yang,* Huo-Mu Tai and Pei-Jiun Sun Department of Cosmetic Science Chia Nan College of Pharmacy and Science Tainan 717 Taiwan Republic of China middot;-(o-Bromoanilino)alkenenitriles 1andash;f and 2andash;e and middot;-(N-alkenylamino)-lsquor;-(o-bromophenyl)- propanenitriles 7andash;c and 8andash;c undergo palladium-catalyzed conversion into o-(methylamino)benzonitrile 12 o-(alkenylamino)ethenylbenzonitriles 24andash;c N-alkenylanilines 26b 26c 3-benzazepines 29a 29c 31a and 32a ldquor;-carbolines 36 and pyrrolo3,2-bindole 45. The reactions involve intramolecular additions of arylpalladium to the cyano group and subsequent processes such as cyano group transposition hydrolysis electrocyclization ethyl group transfer and oxidative aromatization.A general mechanism for the palladium-catalyzed arylation of a cyano group is proposed. Introduction Heck reactions are important palladium-catalyzed reactions for carbonndash;carbon bond formation such as the well documented arylation of olefins;1 the corresponding arylation of a cyano group is however unprecedented except for a previous report from our group.2 A series of N-methyl-(o-bromoanilino)alk-3- enenitriles 1andash;e 2-anilino-2-cyclopropylacetonitrile 1f Nmethyl-( o-bromoanilino)alk-2-enenitriles 2andash;e and Nalkenylamino- 3-(o-bromophenyl)propanenitriles 7andash;c 8andash;c have been prepared and their intramolecular palladiumcatalyzed cyclizations studied.2 Most of these compounds have olefin and cyano groups oriented in similar proximity to the arylpalladium complex.The palladium-catalyzed cyclization may occur by two competitive pathways namely by attack on the olefinic function or on the cyano group. This study indicates that the palladium-catalyzed arylation occurs in most cases selectively at the cyano group to afford o-(methylamino)- benzonitrile 12 o-(alkenylamino)ethenylbenzonitriles 24 Nalkenylanilines 26 g-carbolines 36 and pyrrolo3,2-bindole 45. Results and discussion Non-conjugated a-(o-bromoanilino)alkenenitriles 1andash;e were prepared eqn. (1) by condensation of equimolar amounts of an appropriate unsaturated aldehyde potassium cyanide and N-methyl-o-bromoaniline 3 in the presence of hydrochloric acid (12 M).4 a-Amino(cyclopropyl)acetonitrile 1f was similarly prepared from cyclopropanecarbaldehyde.Treatment of 1andash;e with a strong base But-OK in ButOHndash;THF at 0 8C for 2 h gave the thermodynamically favoured conjugated a-aminoalkenenitriles 2andash;e predominantly as the 2E-isomer (E:Z 10).5 2-(Alkenylamino) acetonitriles 5andash;c 6andash;c prepared from N-alkylations of a-aminonitriles 3 and 4,6 were treated with lithium diisopropylamide (LDA) and o-bromobenzyl bromide to give 2-(alkenylamino)-3-(o-bromophenyl)propanenitriles 7andash;c and 8andash;c eqn. (2).7 In a typical procedure 8 (Table 1) a-(o-bromoanilino) alkenenitrile 1d (1 mmol) in DMF (15 ml) was treated with Pd(OAc)2 (0.1 mmol) PPh3 (0.2 mmol) and Et3N (1.2 mmol) for 6 h at 100 8C under an argon atmosphere to give 2- (methylamino)benzonitrile 12 and g-carboline 17 in 38 and 36 yields respectively. The reactions of 1andash;c e f gave the benzonitrile 12 (60ndash;85) and aldehydes RCHO.A possible mechanism for the palladium-catalyzed reactions 9 is illustrated by the formation of the benzonitrile 12 (Scheme 1). The reactions were presumably initiated by oxidative insertion of Pd0 into the bromophenyl groups. The organopalladium 9 undergoing cyclisation by attack on the cyano group giving 10 but not the olefinic double bonds. The iminoindoline 10 might CN Cl CN CN NMe R R1 NMe CN NH R Br R1 R2 CN N R1 R2 R Br Br NHMe Br Br Br R H O N CN Br R R1 R2 + RNH2 7a R = Ph R1 = R2 = H 7b R = Ph R2 = R2 = Me 7c R = R1 = Ph R2 = H 8a R= Bn R1 = R2 = H 8b R = Bn R1 = R2 = Me 8c R = Bn R1 = Ph R2 = H 5a R = Ph R1 = R2 = H 5b R = Ph R1 = R2 = Me 5c R = R1 = Ph R2= H 6a R= Bn R1 = R2 = H 6b R = Bn R1 = R2 = Me 6c R = Bn R1 = Ph R2 = H 3 R = Ph 4 R = Bn 2 CH2Cl2 40 oC Et3N/CH2Cl2 40 oC Et3N (2) 2a R1 = Et 2b R1 = Bu 2c R1 = Pri 2d R1 = Bn 2e R1 = EtCH=CH 1a R = MeCH=CH 1b R = PrCH=CH 1c R = Me2C=CH 1d R = PhCH=CH 1e R = MeCH=CHCH=CH 1f R = (CH2)2CH ButOH/THF 0 oC 2 h ButOK KCN(aq.) 12 N HCl + (1) 1 LDA/THF 2844 J.Chem. Soc. Perkin Trans. 1 1997 Scheme 1 N Me R CN PdBr N NPdBr Me CN N R Me CN NHMe N N Me N+ Ph Ph PdBr N+ PdBr N Br N CN R Me R N Ph Ph Me PdBr Ph Ph H N Me Ph NH PdBr Ph N Me Ph N Me H H 1a-f PdII(OAc)2 PPh3/DMF Pd0L2 (L = PPh3) + R = PhCH=CH + PhCH=CHCHO + RCHO 12 13 9 10 11 Et3N For 10d 14 17 Brndash; H2O H-shift electrocyclization H-shift Et3N ndash;Pd0 ndash;HBr 15 16 Table 1 Palladium-catalyzed chemoselective intramolecular cyclization of bromoanilinoalkenenitriles a Reaction Products (yield ) b Entry 123456789 10 11 12 13 14 15 16 17 18 19 20 Substrate 1a 1b 1c 1d 1e 1f 7a 7b 7c 8a 8b 8c 2a 2b 2c 2d 2e 2a 2b 2c Base Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Na2CO3 Na2CO3 Na2CO3 time (h) 66666688888866666 12 12 12 Addition to CN 12 (81) 12 (60) 12 (85) 12 (38) 1 17 (36) 12 (72) 12 (80) mdash; 26b (76) 26c (66) 24a (9) 24b (78) 24c (72) 36a (88) 36b (73) 36c (85) 36d (63) 36e (75) 45 (52) 36e (51) 48 (73) Addition to C C mdash;mdash;mdash;mdash;mdash;mdash; 29a (60) 1 31a (18) mdash; 29c (16) 32a (77) mdash;mdash;mdash;mdash;mdash;mdash;mdash;mdash;mdash;mdash; a The reactions were run under an argon atmosphere with 1 equiv.of bromoanilinoalkenenitrile 1.2 equiv of base 20 mol of PH3P and 10 mol of Pd(OAc)2 in DMF at 100 8C. b Isolated yields after purification. yield an iminium ion 11 which is subsequently hydrolyzed to give 2-(methylamino)benzonitrile 12 and aldehydes RCHO.When R is a styryl group the palladium amide 10d reacted further with cinnamaldehyde to give g-carboline 17.10 This process might involve electrocyclization H-shift and elimination of palladium and HBr. Under similar reaction conditions the palladium-catalyzed reactions of 2-(alkenylamino)-3-(o-bromophenyl)propanenitrile 7b afforded the alkenylamine 26b (76). This result was explained in terms of the organopalladium compound (18 and 19) attacking the cyano group selectively (Scheme 2). Thus the benzonitrile iminium salts (22 and 23) generated from the J. Chem. Soc. Perkin Trans. 1 1997 2845 Scheme 2 N R CN R1 PdBr N R R1 CN R1 N R N R1 CN PdBr R R2 NPdBr N R1 R R2 N CN R R1 R2 N R1 CN R R2 CHO CN HN R1 R2 R ndash;Pd0 ndash;HBr ndash;H+ ndash;Brndash; Et3Nndash;DMF 100 oC Pd(OAc)2ndash;PPh3 + 25 for 18b c and19a-c for 18a c and 19a ndash;HCN 29a R = Ph R1 = H 29c R = R1 = Ph 30a R= Bn R1 = H 31a R = Ph R1 = H 32a R = Bn R1 = H 26b R = Ph R1 = R2 = Me 26c R = R1 =Ph R2 = H 24a R = Bn R1 = R2 = H 24b R = Bn R1 = R2 = Me 24c R = Bn R1 = Ph R2 = H 22 R = Ph 23 R = Bn 20 R = Ph 21 R = Bn 27a R = Ph R1 = H 27c R = R1 = Ph 28a R = Bn R1 = H 18a R = Ph R1 = R2 = H 18b R = Ph R1 = R2 = Me 18c R = R1 = Ph R2 = H 19a R = Bn R1 = R2 =H 19b R = Bn R1 = R2 = Me 19c R = Bn R1 = Ph R2 = H H2O ndash;Pd0 Et3N (ndash;Pd0 ndash;HBr) + 7a-c 8a-c R2 = H iminoindoline intermediates (20 and 21) upon elimination of HBr would give the aminovinylbenzonitriles 24 or undergo hydrolysis to give the alkenylamines 26b c.On the other hand analogous organopalladium compounds (18a c) might attack the less hindered double bonds as shown in the transformation of 7a and 7c to 3-benzazepine derivatives 29a (60) and 29c (16).The reactions of 8andash;c followed similar pathways the organopalladium intermediate attacking either the cyano group or the olefinic double bond depending on the nature of the substrates. At elevated reaction temperatures elimination of HCN from 29a and 30a occurred to give the benzazepines 31a and 32a. The palladium-catalyzed reactions of the conjugated bromoanilinoalkenenitriles 2andash;e (as E/Z-mixtures) afforded gcarbolines 36andash;e (63ndash;88 entries 13ndash;17). The organopalladium compound 34e (R1 = butenyl) had the potential to undergo 6p electrocyclization and subsequent elimination of palladium and HBr to produce the g-carboline 36e (Scheme 3). Although the intermediates 34a b d derived from 2a b d (R = Et Bu Bn) could not undergo electrocyclization capture of an ethyl group from Et3NH1 would give 38a b d.Subsequent elimination of palladium and HBr followed by electrocyclization and oxidative aromatization would furnish the g-carbolines 36a b d. The intermediate 34c derived from 2c (R = Pri) underwent electrocyclization in a different way via 40 to furnish the 4-isopropyl-gcarboline 36c. In order to determine whether the ethyl group was transferred from Et3N in the conversion of 2andash;c into g-carbolines 36andash;c we replaced Et3N with Na2CO3 (1.2 equiv.) as the base in the palladium-catalyzed reactions (entries 18ndash;20).11 Under such conditions compounds 2a 2b and 2c yielded to the pyrrolo- 3,2-bindole 45 (52) g-carbolines 36e (51) and 48 (73) respectively.The g-H of the organopalladium compound 42a was removed by Na2CO3 to give an anion 43a which yielded the pyrrolo3,2-bindole 45 as the result of a nucleophilic reaction and hydrogen shift (Scheme 4). For 2b and 2c (R = Pri or Bu) the intermediates 43b and 43c might undergo the palladium transfer giving the p-allylpalladium complex as 46d and 46c. Elimination of palladium and HBr followed by electrocyclization and oxidative aromatization would furnish the gcarbolines 36e and 48. Conclusions Our study of the palladium-catalyzed reactions shows three common features (i) the organopalladium compounds 9 undergo cyclization by preferential attack on the cyano group rather than at the olefinic double bonds; (ii) the iminopalladium compounds 18 and 19 undergo either the transposition of cyano groups or cyclization at the olefinic double bonds; (iii) since Et3NH1 may transfer an ethyl group to the iminopalladium compounds 34andash;d the palladium-catalyzed reactions of 2andash;d proceeded differently on replacement of Et3N by Na2CO3.Experimental Melting points are uncorrected. 1H NMR spectra were recorded at 200 or 300 MHz; 13C NMR spectra were recorded at 50 or 75 MHz TMS was used as an internal standard (J values in Hz). Mass spectra were recorded at an ionizing voltage of 70 eV. Merck silica gel 60F sheets were used for 2846 J. Chem. Soc. Perkin Trans. 1 1997 Scheme 3 N R1 PdBr CN Me N Et N Me N Me R3 R2 N Me PdBr R4 N Me N Me N Me N Me Me N Me Et N N Me Me N Me N Me N Me Me H PdBr N Me R1 NPdBr NH N Me Me N R4 N Me R3 PdBr R2 38a R2 = H R3 = Me 38b R2 = H R3= Pr 38c R2 = H R3 = Ph 38d R2 = R3= Me 34a-e 37a R2 = H R3 = Me 37b R2 = H R3= Pr 37c R2 = H R3 = Ph 37d R2 = R3= Me H-shift Pd0 39a R4 = Me 39b R4 = Pr 39d R4 = Ph ndash;Pd0 ndash;HBr Et3N for 38c and H-shift oxidative aromatization electrocyclization and oxidative aromatization electrocyclization for 34e R1 = EtCH=CH electrocyclization Et3N Et3N ndash;Pd0 ndash;HBr 40 41 36c 36a R4 = Me 36b R4 = Pr 36d R4 = Ph 36e 35 33a-e ethyl transfer from Et3NH+ for 34a-d R1 = Et Bu Bn Pri 2a-e ndash;Pd0 ndash;HBr analytical thin-layer chromatography.Column chromatography was performed on SiO2 (70ndash;230 mesh); gradients of EtOAc and hexane were used as eluents. DMF Et3N and CH2Cl2 were distilled over CaH2 whilst THF was distilled from sodium benzophenone ketyl under N2. Preparation of 2-(N-methyl-o-bromoanilino)alk-3-enenitriles 1andash;f To a mixture of N-methyl-o-bromoaniline (15.0 mmol) and aq.HCl (12 M; 12.5 ml) the appropriate unsaturated aldehyde (18 mmol) was added dropwise at 0 8C followed by aqueous KCN (1.05 g 16.2 mol 5 ml). After being stirred for 12 h at room temperature the mixture was separated the aqueous phase then being extracted with EtOAc. The combined organic phase and extracts were washed with aq. HCl (1 M) and brine dried (Na2SO4) and concentrated under reduced pressure to give the title compound; compounds 1andash;f decomposed to give aniline and aldehydes if subjected to chromatography on a silica gel column. 2-(N-Methyl-o-bromoanilino)pent-3-enenitrile 1a. Yield 59; oil; TLC EtOAcndash;hexane (2 98) Rf 0.28; nmax(neat)/cm21 2960 2801 2240 (CN) 1590 1476 970 and 760; dH(CDCl3) 1.73 (3 H ddd J 6 1 1 CHCH3) 2.65 (3 H s NCH3) 4.80 (1 H br s NCH) 6.56 (1 H ddq J 15 3 1 3-H) 6.06 (1 H dqd J 15 6 1 4-H) 6.88ndash;6.96 (1 H m ArH) 7.20ndash;7.23 (2 H m ArH) and 7.48 (1 H dd J 8 1.5 ArH); dC(CDCl3) 17.4 (q C-5) 35.0 (q NCH3) 58.3 (d C-2) 115.4 (s CN) 120.3 (s) 123.2 (d) 123.6 (d) 126.1 (d) 128.4 (d) 131.8 (d) 133.7 (d) and 147.9 (s); m/z 266 (M 1 21 28) 264 (M1 32) 185 (68) 157 (100) 105 (52) and 77 (74) (Found M 266.0238.C12H13N2Br requires M 266.0242). 2-(N-Methyl-o-bromoanilino)hept-3-enenitrile 1b. Yield 78; oil; TLC EtOAcndash;hexane (2 98) Rf 0.25; nmax(neat)/cm21 2960 2800 2240 (CN) 1590 1490 970 and 760; dH(CDCl3) 0.90 (3 H t J 7 H-7) 1.35ndash;1.50 (2 H m H-6) 2.08 (2 H dt J 7 7 H-5) 2.72 (3 H s NCH3) 4.89 (1 H br dd J 2 1 NCH) 5.57 (1 H dd J 16 2 3-H) 6.10 (1 H dtd J 16 7 1 4-H) 6.93ndash;7.02 (1 H m ArH) 7.23ndash;7.34 (2 H m ArH) and 7.55 (1 H dd J 8 1 ArH); dC(CDCl3) 13.5 (q C-7) 21.8 (t C-6) 33.9 (t C-4) 35.0 (q NCH3) 58.3 (d C-2) 115.4 (s CN) 120.3 (s) 122.5 (d) 123.2 (d) 126.1 (d) 128.4 (d) 133.6 (d) 136.9 (d) and 147.9 (s); m/z 294 (M 1 21 9) 292 (M1 11) 185 (64) 157 (100) 105 (50) and 77 (76) (Found M 292.0574.C14H17N2Br requires M 292.0575). 4-Methyl-2-(N-methyl-o-bromoanilino)pent-3-enenitrile 1c. Yield 83; oil; TLC EtOAcndash;hexane (2 98) Rf 0.29; nmax(neat)/ cm21 2920 2220 (CN) 1600 1490 770 740 and 670; dH(CDCl3) 1.68 3 H d J 1 1/2 times; C(CH3)2 1.81 3 H d J 1 1/ 2 times; C(CH3)2 2.84 (3 H s NCH3) 4.91 (1 H d J 8 NCH) 5.34 (1 H br d J 8 3-H) 6.95ndash;7.06 (1 H m ArH) 7.26ndash;7.35 (2 H m) ArH and 7.56 (1 H d J 8 ArH); dC(CDCl3) 18.6 (q C-5), J.Chem. Soc. Perkin Trans. 1 1997 2847 25.8 (q C-59) 36.6 (q NCH3) 54.0 (d C-2) 116.0 (s CN) 117.1 (s) 120.7 (s) 123.7 (d) 126.3 (d) 128.3 (d) 133.7 (d) 140.7 (s) and 148.0 (s); m/z 280 (M 1 21 7) 278 (M1 7) 265 (14) 263 (13) 185 (69) 157 (100) and 105 (51) (Found M 27.0421. C13H15N2Br requires M 278.0419). 2-(N-Methyl-o-bromoanilino)-4-phenylpent-3-enenitrile 1d. Yield 86; white solid mp 86ndash;88 8C; TLC EtOAcndash;hexane (2 98) Rf 0.20; nmax(KBr)/cm21 3054 2234 (CN) 1582 1469 968 741 and 695; dH(CDCl3) 2.78 (3 H s NCH3) 5.11 (1 H dd J 4 1 2-H) 6.32 (1 H dd J 16 4 3-H) 6.97ndash;7.08 (2 H m ArH) 7.26ndash;7.30 (5 H m ArH) 7.45 (2 H dd J 8 1 ArH) and 7.59 (1 H d J 8 ArH); dC(CDCl3) 35.4 (q NCH3) 58.6 (d C-2) 115.1 (s CN) 120.4 (s) 121.6 (d) 123.3 (d) 126.3 (d) 126.8 (2 times; d) 128.5 (d) 128.6 (d) 128.7 (2 times; d) 133.7 (d) 134.9 (d) 135.1 (s) and 147.8 (s); m/z 328 (M 1 21 7) 326 (M1 8) 247 (28) 157 (82) 142 (100) 115 (55) and 77 (14) (Found M 326.0420.C17H15N2Br requires M 326.0419). 2-(N-Methyl-o-bromoanilino)hepta-3,5-dienenitrile 1e. Yield 83; white solid mp 65ndash;67 8C; TLC EtOAcndash;hexane (2 98) Rf 0.19; nmax(KBr)/cm21 2955 2811 2230 (CN) 1595 1508 990 and 743; dH(CDCl3) 1.79 (3 H d J 7 CHCH3) 2.73 (3 H s NCH3) 4.98 (1 H d J 4 NCH) 5.66 (1 H dd J 15 4 3-H) 5.87 (1 H dq J 15 7 6-H) 6.12 (1 H dd J 15 10 5-H) 6.59 (1 H dd J 15 10 4-H) 6.97ndash;7.04 (1 H m ArH) 7.29ndash;7.31 (2 H Scheme 4 N Me NPdBr Me R1 R NPdBr N Me N R R2 Nndash; Me PdBr N Me Me N N Me NH R2 R R R2 N N Me HN N Me Me N Me NPdBr R R1 2a-c Pd0 Na2CO3 Na2CO3 H-shift electrocyclization and oxidative aromatization 45 36e R = H R2 = Et 48 R = Me R2 = H 42a R = Me R1 = H 42b R = Pr R1 = H 42c R = R1 = Me 43a 43b R = Pr R1 = H 43c R = R1 = Me 44 46b R2 = Et 46c R2 = H ndash;H+ for 42a 47b R2 = Et 47c R2 = H ndash;Pd0 ndash;Brndash; ndash;Pd0 ndash;Brndash; m ArH) and 7.57 (1 H dd J 8 ArH); dC(CDCl3) 18.1 (q C-7) 35.2 (q NCH3) 58.2 (d C-2) 115.2 (s CN) 120.3 (s) 121.8 (d) 123.2 (d) 126.1 (d) 128.4 (d) 129.4 (d) 132.9 (d) 133.7 (d) 135.2 (d) and 147.9 (s); m/z 292 (M 1 21 26) 290 (M1 29) 277 (21) 275 (20) 211 (51) 185 (74),157 (100) 106 (50) and 77 (60) (Found M 290.0417.C14H15N2Br requires M 290.0419). 2-Cyclopropyl-2-(N-methyl-o-bromoanilino)ethanenitrile 1f. Yield 78; oil; TLC EtOAcndash;hexane (5 95) Rf 0.22; nmax(neat)/ cm21 2960 2210 (CN) 1590 1480 1280 and 760; dH(CDCl3) 0.61ndash;0.83 4 H m CH(CH2)2 1.32ndash;1.43 1 H m CH(CH2)2 2.91 (3 H s NCH3) 4.15 (1 H d J 9 NCH) 6.96ndash;7.04 (1 H m ArH) 7.30 (2 H dd J 8 8 ArH) and 7.56 (1 H dd J 8 ArH); dC(CDCl3) 2.1 (t) 4.1 (t) 11.8 (d C-3) 36.1 (q NCH3) 60.2 (d C-2) 115.4 (s CN) 120.5 (s) 123.6 (d) 126.2 (d) 128.4 (d) 133.6 (d) and 147.9 (s); m/z 266 (M 1 21 68) 264 (M1 72) 240 (18) 238 (20) 225 (82) 223 (92) 186 (70) 184 (83),105 (68) 84 (7) 77 (68) and 49 (100) (Found M 264.0268.C12H13N2Br requires M 264.0262). Preparation of N-methyl-o-bromoanilinoalk-2-enenitriles 2andash;e The appropriate N-methyl-o-bromoanilinoalk-3-enenitrile was treated with ButOK (1.1 equiv.) at 0 8C in a mixture of THF (10 ml) and ButOH (2 ml). After 2 h the reaction was quenched by the addition of aqueous NH4Cl (5 ml) to the mixture which was then extracted with ethyl acetate. The combined extracts were washed with brine dried (Na2SO4) concentrated and purified by chromatography on a silica gel column with gradients of EtOAc and hexane to afford the title compounds.2-(N-Methyl-o-bromoanilino)pent-2-enenitrile 2a. Yield 64 (this compound was a mixture of two isomers E:Z = 95 5). (2E)-Isomer oil; TLC EtOAcndash;hexane (2 98) Rf 0.23; nmax(neat)/cm21 2890 2205 (CN),1603 1585 1470 750 and 720; dH(CDCl3) 1.07 (3 H t J 6 CH2CH3) 2.36 (2 H dq J 6 6 CHCH2) 3.03 (3 H s NCH3) 5.26 (1 H t J 6 3-H) 7.09 (1 H ddd J 8 8 1 ArH) 7.18 (1 H dd J 8 1 ArH) 7.33 (1 H ddd J 8 8 1 ArH) and 7.60 (1 H dd J 8 1 ArH); dC(CDCl3) 14.4 (q C-5) 22.8 (t C-4) 39.4 (q NCH3) 114.3 (s CN) 121.9 (2 times; s) 123.5 (d) 127.6 (d) 127.7 (d) 128.4 (d) 133.8 (d) and 144.8 (s); m/z 266 (M 1 21 28) 264 (M1 32) 251 (75) 249 (74) 199 (51) 169 (100) 157 (23) and 77 (70) (Found C 54.02; H 4.99; N 10.58; M 266.0238.C12H13N2Br requires C 54.54; H 4.96; N 10.61; M 266.0242); (2Z)-isomer dH(CDCl3) 0.85 (3 H t J 6 CH2CH3) 3.12 (3 H s NCH3) and 5.74 (1 H t J 6 3-H). 2-(N-Methyl-o-bromoanilino)hept-2-enenitrile 2b. Yield 62 (this compound was a mixture of two isomers E:Z = 94 6). (2E)-Isomer oil; TLC EtOAcndash;hexane (2 98) Rf 0.24; nmax(neat)/cm21 2890 2210 (CN) 1605 1590 1470 745 and 720; dH(CDCl3) 0.93 (3 H t J 7 CH2CH3) 1.30ndash;1.46 (4 H m CH2CH2CH3) 2.35 (2 H dt J 7 7 CHCH2) 3.04 (3 H s NCH3) 5.25 (1 H t J 7 3-H) 7.10 (1 H ddd J 8 8 1 ArH) 7.18 (1 H dd J 8 1 ArH) 7.33 (1 H ddd J 8 8 1 ArH) and 7.60 (1 H dd J 8 1 ArH); dC(CDCl3) 13.8 (q C-7) 22.0 (t C- 6) 29.1 (t C-5) 31.9 (t C-4) 39.5 (q NCH3) 114.4 (s CN) 121.9 (s) 122.2 (d) 122.3 (s) 127.6 (d) 127.7 (d) 128.4 (d) 133.9 (d) and 144.9 (s); m/z 294 (M 1 21 11) 292 (M1 11) 204 (100) 187 (59) 185 (61) 148 (18) and 77 (20) (Found C 57.13; H 5.89; N 9.57; M 292.0570.C14H17N2Br requires C 57.52; H 5.87; N 9.59; M 292.0575); (2Z)-isomer dH(CDCl3) 3.11 (3 H s NCH3) and 5.79 (1 H t J 7 3-H). 4-Methyl-2-(N-methyl-o-bromoanilino)pent-2-enenitrile 2c. Yield 71 (this compound was a mixture of two isomers E:Z = 91 9). (2E)-Isomer oil; TLC EtOAcndash;hexane (2 98) Rf 0.24; nmax(neat)/cm21 2960 2220 (CN) 1600 1500 1470 760 750 and 730; dH(CDCl3) 1.08 6 H d J 7 CH(CH3)2 2.72ndash;2.91 1 H m CH(CH3)2 3.03 (3 H s NCH3) 5.08 (1 H d J 10 3- H) 7.05ndash;7.20 (2 H m ArH) 7.26ndash;7.37 (1 H m ArH) and 7.60 (1 H dd J 8 1 ArH); dC(CDCl3) 23.3 2 times; q CH(CH3)2 29.6 (d C-4) 39.5 (q NCH3) 114.4 (s CN) 120.6 (s) 121.8 (s) 127.5 (d) 127.6 (d) 128.4 (d) 129.5 (d) 133.9 (d) and 144.9 (s); 2848 J.Chem. Soc. Perkin Trans. 1 1997 m/z 280 (M 1 21 20) 278 (M1 22) 265 (72) 263 (74) 199 (62) 169 (100) and 77 (24) (Found C 55.98; H 5.42; N 10.06; M 278.0421. C13H15N2Br requires C 56.11; H 5.44; N 10.09; M 278.0419); (2Z)-isomer dH(CDCl3) 3.10 (3 H s NCH3) and 5.52 (1 H t J 7 3-H). 2-(N-Methyl-o-bromoanilino)-4-phenylpent-2-enenitrile 2d. Yield 67 (this compound was a mixture of two isomers E:Z = 93 7). (2E)-Isomer oil; TLC EtOAcndash;hexane (2 98) Rf 0.17; nmax(neat)/cm21 3020 2220 (CN) 1610 1496 1020 and 690; dH(CDCl3) 3.04 (3 H s NCH3) 3.68 (2 H d J 8 PhCH2) 5.34 (1 H t J 8 3-H) 7.10 (1 H ddd J 8 8 1 ArH) 7.18ndash;7.34 (7 H m ArH) and 7.59 (1 H dd J 8 1 ArH); dC(CDCl3) 32.4 (t PhCH2) 39.4 (q NCH3) 114.2 (s CN) 119.2 (d) 119.7 (s) 122.0 (s) 126.5 (d) 127.7 (d) 127.9 (3 C d) 128.4 (2 C d) 133.8 (2 C d) 137.6 (s) and 144.7 (s); m/z 328 (M 1 21 38) 326 (M1 35) 247 (100) 169 (60) 155 (42) 91 (68) and 77 (30) (Found M 326.0410.C17H15N2Br requires M 326.0419); (2Z)-isomer dH(CDCl3) 3.16 (3 H s NCH3) and 5.92 (1 H t J 7 3-H). 2-(N-Methyl-o-bromoanilino)hepta-2,4-dienenitrile 2e. Yield 65 (this compound was a mixture of two isomers 2E:2Z = 90 10). (2E)-Isomer oil; TLC EtOAcndash;hexane (2 98) Rf 0.26; nmax(neat)/cm21 2960 2221 (CN) 1575 1476 962 764 and 725; dH(CDCl3) 1.02 (3 H t J 7.5 CH2CH3) 2.16 (2 H qdd J 7.5 7.5 1 CH2CH3) 3.11 (3 H s NCH3) 5.80 (1 H dq J 16 7.5 5- H) 5.82 (1 H d J 10 3-H) 6.38 (1 H ddq J 16 10 1 4-H) 7.12 (1 H ddd J 8 8 1 ArH) 7.20 (1 H dd J 8 1) 7.34 (1 H ddd J 8 8 1 ArH) and 7.62 (1 H dd J 8 1 ArH); dC(CDCl3) 13.5 (q CH2CH3) 26.0 (t CH2CH3) 39.6 (q NCH3) 114.4 (s CN) 119.8 (d) 120.1 (s) 122.5 (s) 125.1 (d) 128.3 (d) 128.6 (2 times; d) 134.0 (d) 137.7 (d) and 144.5 (s); m/z 292 (M 1 21 31) 290 (M1 29) 211 (100) 182 (59) and 169 (21) (Found C 57.82; H 5.23; N 9.64; M 290.0439.C14H15N2Br requires C 57.92; H 5.21; N 9.66; M 290.0419); (2Z,4E)-isomer dH(CDCl3) 3.15 (3 H s NCH3) and 6.18 (1 H dd J 9 1 3-H). Preparation of 2-alkenylamino-3-(o-bromophenyl)propanenitriles 7andash;c and 8andash;c Under an atmosphere of argon a solution of diisopropylamine (0.9 ml 5.5 mmol) in THF (10 ml) was cooled to 215 8C and a solution of BuLi (1.6 M in hexane; 3.5 ml 5.5 mmol) was added dropwise to it.After 15 min the LDA solution was cooled to 278 8C and a solution of the appropriate 2-(alkenylamino) acetonitrile (5 mmol) in THF (5 ml) was added dropwise to it. The resulting orange-coloured solution was stirred for 45 min after which a solution of o-bromobenzyl bromide (1.5 g 6 mmol) in THF (5 ml) was added dropwise to it. The reaction solution was warmed to room temperature and kept for an additional 6 h before being quenched with saturated aqueous NH4Cl. The mixture was concentrated under reduced pressure and the residue was taken up with EtOAc. The resulting solution was washed with brine dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified by chromatography on a silica gel column with gradients of EtOAc and hexane to give the title compound.2-(N-Allylanilino)-3-(o-bromophenyl)propanenitrile 7a. Yield 81; oil; TLC EtOAcndash;hexane (2 98) Rf 0.27; nmax(neat)/cm21 3050 2230 (CN) 1640 1600 1590 750 and 690; dH(CDCl3) 3.25 (1 H dd J 13 9 1/2 times; NCHCH2) 3.41 (1 H dd J 13 6.6 1/2 times; NCHCH2) 4.00 (2 H d J 6 NCH2CH CH2) 4.84 (1 H dd J 9 6.6 NCHCN) 5.23 (1 H dd J 9 1 1/2 times; NCH2CH CH2) 5.33 (1 H dd J 17 1 1/2 times; NCH2CH CH2) 5.89 (1 H ddt J 17 9 6 NCH2CH CH2) 6.96ndash;7.05 (3 H m ArH) 7.12ndash;7.36 (5 H m ArH) and 7.60 (1 H d J 8 ArH); dC(CDCl3) 38.4 (t) 52.9 (t) 53.0 (d C-2) 117.4 (s CN) 117.5 (t C CH2),118.2 (2 C d) 121.4 (d) 124.4 (s) 127.6 (d) 129.1 (2 times; d) 129.2 (d) 131.9 (d) 132.9 (d) 134.0 (d) 134.4 (s) and 147.0 (s); m/z 342 (M 1 21 4) 340 (M1 4) 171 (98) 104 (100) and 77 (65) (Found C 63.41; H 5.06; N 8.19; M 340.0569.C18H17N2Br requires C 63.52; H 5.04; N 8.24; M 340.0575). 3-(o-Bromophenyl)-2-N-(3-methylbutenyl)anilinopropanenitrile 7b. Yield 75; oil; TLC EtOAcndash;hexane (5 95) Rf 0.28; nmax(neat)/cm21 2930 2210 (CN) 1600 1500 1030 760 and 690; dH(CDCl3) 1.73 3 H d J 1 1/2 times; C(CH3)2 1.76 3 H s 1/2 times; C(CH3)2 3.22 (1 H dd J 13 9 1/2 times; NCHCH2) 3.38 (1 H dd J 13 7 1/2 times; NCHCH2) 3.85 (1 H dd J 14 6 1/2 times; NCH2CH C) 4.00 (1 H dd J 14 7 1/2 times; NCH2CH C) 4.79 (1 H dd J 9 7 NCHCN) 5.16 (1 H dd J 7 6 ArH) 6.99ndash;7.06 (3 H m ArH) 7.10ndash;7.35 (5 H m ArH) and 7.58 (1 H d J 8 ArH); dC(CDCl3) 18.1 (q) 25.8 (q) 38.6 (t) 48.6 (t) 52.9 (d C-2) 117.9 (s CN) 119.1 (2 times; d) 120.9 (d) 121.7 (d) 124.5 (s) 127.7 (d) 129.2 (3 times; d) 132.1 (d) 133.0 (d) 134.8 (s) 135.8 (s) and 147.3 (s); m/z 370 (M 1 21 14) 368 (M1 13) 344 (40) 342 (42) 199 (100) 131 (35) and 69 (81) (Found M 368.0893.C20H21N2Br requires M 368.0888). 3-(o-Bromophenyl)-2-(N-cinnamylanilino)propanenitrile 7c. Yield 83; oil; TLC EtOAcndash;hexane (2 98) Rf 0.18; nmax(neat)/ cm21 3050 2250 (CN) 1600 1500 980 760 and 690; dH(CDCl3) 3.29 (1 H dd J 14 9 1/2 times; NCHCH2) 3.48 (1 H dd J 14 7 1/2 times; NCHCH2) 4.16 (2 H d J 5.6 NCH2CH CH) 4.90 (1 H dd J 9 7 NCHCN) 6.23 (1 H dt J 16 5.6 CH CHPh) 6.66 (1 H d J 16 CH CHPh) 7.10 (1 H dd J 8 8 ArH) 7.14ndash;7.40 (12 H m ArH) and 7.57 (1 H d J 8 ArH) dC(CDCl3) 38.8 (t) 53.1 (d C-2) 53.2 (t) 117.9 (s CN) 118.8 (2 times; d) 121.9 (d) 124.7 (s) 125.8 (d) 126.5 (2 times; d) 127.8 (2 times; d) 128.6 (2 times; d) 129.5 (3 times; d) 132.2 (d) 132.8 (d) 133.2 (d) 134.8 (s) 136.6 (s) and 147.4 (s); m/z 418 (4 M 1 21 4) 416 (M1 4) 247 (12) 171 (13) 169 (13) 117 (100) 91 (22) and 77 (18) (Found C 68.99; H 5.11; N 6.70; M 416.0881.C24H21N2Br requires C 69.22; H 5.09; N 6.73; M 416.0888). 2-(N-Allyl-N-benzylamino)-3-(o-bromophenyl)propanenitrile 8a. Yield 80; oil; TLC EtOAcndash;hexane (10 90) Rf 0.39; nmax(neat)/cm21 3050 2800 2220 (CN) 1640 1500 740 and 690; dH(CDCl3) 2.98ndash;3.22 (3 H m NCHCH2 1/2 times; NCH2CH CH2) 3.36ndash;3.52 (2 H m 1/2 times; NCH2CH CH2 1/2 times; PhCH2) 4.04ndash;4.16 (2 H m NCHCN 1/2 times; PhCH2) 5.22 (1 H br d J 10 1/2 times; NCH2CH CH2) 5.30 (1 H br d J 19.5 1/2 times; NCH2CH CH2) 5.73ndash;5.84 (1 H m NCH2CH CH2) 7.10ndash;7.26 (8 H m ArH) and 7.50 (1 H dd J 8 1 ArH); dC(CDCl3) 38.1 (t) 52.9 (d) 54.2 (t) 116.8 (s CN) 118.6 (t NCH2CH CH2) 124.5 (s) 127.3 (2 times; d) 128.3 (2 times; d) 128.5 (2 times; d) 128.9 (d) 131.9 (d) 132.8 (d) 134.5 (d) 135.1 (s) and 137.5 (s); m/z 356 (M 1 21 0.3) 354 (M1 0.3),185 (79) 171 (18) 169 (19) 91 (100) and 65 (23) (Found C 64.12; H 5.41; N 7.87.C19H19BrN2 requires C 64.23; H 5.39; N 7.89). 3-(o-Bromophenyl)-2-N-(3-methylbutenyl)-N-benzylamino- propanenitrile 8b. Yield 74; oil; TLC EtOAcndash;hexane (5 95) Rf 0.27; nmax(neat)/cm21 2905 2220 (CN) 1590 1450 750 and 690; dH(CDCl3) 1.67 3 H s 1/2 times; C(CH3)2 1.75 3 H s 1/2 times; C(CH3)2 3.04ndash;3.27 (4 H m NCHCH2 NCH2CH C) 3.39 (1 H d J 14 1/2 times; CH2Ph) 4.05 (1 H d J 14 1/2 times; CH2Ph) 4.14 (1 H t J 8 NCHCN) 5.08ndash;5.18 (1 H m NCH2CH C),7.14ndash;7.36 (8 H m ArH) and 7.52 (1 H d J 8 ArH); dC(CDCl3) 18.1 (q) 25.9 (q) 38.3 (t) 49.1 (t) 52.7 (d C- 2) 55.4 (t) 117.1 (s CN) 120.5 (d) 124.5 (s) 127.3 (d) 127.4 (d) 128.3 (2 times; d) 128.6 (2 times; d) 128.9 (d) 132.0 (d),132.9 (d) 135.3 (s) 137.2 (s) and 137.9 (s); m/z 384 (M 1 21 0.3) 382 (M1 0.2) 345 (21) 343 (20) 277 (50) 275 (45) 254 (65) 171 (52) 91 (100) and 69 (85) (Found M 382.1038.C21H23N2Br requires M 382.1044). 3-(o-Bromophenyl)-2-(N-cinnamyl-N-benzylamino)propanenitrile 8c. Yield 79; oil; TLC EtOAcndash;hexane (2 98) Rf 0.17; nmax(neat)/cm21 3050 2250 1620 1500 970 750 and 690; dH(CDCl3) 3.15ndash;3.40 (3 H m NCHCH2 1/2 times; NCH2CH CH) 3.52 (1 H d J 14 1/2 times; CH2Ph) 3.66 (1 H dd J 14 4 1/2 times; NCH2CH CH) 4.05ndash;4.28 (2 H m 1/2 times; NCH2CH CH NCHCN) 6.19 (1 H ddd J 16 8 6.6 NCH2CH CH) 6.65 (1 H d J 16 NCH2CH CH) 7.14ndash;7.43 (13 H m ArH) and 7.54 (1 H d J 8 ArH); dC(CDCl3) 38.1 (t) 52.9 (d C-2) 53.6 (t) 55.5 (t) 116.8 (s CN) 124.5 (s) 125.8 (d) 126.2 (2 times; d) 127.4 J.Chem. Soc. Perkin Trans. 1 1997 2849 (2 times; d) 127.44 (d) 127.6 (d) 128.35 (d) 128.4 (2 times; d) 128.5 (2 times; d) 128.9 (d) 131.9 (d) 132.8 (d) 133.5 (d) 135.0 (s) 136.5 (s) and 137.4 (s); m/z 432 M 1 21 2) 430 (M1 2) 261 (42) 117 (100) and 91 (52) (Found M 430.1052. C25H23N2Br requires M 430.1044). General procedure for the palladium-catalyzed reactions To a stirred solution of 1 (1 mmol) in DMF (10 ml) were sequentially added Et3N (0.167 ml) PPh3 (52 mg 0.2 mmol) and Pd(OAc)2 (22.5 mg 0.1 mmol) at room temperature under an argon atmosphere. The reaction mixture was stirred and heated at 100 8C for 6ndash;8 h and then cooled to room temperature diluted with EtOAc (50 ml) washed with water (3 times; 15 ml) dried (Na2SO4) filtered and concentrated under reduced pressure. The residue was separated by chromatography on a silica gel column with gradients of EtOAc and hexane to give the products shown in Table 1.2-(Methylamino)benzonitrile 12. Solid mp 62ndash;64 8C; TLC EtOAcndash;hexane (5 95) Rf 0.13; nmax(KBr)/cm21 3280 (NH) 3020 2250 (CN),1576 1480 1210 and 743; dH(CDCl3) 2.77 (3 H d J 7 NCH3) 4.65 (1 H br s NH) 6.52 (1 H d J 8 Ph) 6.56 (1 H d J 8 Ph) and 7.28 (2 H ddd J 8 8 1 Ph); dC(CDCl3) 29.7 (q NCH3) 95.2 (s) 109.9 (d) 116.0 (d) 117.8 (s CN) 132.4 (d) 134.1 (d) and 151.0 (s); m/z 132 (M 1 21 84) 131 (100) 104 (48) and 77 (24). 9-Methyl-2-phenyl-3-(2E-phenylethenyl)-ldquor;-carboline 17. White solid mp 197ndash;199 8C; TLC EtOAcndash;hexane (5 95) Rf 0.23; nmax(KBr)/cm21 2960 1630 1496 965 815 and 750; dH(CDCl3) 3.83 (3 H s NCH3),7.21ndash;7.61 (15 H m ArH) 7.97 (1 H d J 16 ArCH CHPh) and 8.51 (1 H d J 8 ArH); dC(CDCl3) 29.1 (q NCH3) 108.7 (d) 116.7 (d) 119.8 (d) 121.4 (d) 122.3 (s) 126.6 (d) 127.0 (2 C d) 127.4 (2 times; d) 127.8 (d) 128.3(2 times; d) 128.5 (2 times; d) 130.2 (2 times; d) 131.0 (d),134.2 (s) 137.8 (s) 140.5 (s) 141.2 (s) 142.7 (s) 145.2 (s) and 151.0 (s); m/z 360 (M1 100) 359 (89) 283 (74) 268 (22) 91 (31) and 77 (75) (Found C 86.47; H 5.57; N 7.74 M 360.1634.C26H20N2 requires C 86.63; H 5.60; N 7.78; M 360.1626). N-Allyl-N-benzyl-2-(o-cyanophenyl)ethenylamine 24a. Oil; TLC EtOAcndash;hexane (2 98) Rf 0.09; nmax(neat)/cm21 3026 2214 (s CN) 1622 1588 940 753 and 698; dH(CDCl3) 3.78 (2 H dd J 6 1 NCH2CH CH2) 4.37 (2 H s CH2Ph) 5.19 (1 H dt J 9 1 1/2 times; NCH2CH CH2) 5.26 (1 H d J 14 1/2 NCH2- CH CH) 5.61 (1 H d J 14 NCH CH) 5.81 (1 H ddt J 14 9 6 NCH2CH CH2) 6.93 (1 H ddd J 8 8 1 ArH) 7.14 (1 H d J 14 NCH CH) 7.25ndash;7.38 (7 H m ArH) and 7.44 (1 H d J 8 ArH); dC(CDCl3) 53.4 (t) 55.5 (t) 93.9 (d) 107.0 (s) 118.0 (t) 119.2 (s CN) 121.7 (d) 122.6 (2 times; d) 127.5 (2 times; d) 128.9 (2 times; d) 132.2 (d) 132.6 (d) 133.0 (d) 135.0 (s) 141.7 (d) and 143.8 (s); m/z 274 (M1 10) 273 (7) 158 (7) 128 (9) 91 (100) and 65 (21) (Found C 83.01; H 6.64; N 10.18.C19H18N2 requires C 83.17; H 6.62; N 10.22). N-Benzyl-N-(3-methylbut-2-enyl)-2-(o-cyanophenyl)ethenylamine 24b. Oil; TLC EtOAcndash;hexane (2 98) Rf 0.15; nmax(neat)/ cm21 2910 2205 (s CN) 1620 1590 940 760 and 697; dH(CDCl3) 1.61 3 H d J 1 1/2 times; C(CH3)2 1.74 3 H d J 1 1/2 times; C(CH3)2 3.75 (2 H d J 7 NCH2CH C) 4.33 (2 H s CH2Ph) 5.21 (1 H br d J 7 NCH2CH C) 5.58 (1 H d J 14 NCH CH) 6.90 (1 H ddd J 8 8 1 ArH) 7.15 (1 H d J 14 NCH CH) 7.24ndash;7.36 (7 H m ArH) and 7.42 (1 H dd J 8 1 ArH); dC(CDCl3) 17.8 (q) 25.6 (q) 48.3 (t) 55.3 (t) 93.2 (d) 106.7 (s) 119.2 (d) 121.4 (d) 122.2 (d) 127.3 (d) 127.32 (s) 127.4 (2 times; d) 128.5 (2 times; d) 132.1 (d) 132.9 (d) 136.5 (s) 137.5 (s) 141.9 (d) and 143.9 (s); m/z 302 (M1 16) 233 (24) 106 (30) 91 (100) and 69 (57) (Found M 302.1786.C21H22N2 requires M 302.1783). N-Benzyl-N-cinnamyl-2-(o-cyanophenyl)ethenylamine 24c. Oil; TLC EtOAcndash;hexane (5 95) Rf 0.09; nmax(neat)/cm21 3030 2210 (s CN) 1620 1590 750 and 697; dH(CDCl3) 3.96 (2 H d J 6 NCH2CH CH) 4.44 (2 H s CH2Ph) 5.73 (1 H d J 14 NCH CH) 6.18 (1 H dt J 16 6 NCH2CH CH) 6.55 (1 H d J 16 NCH2CH CH) 6.94 (1 H ddd J 8 8 1 ArH) and 7.20ndash; 7.53 (14 H m ArH); dC(CDCl3) 52.8 (t) 55.2 (t) 93.8 (d) 106.8 (s) 119.1 (s CN) 121.5 (d) 122.4 (d) 123.9 (d) 126.3 (2 times; d) 127.4 (3 times; d) 127.6 (d) 128.4 (2 times; d) 128.5 (2 times; d) 132.1 (d) 132.7 (d) 133.1 (d) 136.2 (s) 137.1 (s) 141.6 (d) and 143.5 (s); m/z 350 (M1 6) 128 (9) 117 (84) and 91 (100) (Found C 85.41; H 6.35; N 8.02; M 350.1772.C25H22N2 requires C 85.67; H 6.33; N 8.00; M 350.1783). N-(3-Methylbut-2-enyl)aniline 26b. Oil; TLC EtOAcndash;hexane (1 99) Rf 0.10; nmax(neat)/cm21 3400 (NH) 2905 1600 1490 760 and 695; dH(CDCl3) 1.87 3 H s 1/2 times; C(CH3)2 1.91 3 H s 1/2 times; C(CH3)2 3.66 (1 H br s NH) 3.82 (2 H d J 6.6 NCH2CH C) 5.48 (1 H t J 6 NCH2CH C) 6.76 (2 H d J 8 Ph) 6.86 (1 H dd J 8 8 Ph) and 7.36 (2 H dd J 8 8 Ph); dC(CDCl3) 18.5 (q) 26.2 (q) 42.5 (t) 113.4 (2 times; d) 117.8 (d) 122.3 (d) 129.7 (2 times; d) 135.9 (s) and 149.0 (s); m/z 161 (M1 36) 146 (23) 106 (37) 93 (100) 77 (52) and 69 (64) (Found M 161.1213.C11H15N requires M 161.1204). N-Cinnamylaniline 26c. Oil; TLC EtOAcndash;hexane (1 99) Rf 0.07; nmax(neat)/cm21 3400 (NH) 3020 1625 1590 1500 963 760 and 695; dH(CDCl3) 3.57 (1 H br s NH) 3.96 (2 H dd J 6 1.4 NCH2CH CH) 6.36 (1 H dt J 16 6 NCH2CH CH) 6.66 (1 H d J 16 NCH2CH CH) 6.70ndash;6.74 (2 H m Ph) 6.77 (1 H ddd J 8 8 1 Ph) and 7.22ndash;7.42 (7 H m Ph); dC(CDCl3) 46.1 (t) 113.0 (2 times; d) 117.5 (d) 126.3 (2 times; d) 127.0 (d) 127.4 (d) 128.5 (2 times; d) 129.2 (2 times; d) 131.4 (d) 136.8 (s) and 148.0 (s); m/z 209 (M1 78) 117 (100) 91 (30) 65 (20) and 51 (14) (Found M 209.1219. C15H15N requires M 209.1204). 4-Cyano-1-methylene-3-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine 29a. Solid mp 115ndash;117 8C; TLC EtOAcndash;hexane (5 95) Rf 0.28; nmax(KBr)/cm21 3030 2220 (CN) 1590 1500 760 and 695; dH(CDCl3) 3.18 (1 H dd J 14 5 1/2 times; NCHCH2) 3.51 (1 H dd J 14 12 1/2 times; NCHCH2) 4.35 (1 H d J 20 1/2 times; NCH2) 4.49 (1 H dd J 12 5 NCHCH2) 4.61 (1 H ddd J 20 2 2 1/2 times; NCH2) 5.34 (1 H dd J 2 2 1/2 times; C CH2) 5.51 (1 H dd J 2 2 1/2 times; C CH2) 6.72ndash;6.82 (3 H m ArH) 7.11ndash;7.24 (5 H m ArH) and 7.45 (1 H dd J 8 1 ArH); dC(CDCl3) 38.6 (t) 51.05 (d) 51.10 (t) 113.1 (t) 113.8 (2 times; d) 118.6 (s) 119.4 (d) 127.8 (d) 128.4 (2 times; d) 129.3 (3 times; d) 132.6 (s) 139.6 (s) 148.6 (s) and 148.8 (s); m/z 260 (M1 54) 259 (35) 245 (34) 129 (71) 115 (85) and 77 (100) (Found C 82.95; H 6.23; N 10.75.C18H16N2 requires C 83.03; H 6.20; N 10.77). 4-Cyano-1-phenylmethylene-3-phenyl-2,3,4,5-tetrahydro-1H- 3-benzazepine 29c.Oil; TLC EtOAcndash;hexane (1 99) Rf 0.04; nmax(neat)/cm21 3010 2905 2210 (CN) 1590 1500 760 and 690; dH(CDCl3) 3.23 (1 H dd J 14 5.5 1/2 times; NCHCH2) 3.53 (1 H dd J 14 12 1/2 times; NCHCH2) 4.53 (1 H dd J 12 5.5 NCHCH2) 4.73 (2 H d J 2 NCH2) 6.67 (1 H dd J 8,1 ArH) 6.78 (1 H ddd J 8 8 1 ArH) 6.92 (1 H d J 2 C CHPh) 7.14ndash;7.31 (11 H m ArH) and 7.47 (1 H dd J 8 1); dC(CDCl3) 38.4 (t) 49.5 (t) 51.4 (d) 114.2 (2 times; d) 118.7 (s) 119.6 (d),127.3 (d) 127.6 (d) 128.0 (d) 128.4 (d) 128.6 (2 times; d) 128.7 (d) 129.2 (4 times; d) 129.8 (d) 132.9 (s) 136.5 (s) 141.5 (s) 142.0 (s) 148.6 (s); m/z 336 (M1 35) 245 (52) 128 (30) 115 (32) 104 (50) 91 (100) and 77 (84) (Found C 85.50; H 6.03; N 8.37. C24H20N2 requires C 85.67; H 6.00; N 8.33). 2,3-Dihydro-1-methylene-3-phenyl-1H-3-benzazepine 31a. Oil TLC EtOAcndash;hexane (10 90) Rf 0.53; nmax(neat)/cm21 2930 1630 1600 1350 760 and 690; dH(CDCl3) 4.34 (2 H s NCH2) 4.96 (1 H d J 1 1/2 times; C CH2) 5.42 (1 H d J 1 1/2 times; C CH2) 5.62 (1 H d J 9.5 NCH CH) 6.54 (1 H d J 9.5 NCH CH) and 6.99ndash;7.42 (9 H m ArH); dC(CDCl3) 54.8 (t) 106.3 (d) 114.3 (t) 119.5 (2 times; d) 122.1 (d) 124.1 (d) 127.5 (d) 127.6 (d) 129.3 (2 times; d) 129.7 (d) 134.6 (d) 134.62 (s) 138.2 (s) 143.4 (s) and 146.0 (s); m/z 233 (M1 43) 232 (32) 141 (17) 130 (23) 115 (31) 104 (62) and 77 (100) (Found M 233.1198.C17H15N requires M 233.1204) (Found C 87.45; H 6.50; N 6.04. C17H15N requires C 87.51; H 6.48; N 6.01). 3-Benzyl-2,3-dihydro-1-methylene-1H-3-benzazepine 32a. Oil; 2850 J. Chem. Soc. Perkin Trans. 1 1997 TLC EtOAcndash;hexane (2 98) Rf 0.32; nmax(neat)/cm21 3026 1619 1591 1487 765 and 697; dH(CDCl3) 3.58 (2 H s NCH2) 4.19 (2 H s NCH2Ph),4.75 (1 H s 1/2 times; C CH2) 5.23 (1 H d J 9 NCH CH) 5.40 (1 H s 1/2 times; C CH2) 6.25 times; (1 H d J 9 NCH CH) 6.95 (1 H dd J 8 8 ArH) 7.07ndash;7.15 (2 H m ArH) and 7.24ndash;7.34 (6 H m ArH); dC(CDCl3) 55.2 (t) 59.6 (t) 100.5 (d) 114.1 (t) 123.0 (d) 127.4 (d) 127.5 (2 times; d) 128.0 (2 times; d) 128.5 (2 times; d) 128.9 (d) 135.7 (s) 137.6 (s) 138.0 (s) 138.1 (d) and 143.8 (s); m/z 247 (M1 36) 156 (22) 91 (100) 77 (14) and 65 (25) (Found C 87.32; H 6.97; N 5.70; M 247.3385.C18H17N requires C 87.41; H 6.93; N 5.66; M 247.3397). 2,8,9-Trimethyl-ldquor;-carboline 36a. Solid mp 97ndash;98 8C; TLC EtOAcndash;hexane (5 95) Rf 0.11; nmax(KBr)/cm21 3050 1615 1598 and 1490; dH(CDCl3) 2.41 (3 H s ArCH3) 2.66 (3 H s ArCH3) 3.66 (3 H s NCH3) 7.23ndash;7.32 (3 H m ArH) 7.48 (1 H dd J 8 8 ArH) and 8.37 (1 H d J 8 ArH); dC(CDCl3) 20.3 (q ArCH3) 22.5 (q ArCH3) 28.7 (q NCH3) 108.4 (d) 116.5 (d) 119.2 (d) 120.3 (d) 121.7 (2 times; s) 125.6 (d) 128.3 (s) 133.4 (s) 141.2 (s) and 148.8 (s); m/z 211 (M 1 11 24) 210 (100 M1) 209 (56) and 195 (75) (Found C 80.03; H 6.69; N 13.29 M 210.1156.C13H12N2 requires C 79.96; H 6.72; N 13.33; M 210.1157). 3,9-Dimethyl-2-propyl-ldquor;-carboline 36b. Solid mp 71ndash;73 8C; TLC EtOAcndash;hexane (5 95) Rf 0.07; nmax(KBr)/cm21 3050 1610 1600 and 1490; dH(CDCl3) 1.08 (3 H t J 7 CH2CH3) 1.66ndash;1.84 (2 H m ArCH2CH2) 2.76 (3 H s NCH3) 2.79 (2 H d J 7.6 ArCH2) 3.81 (3 H s NCH3) 7.33 (1 H ddd J 8 8 1 ArH) 7.40ndash;7.42 (2 H m ArH) 7.52 (1 H ddd J 8 8 1 ArH) and 8.41 (1 H dd J 8 1 ArH); dC(CDCl3) 14.0 (q CH2CH3) 22.2 (q ArCH3) 23.4 (t) 28.9 (q NCH3) 35.8 (t ArCH2) 108.5 (d) 115.9 (d) 119.3 (d) 120.5 (d) 121.8 (s) 126.7 (d) 132.8 (s) 133.5 (s) 138.8 (s) 141.5 (s) and 148.5 (s); m/z 238 (M1 46) 209 (100) 193 (18) and 57 (42) (Found C 80.55; H 7.64; N 11.73; M 238.1478.C16H18N2 requires C 80.62; H 7.62; N 11.76; M 238.1470). 9-Methyl-1-isopropyl-ldquor;-carboline 36c. Oil; TLC EtOACndash; hexane (15 85) Rf 0.23; nmax(neat)/cm21 2967 1612 1572 1479 750 and 740; dH(CDCl3) 1.43 6 H d J 7 CH(CH3)2 3.73ndash;3.90 1 H m ArCH(CH3)2 4.03 (3 H s NCH3) 7.20ndash;7.31 (2 H m ArH) 7.37 (1 H d J 8 ArH) 7.50 (1 H ddd J 8 8 1 ArH) 8.36 (1 H dd J 8 1 ArH) and 8.45 (1 H d J 8 ArH); dC(CDCl3) 23.5 2 times; q 2 times; CH(CH3)2 27.7 (d ArCH) 32.4 (q NCH3) 108.6 (d) 116.9 (d) 119.6 (d) 120.5 (d) 122.0 (s) 127.4 (d) 129.5 (s) 132.0 (s) 140.0 (s) 141.9 (d) and 142.3 (s); m/z 224 (M1 100) 209 (97) 194 (73) 181 (13) and 104 (14) (Found C 80.25; H 7.22; N 12.46; M 224.1324.C15H16N2 requires C 80.31; H 7.19; N 12.50; M 224.1313). 3,9-Dimethyl-2-phenyl-ldquor;-carboline 36d. Solid mp 132ndash; 134 8C; TLC EtOAcndash;hexane (2 98) Rf 0.10; nmax(KBr)/cm21 3048 1620 1593 1487 747 and 702; dH(CDCl3) 2.65 (3 H s ArCH3) 3.55 (3 H s NCH3) 7.20 (1 H dd J 8 1 ArH) 7.25 (1 H dd J 8,1 ArH) 7.33ndash;7.46 (7 H m ArH) and 8.40 (1 H d J 8 ArH); dC(CDCl3) 23.3 (q ArCH3) 28.6 (q NCH3) 108.4 (d) 116.5 (d) 119.3 (d) 120.5 (d) 121.4 (s) 127.0 (2 times; d) 128.1 (2 times; d) 129.2 (2 times; d) 132.7 (s) 133.7 (s) 139.9 (s) 141.2 (s) 141.7 (s) and 147.3 (s); m/z 272 (M1 100) 271 (52) 256 (14) and 128 (12) (Found C 83.66; H 5.97; N 10.34; M 272.1298. C19H16N2 requires C 83.78; H 5.93; N 10.29; M 272.1313).3-Ethyl-9-methyl-ldquor;-carboline 36e. Oil; TLC EtOAcndash;hexane (10 90) Rf 0.25; nmax(neat)/cm21 2961 1620 1475 1410 845 817 and 749; dH(CDCl3) 1.40 (3 H t J 7.5 CH2CH3) 3.02 (2 H q J 7.5 ArCH2) 3.75 (3 H s NCH3) 7.21 (1 H d J 8 ArH) 7.27 (1 H dd J 8 8 ArH) 7.35 (1 H d J 8 ArH) 7.50 (1 H dd J 8,1 ArH) 7.54 (1 H dd J 8 1 ArH) and 8.41 (1 H dd J 8 1 ArH); dC(CDCl3) 15.0 (q CH2CH3) 28.8 (t ArCH2) 31.4 (q NCH3) 108.5 (d) 115.8 (d) 118.6 (d) 119.3 (d) 120.8 (d) 121.8 (s) 127.2 (d) 132.7 (s) 141.0 (s) 141.6 (s) and 155.4 (s); m/z 211 (M 1 11 23) 210 (M1 100) 209 (54) and 195 (25) (Found C 79.80; H 6.75; N 13.37; M 210.1155. C14H14N2 requires C 79.96; H 6.72; N 13.33; M 210.1157). 3,8-Dihydro-2,8-dimethylpyrrolo3,2-bindole 45. Solid mp 162ndash;164 8C; TLC EtOAcndash;hexane (5 95) Rf 0.13; nmax(KBr)/ cm21 3040 (NH) 3010 1600 1495 and 740; dH(CDCl3) 2.45 (3 H d J 0.6 ArCH3) 3.76 (3 H s NCH3) 5.91 (1 H q J 0.6 ArH) 7.07ndash;7.20 (2 H m ArH) 7.30 (1 H dd J 8 1 ArH) 7.53 (1 H dd J 8 1 ArH) and 7.85 (1 H br s NH); dC(CDCl3) 14.3 (q) 30.8 (q NCH3) 89.1 (d) 108.8 (d) 115.3 (s) 115.6 (d) 117.6 (d) 118.0 (s) 119.3 (d) 132.2 (s) 136.1 (s) and 140.1 (s); m/z 184 (M1 100) 183 (93) 169 (20) 168 (24) 102 (9) and 91 (13) (Found C 78.28; H 6.54; N 15.18.C12H12N2 requires C 78.22; H 6.57; N 15.21). 2,9-Dimethyl-ldquor;-carboline 48. Solid mp 84ndash;86 8C; TLC EtOAcndash;hexane (5 95) Rf 0.11; nmax(KBr)/cm21 2960 1610 1580 750 and 740; dH(CDCl3) 2.37 (3 H s ArCH3) 3.50 (3 H s NCH3) 7.13ndash;7.22 (3 H m ArH) 7.38 (1 H ddd J 8 8 1 ArH) 8.22 (1 H s ArH) and 8.24 (1 H dd J 8 1 ArH); dC(CDCl3) 19.0 (q ArCH3) 28.4 (q NCH3) 108.5 (d) 115.3 (d) 119.4 (d) 120.2 (d) 121.7 (s) 126.8 (d) 129.5 (s) 134.2 (s) 139.3 (s) 141.4 (s) and 142.2 (d); m/z 197 (M 1 11 35) 196 (M1 99) 195 (100) 181 (31) 167 (15) 153 (12) and 98 (21) (Found C 79.47; H 6.20; N 14.24; M 196.0989.C13H12N2 requires C 79.55; H 6.17; N 14.28; M 196.1000). Acknowledgements We thank the National Science Council of the Republic of China for financial support (Grant NSC 83-0208-M041-006) and Prof. Jim-Min Fang (National Taiwan University) for helpful discussions. References 1 (a) R. F. Heck Palladium Reagents in Organic Syntheses Academic Press London 1985; (b) R. F. Heck Org. React. 1982 27 345; (c) G. D. Davis Jr. and A. Hallberg Chem. Rev. 1989 89 1433; (d ) R. F. Heck Acc. Chem. Res. 1979 12 146. 2 (a) C.-C. Yang P.-J.Sun and J.-M. Fang J. Chem. Soc. Chem. Commun 1994 2629; (b) C.-C. Yang H.-M. Tai and P.-J. Sun Synlett 1997 in press. 3 S. B. Kadin J. Org. Chem. 1973 38 1348. 4 (a) J.-M. Fang L.-F. Liao and C.-C. Yang Proc. Natl. Sci. Council (Taipei) 1985 9 1; (b) J.-M. Fang C.-C. Yang and Y.-W. Wang J. Org. Chem. 1989 54 477. 5 (a) B. Costisella and H. Gross Tetrahedron 1982 38 139; (b) N. Stevenart-De Mesmaeker R. Merenyi and H. G. Viehe Tetrahedron Lett. 1987 28,2591; (c) J.-M. Fang and C.-J. Chang J. Chem. Soc. Chem. Commun. 1989 1787. 6 (a) J.-M. Fang C.-C. Yang and Y.-W. Wang J. Org. Chem. 1989 54 481; (b) H. J. Jeng and J. M. Fang J. Chin. Chem. Soc. 1994 41 803. 7 J.-M. Fang and C.-C. Yang J. Chem. Soc. Chem. Commun. 1985 1356; (b) C.-C. Yang and J.-M. Fang J. Chem. Soc. Perkin Trans.1 1992 3085. 8 W. Cabri I.Candiani and A. Bedeschi J. Org. Chem. 1992 57 3558. 9 A. Couture E. Deniau Y. Gimbert and P. Grandclaudon Tetrahedron 1993 49 1431. 10 R. A. Abramovich Can. J. Chem. 1960 38 2273. 11 (a) H. Yoshizaki H. Satoh Y. Sato S. Nukui M. Shibasaki and M. Mori J. Org. Chem. 1995 60 2016; (b) L. Besson J. Bazin and B. Cazes Tetrahedron Lett. 1994 35 2881; (c) C. S. Nylund and S. M. Weinreb Tetrahedron Lett. 1994 35 4287. Paper 7/02710I Received 21st April 1997 Accepted 18th June 1997 J. Chem. Soc. Perkin Trans. 1 1997 2843 Palladium-catalyzed chemoselective intramolecular cyclization of bromoanilinoalkenenitriles Chau-Chen Yang,* Huo-Mu Tai and Pei-Jiun Sun Department of Cosmetic Science Chia Nan College of Pharmacy and Science Tainan 717 Taiwan Republic of China middot;-(o-Bromoanilino)alkenenitriles 1andash;f and 2andash;e and middot;-(N-alkenylamino)-lsquor;-(o-bromophenyl)- propanenitriles 7andash;c and 8andash;c undergo palladium-catalyzed conversion into o-(methylamino)benzonitrile 12 o-(alkenylamino)ethenylbenzonitriles 24andash;c N-alkenylanilines 26b 26c 3-benzazepines 29a 29c 31a and 32a ldquor;-carbolines 36 and pyrrolo3,2-bindole 45.The reactions involve intramolecular additions of arylpalladium to the cyano group and subsequent processes such as cyano group transposition hydrolysis electrocyclization ethyl group transfer and oxidative aromatization. A general mechanism for the palladium-catalyzed arylation of a cyano group is proposed. Introduction Heck reactions are important palladium-catalyzed reactions for carbonndash;carbon bond formation such as the well documented arylation of olefins;1 the corresponding arylation of a cyano group is however unprecedented except for a previous report from our group.2 A series of N-methyl-(o-bromoanilino)alk-3- enenitriles 1andash;e 2-anilino-2-cyclopropylacetonitrile 1f Nmethyl-( o-bromoanilino)alk-2-enenitriles 2andash;e and Nalkenylamino- 3-(o-bromophenyl)propanenitriles 7andash;c 8andash;c have been prepared and their intramolecular palladiumcatalyzed cyclizations studied.2 Most of these compounds have olefin and cyano groups oriented in similar proximity to the arylpalladium complex.The palladium-catalyzed cyclization may occur by two competitive pathways namely by attack on the olefinic function or on the cyano group. This study indicates that the palladium-catalyzed arylation occurs in most cases selectively at the cyano group to afford o-(methylamino)- benzonitrile 12 o-(alkenylamino)ethenylbenzonitriles 24 Nalkenylanilines 26 g-carbolines 36 and pyrrolo3,2-bindole 45.Results and discussion Non-conjugated a-(o-bromoanilino)alkenenitriles 1andash;e were prepared eqn. (1) by condensation of equimolar amounts of an appropriate unsaturated aldehyde potassium cyanide and N-methyl-o-bromoaniline 3 in the presence of hydrochloric acid (12 M).4 a-Amino(cyclopropyl)acetonitrile 1f was similarly prepared from cyclopropanecarbaldehyde. Treatment of 1andash;e with a strong base But-OK in ButOHndash;THF at 0 8C for 2 h gave the thermodynamically favoured conjugated a-aminoalkenenitriles 2andash;e predominantly as the 2E-isomer (E:Z 10).5 2-(Alkenylamino) acetonitriles 5andash;c 6andash;c prepared from N-alkylations of a-aminonitriles 3 and 4,6 were treated with lithium diisopropylamide (LDA) and o-bromobenzyl bromide to give 2-(alkenylamino)-3-(o-bromophenyl)propanenitriles 7andash;c and 8andash;c eqn.(2).7 In a typical procedure 8 (Table 1) a-(o-bromoanilino) alkenenitrile 1d (1 mmol) in DMF (15 ml) was treated with Pd(OAc)2 (0.1 mmol) PPh3 (0.2 mmol) and Et3N (1.2 mmol) for 6 h at 100 8C under an argon atmosphere to give 2- (methylamino)benzonitrile 12 and g-carboline 17 in 38 and 36 yields respectively. The reactions of 1andash;c e f gave the benzonitrile 12 (60ndash;85) and aldehydes RCHO. A possible mechanism for the palladium-catalyzed reactions 9 is illustrated by the formation of the benzonitrile 12 (Scheme 1). The reactions were presumably initiated by oxidative insertion of Pd0 into the bromophenyl groups.The organopalladium 9 undergoing cyclisation by attack on the cyano group giving 10 but not the olefinic double bonds. The iminoindoline 10 might CN Cl CN CN NMe R R1 NMe CN NH R Br R1 R2 CN N R1 R2 R Br Br NHMe Br Br Br R H O N CN Br R R1 R2 + RNH2 7a R = Ph R1 = R2 = H 7b R = Ph R2 = R2 = Me 7c R = R1 = Ph R2 = H 8a R= Bn R1 = R2 = H 8b R = Bn R1 = R2 = Me 8c R = Bn R1 = Ph R2 = H 5a R = Ph R1 = R2 = H 5b R = Ph R1 = R2 = Me 5c R = R1 = Ph R2= H 6a R= Bn R1 = R2 = H 6b R = Bn R1 = R2 = Me 6c R = Bn R1 = Ph R2 = H 3 R = Ph 4 R = Bn 2 CH2Cl2 40 oC Et3N/CH2Cl2 40 oC Et3N (2) 2a R1 = Et 2b R1 = Bu 2c R1 = Pri 2d R1 = Bn 2e R1 = EtCH=CH 1a R = MeCH=CH 1b R = PrCH=CH 1c R = Me2C=CH 1d R = PhCH=CH 1e R = MeCH=CHCH=CH 1f R = (CH2)2CH ButOH/THF 0 oC 2 h ButOK KCN(aq.) 12 N HCl + (1) 1 LDA/THF 2844 J.Chem. Soc. Perkin Trans. 1 1997 Scheme 1 N Me R CN PdBr N NPdBr Me CN N R Me CN NHMe N N Me N+ Ph Ph PdBr N+ PdBr N Br N CN R Me R N Ph Ph Me PdBr Ph Ph H N Me Ph NH PdBr Ph N Me Ph N Me H H 1a-f PdII(OAc)2 PPh3/DMF Pd0L2 (L = PPh3) + R = PhCH=CH + PhCH=CHCHO + RCHO 12 13 9 10 11 Et3N For 10d 14 17 Brndash; H2O H-shift electrocyclization H-shift Et3N ndash;Pd0 ndash;HBr 15 16 Table 1 Palladium-catalyzed chemoselective intramolecular cyclization of bromoanilinoalkenenitriles a Reaction Products (yield ) b Entry 123456789 10 11 12 13 14 15 16 17 18 19 20 Substrate 1a 1b 1c 1d 1e 1f 7a 7b 7c 8a 8b 8c 2a 2b 2c 2d 2e 2a 2b 2c Base Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Et3N Na2CO3 Na2CO3 Na2CO3 time (h) 66666688888866666 12 12 12 Addition to CN 12 (81) 12 (60) 12 (85) 12 (38) 1 17 (36) 12 (72) 12 (80) mdash; 26b (76) 26c (66) 24a (9) 24b (78) 24c (72) 36a (88) 36b (73) 36c (85) 36d (63) 36e (75) 45 (52) 36e (51) 48 (73) Addition to C C mdash;mdash;mdash;mdash;mdash;mdash; 29a (60) 1 31a (18) mdash; 29c (16) 32a (77) mdash;mdash;mdash;mdash;mdash;mdash;mdash;mdash;mdash;mdash; a The reactions were run under an argon atmosphere with 1 equiv.of bromoanilinoalkenenitrile 1.2 equiv of base 20 mol of PH3P and 10 mol of Pd(OAc)2 in DMF at 100 8C. b Isolated yields after purification. yield an iminium ion 11 which is subsequently hydrolyzed to give 2-(methylamino)benzonitrile 12 and aldehydes RCHO. When R is a styryl group the palladium amide 10d reacted further with cinnamaldehyde to give g-carboline 17.10 This process might involve electrocyclization H-shift and elimination of palladium and HBr. Under similar reaction conditions the palladium-catalyzed reactions of 2-(alkenylamino)-3-(o-bromophenyl)propanenitrile 7b afforded the alkenylamine 26b (76).This result was explained in terms of the organopalladium compound (18 and 19) attacking the cyano group selectively (Scheme 2). Thus the benzonitrile iminium salts (22 and 23) generated from the J. Chem. Soc. Perkin Trans. 1 1997 2845 Scheme 2 N R CN R1 PdBr N R R1 CN R1 N R N R1 CN PdBr R R2 NPdBr N R1 R R2 N CN R R1 R2 N R1 CN R R2 CHO CN HN R1 R2 R ndash;Pd0 ndash;HBr ndash;H+ ndash;Brndash; Et3Nndash;DMF 100 oC Pd(OAc)2ndash;PPh3 + 25 for 18b c and19a-c for 18a c and 19a ndash;HCN 29a R = Ph R1 = H 29c R = R1 = Ph 30a R= Bn R1 = H 31a R = Ph R1 = H 32a R = Bn R1 = H 26b R = Ph R1 = R2 = Me 26c R = R1 =Ph R2 = H 24a R = Bn R1 = R2 = H 24b R = Bn R1 = R2 = Me 24c R = Bn R1 = Ph R2 = H 22 R = Ph 23 R = Bn 20 R = Ph 21 R = Bn 27a R = Ph R1 = H 27c R = R1 = Ph 28a R = Bn R1 = H 18a R = Ph R1 = R2 = H 18b R = Ph R1 = R2 = Me 18c R = R1 = Ph R2 = H 19a R = Bn R1 = R2 =H 19b R = Bn R1 = R2 = Me 19c R = Bn R1 = Ph R2 = H H2O ndash;Pd0 Et3N (ndash;Pd0 ndash;HBr) + 7a-c 8a-c R2 = H iminoindoline intermediates (20 and 21) upon elimination of HBr would give the aminovinylbenzonitriles 24 or undergo hydrolysis to give the alkenylamines 26b c.On the other hand analogous organopalladium compounds (18a c) might attack the less hindered double bonds as shown in the transformation of 7a and 7c to 3-benzazepine derivatives 29a (60) and 29c (16). The reactions of 8andash;c followed similar pathways the organopalladium intermediate attacking either the cyano group or the olefinic double bond depending on the nature of the substrates.At elevated reaction temperatures elimination of HCN from 29a and 30a occurred to give the benzazepines 31a and 32a. The palladium-catalyzed reactions of the conjugated bromoanilinoalkenenitriles 2andash;e (as E/Z-mixtures) afforded gcarbolines 36andash;e (63ndash;88 entries 13ndash;17). The organopalladium compound 34e (R1 = butenyl) had the potential to undergo 6p electrocyclization and subsequent elimination of palladium and HBr to produce the g-carboline 36e (Scheme 3). Although the intermediates 34a b d derived from 2a b d (R = Et Bu Bn) could not undergo electrocyclization capture of an ethyl group from Et3NH1 would give 38a b d. Subsequent elimination of palladium and HBr followed by electrocyclization and oxidative aromatization would furnish the g-carbolines 36a b d.The intermediate 34c derived from 2c (R = Pri) underwent electrocyclization in a different way via 40 to furnish the 4-isopropyl-gcarboline 36c. In order to determine whether the ethyl group was transferred from Et3N in the conversion of 2andash;c into g-carbolines 36andash;c we replaced Et3N with Na2CO3 (1.2 equiv.) as the base in the palladium-catalyzed reactions (entries 18ndash;20).11 Under such conditions compounds 2a 2b and 2c yielded to the pyrrolo- 3,2-bindole 45 (52) g-carbolines 36e (51) and 48 (73) respectively. The g-H of the organopalladium compound 42a was removed by Na2CO3 to give an anion 43a which yielded the pyrrolo3,2-bindole 45 as the result of a nucleophilic reaction and hydrogen shift (Scheme 4). For 2b and 2c (R = Pri or Bu) the intermediates 43b and 43c might undergo the palladium transfer giving the p-allylpalladium complex as 46d and 46c.Elimination of palladium and HBr followed by electrocyclization and oxidative aromatization would furnish the gcarbolines 36e and 48. Conclusions Our study of the palladium-catalyzed reactions shows three common features (i) the organopalladium compounds 9 undergo cyclization by preferential attack on the cyano group rather than at the olefinic double bonds; (ii) the iminopalladium compounds 18 and 19 undergo either the transposition of cyano groups or cyclization at the olefinic double bonds; (iii) since Et3NH1 may transfer an ethyl group to the iminopalladium compounds 34andash;d the palladium-catalyzed reactions of 2andash;d proceeded differently on replacement of Et3N by Na2CO3.Experimental Melting points are uncorrected. 1H NMR spectra were recorded at 200 or 300 MHz; 13C NMR spectra were recorded at 50 or 75 MHz TMS was used as an internal standard (J values in Hz). Mass spectra were recorded at an ionizing voltage of 70 eV. Merck silica gel 60F sheets were used for 2846 J. Chem. Soc. Perkin Trans. 1 1997 Scheme 3 N R1 PdBr CN Me N Et N Me N Me R3 R2 N Me PdBr R4 N Me N Me N Me N Me Me N Me Et N N Me Me N Me N Me N Me Me H PdBr N Me R1 NPdBr NH N Me Me N R4 N Me R3 PdBr R2 38a R2 = H R3 = Me 38b R2 = H R3= Pr 38c R2 = H R3 = Ph 38d R2 = R3= Me 34a-e 37a R2 = H R3 = Me 37b R2 = H R3= Pr 37c R2 = H R3 = Ph 37d R2 = R3= Me H-shift Pd0 39a R4 = Me 39b R4 = Pr 39d R4 = Ph ndash;Pd0 ndash;HBr Et3N for 38c and H-shift oxidative aromatization electrocyclization and oxidative aromatization electrocyclization for 34e R1 = EtCH=CH electrocyclization Et3N Et3N ndash;Pd0 ndash;HBr 40 41 36c 36a R4 = Me 36b R4 = Pr 36d R4 = Ph 36e 35 33a-e ethyl transfer from Et3NH+ for 34a-d R1 = Et Bu Bn Pri 2a-e ndash;Pd0 ndash;HBr analytical thin-layer chromatography.Column chromatography was performed on SiO2 (70ndash;230 mesh); gradients of EtOAc and hexane were used as eluents. DMF Et3N and CH2Cl2 were distilled over CaH2 whilst THF was distilled from sodium benzophenone ketyl under N2. Preparation of 2-(N-methyl-o-bromoanilino)alk-3-enenitriles 1andash;f To a mixture of N-methyl-o-bromoaniline (15.0 mmol) and aq. HCl (12 M; 12.5 ml) the appropriate unsaturated aldehyde (18 mmol) was added dropwise at 0 8C followed by aqueous KCN (1.05 g 16.2 mol 5 ml). After being stirred for 12 h at room temperature the mixture was separated the aqueous phase then being extracted with EtOAc.The combined organic phase and extracts were washed with aq. HCl (1 M) and brine dried (Na2SO4) and concentrated under reduced pressure to give the title compound; compounds 1andash;f decomposed to give aniline and aldehydes if subjected to chromatography on a silica gel column. 2-(N-Methyl-o-bromoanilino)pent-3-enenitrile 1a. Yield 59; oil; TLC EtOAcndash;hexane (2 98) Rf 0.28; nmax(neat)/cm21 2960 2801 2240 (CN) 1590 1476 970 and 760; dH(CDCl3) 1.73 (3 H ddd J 6 1 1 CHCH3) 2.65 (3 H s NCH3) 4.80 (1 H br s NCH) 6.56 (1 H ddq J 15 3 1 3-H) 6.06 (1 H dqd J 15 6 1 4-H) 6.88ndash;6.96 (1 H m ArH) 7.20ndash;7.23 (2 H m ArH) and 7.48 (1 H dd J 8 1.5 ArH); dC(CDCl3) 17.4 (q C-5) 35.0 (q NCH3) 58.3 (d C-2) 115.4 (s CN) 120.3 (s) 123.2 (d) 123.6 (d) 126.1 (d) 128.4 (d) 131.8 (d) 133.7 (d) and 147.9 (s); m/z 266 (M 1 21 28) 264 (M1 32) 185 (68) 157 (100) 105 (52) and 77 (74) (Found M 266.0238.C12H13N2Br requires M 266.0242). 2-(N-Methyl-o-bromoanilino)hept-3-enenitrile 1b. Yield 78; oil; TLC EtOAcndash;hexane (2 98) Rf 0.25; nmax(neat)/cm21 2960 2800 2240 (CN) 1590 1490 970 and 760; dH(CDCl3) 0.90 (3 H t J 7 H-7) 1.35ndash;1.50 (2 H m H-6) 2.08 (2 H dt J 7 7 H-5) 2.72 (3 H s NCH3) 4.89 (1 H br dd J 2 1 NCH) 5.57 (1 H dd J 16 2 3-H) 6.10 (1 H dtd J 16 7 1 4-H) 6.93ndash;7.02 (1 H m ArH) 7.23ndash;7.34 (2 H m ArH) and 7.55 (1 H dd J 8 1 ArH); dC(CDCl3) 13.5 (q C-7) 21.8 (t C-6) 33.9 (t C-4) 35.0 (q NCH3) 58.3 (d C-2) 115.4 (s CN) 120.3 (s) 122.5 (d) 123.2 (d) 126.1 (d) 128.4 (d) 133.6 (d) 136.9 (d) and 147.9 (s); m/z 294 (M 1 21 9) 292 (M1 11) 185 (64) 157 (100) 105 (50) and 77 (76) (Found M 292.0574.C14H17N2Br requires M 292.0575). 4-Methyl-2-(N-methyl-o-bromoanilino)pent-3-enenitrile 1c. Yield 83; oil; TLC EtOAcndash;hexane (2 98) Rf 0.29; nmax(neat)/ cm21 2920 2220 (CN) 1600 1490 770 740 and 670; dH(CDCl3) 1.68 3 H d J 1 1/2 times; C(CH3)2 1.81 3 H d J 1 1/ 2 times; C(CH3)2 2.84 (3 H s NCH3) 4.91 (1 H d J 8 NCH) 5.34 (1 H br d J 8 3-H) 6.95ndash;7.06 (1 H m ArH) 7.26ndash;7.35 (2 H m) ArH and 7.56 (1 H d J 8 ArH); dC(CDCl3) 18.6 (q C-5), J. Chem. Soc. Perkin Trans. 1 1997 2847 25.8 (q C-59) 36.6 (q NCH3) 54.0 (d C-2) 116.0 (s CN) 117.1 (s) 120.7 (s) 123.7 (d) 126.3 (d) 128.3 (d) 133.7 (d) 140.7 (s) and 148.0 (s); m/z 280 (M 1 21 7) 278 (M1 7) 265 (14) 263 (13) 185 (69) 157 (100) and 105 (51) (Found M 27.0421.C13H15N2Br requires M 278.0419). 2-(N-Methyl-o-bromoanilino)-4-phenylpent-3-enenitrile 1d. Yield 86; white solid mp 86ndash;88 8C; TLC EtOAcndash;hexane (2 98) Rf 0.20; nmax(KBr)/cm21 3054 2234 (CN) 1582 1469 968 741 and 695; dH(CDCl3) 2.78 (3 H s NCH3) 5.11 (1 H dd J 4 1 2-H) 6.32 (1 H dd J 16 4 3-H) 6.97ndash;7.08 (2 H m ArH) 7.26ndash;7.30 (5 H m ArH) 7.45 (2 H dd J 8 1 ArH) and 7.59 (1 H d J 8 ArH); dC(CDCl3) 35.4 (q NCH3) 58.6 (d C-2) 115.1 (s CN) 120.4 (s) 121.6 (d) 123.3 (d) 126.3 (d) 126.8 (2 times; d) 128.5 (d) 128.6 (d) 128.7 (2 times; d) 133.7 (d) 134.9 (d) 135.1 (s) and 147.8 (s); m/z 328 (M 1 21 7) 326 (M1 8) 247 (28) 157 (82) 142 (100) 115 (55) and 77 (14) (Found M 326.0420. C17H15N2Br requires M 326.0419). 2-(N-Methyl-o-bromoanilino)hepta-3,5-dienenitrile 1e.Yield 83; white solid mp 65ndash;67 8C; TLC EtOAcndash;hexane (2 98) Rf 0.19; nmax(KBr)/cm21 2955 2811 2230 (CN) 1595 1508 990 and 743; dH(CDCl3) 1.79 (3 H d J 7 CHCH3) 2.73 (3 H s NCH3) 4.98 (1 H d J 4 NCH) 5.66 (1 H dd J 15 4 3-H) 5.87 (1 H dq J 15 7 6-H) 6.12 (1 H dd J 15 10 5-H) 6.59 (1 H dd J 15 10 4-H) 6.97ndash;7.04 (1 H m ArH) 7.29ndash;7.31 (2 H Scheme 4 N Me NPdBr Me R1 R NPdBr N Me N R R2 Nndash; Me PdBr N Me Me N N Me NH R2 R R R2 N N Me HN N Me Me N Me NPdBr R R1 2a-c Pd0 Na2CO3 Na2CO3 H-shift electrocyclization and oxidative aromatization 45 36e R = H R2 = Et 48 R = Me R2 = H 42a R = Me R1 = H 42b R = Pr R1 = H 42c R = R1 = Me 43a 43b R = Pr R1 = H 43c R = R1 = Me 44 46b R2 = Et 46c R2 = H ndash;H+ for 42a 47b R2 = Et 47c R2 = H ndash;Pd0 ndash;Brndash; ndash;Pd0 ndash;Brndash; m ArH) and 7.57 (1 H dd J 8 ArH); dC(CDCl3) 18.1 (q C-7) 35.2 (q NCH3) 58.2 (d C-2) 115.2 (s CN) 120.3 (s) 121.8 (d) 123.2 (d) 126.1 (d) 128.4 (d) 129.4 (d) 132.9 (d) 133.7 (d) 135.2 (d) and 147.9 (s); m/z 292 (M 1 21 26) 290 (M1 29) 277 (21) 275 (20) 211 (51) 185 (74),157 (100) 106 (50) and 77 (60) (Found M 290.0417.C14H15N2Br requires M 290.0419). 2-Cyclopropyl-2-(N-methyl-o-bromoanilino)ethanenitrile 1f. Yield 78; oil; TLC EtOAcndash;hexane (5 95) Rf 0.22; nmax(neat)/ cm21 2960 2210 (CN) 1590 1480 1280 and 760; dH(CDCl3) 0.61ndash;0.83 4 H m CH(CH2)2 1.32ndash;1.43 1 H m CH(CH2)2 2.91 (3 H s NCH3) 4.15 (1 H d J 9 NCH) 6.96ndash;7.04 (1 H m ArH) 7.30 (2 H dd J 8 8 ArH) and 7.56 (1 H dd J 8 ArH); dC(CDCl3) 2.1 (t) 4.1 (t) 11.8 (d C-3) 36.1 (q NCH3) 60.2 (d C-2) 115.4 (s CN) 120.5 (s) 123.6 (d) 126.2 (d) 128.4 (d) 133.6 (d) and 147.9 (s); m/z 266 (M 1 21 68) 264 (M1 72) 240 (18) 238 (20) 225 (82) 223 (92) 186 (70) 184 (83),105 (68) 84 (7) 77 (68) and 49 (100) (Found M 264.0268.C12H13N2Br requires M 264.0262). Preparation of N-methyl-o-bromoanilinoalk-2-enenitriles 2andash;e The appropriate N-methyl-o-bromoanilinoalk-3-enenitrile was treated with ButOK (1.1 equiv.) at 0 8C in a mixture of THF (10 ml) and ButOH (2 ml). After 2 h the reaction was quenched by the addition of aqueous NH4Cl (5 ml) to the mixture which was then extracted with ethyl acetate. The combined extracts were washed with brine dried (Na2SO4) concentrated and purified by chromatography on a silica gel column with gradients of EtOAc and hexane to afford the title compounds. 2-(N-Methyl-o-bromoanilino)pent-2-enenitrile 2a. Yield 64 (this compound was a mixture of two isomers E:Z = 95 5).(2E)-Isomer oil; TLC EtOAcndash;hexane (2 98) Rf 0.23; nmax(neat)/cm21 2890 2205 (CN),1603 1585 1470 750 and 720; dH(CDCl3) 1.07 (3 H t J 6 CH2CH3) 2.36 (2 H dq J 6 6 CHCH2) 3.03 (3 H s NCH3) 5.26 (1 H t J 6 3-H) 7.09 (1 H ddd J 8 8 1 ArH) 7.18 (1 H dd J 8 1 ArH) 7.33 (1 H ddd J 8 8 1 ArH) and 7.60 (1 H dd J 8 1 ArH); dC(CDCl3) 14.4 (q C-5) 22.8 (t C-4) 39.4 (q NCH3) 114.3 (s CN) 121.9 (2 times; s) 123.5 (d) 127.6 (d) 127.7 (d) 128.4 (d) 133.8 (d) and 144.8 (s); m/z 266 (M 1 21 28) 264 (M1 32) 251 (75) 249 (74) 199 (51) 169 (100) 157 (23) and 77 (70) (Found C 54.02; H 4.99; N 10.58; M 266.0238. C12H13N2Br requires C 54.54; H 4.96; N 10.61; M 266.0242); (2Z)-isomer dH(CDCl3) 0.85 (3 H t J 6 CH2CH3) 3.12 (3 H s NCH3) and 5.74 (1 H t J 6 3-H). 2-(N-Methyl-o-bromoanilino)hept-2-enenitrile 2b.Yield 62 (this compound was a mixture of two isomers E:Z = 94 6). (2E)-Isomer oil; TLC EtOAcndash;hexane (2 98) Rf 0.24; nmax(neat)/cm21 2890 2210 (CN) 1605 1590 1470 745 and 720; dH(CDCl3) 0.93 (3 H t J 7 CH2CH3) 1.30ndash;1.46 (4 H m CH2CH2CH3) 2.35 (2 H dt J 7 7 CHCH2) 3.04 (3 H s NCH3) 5.25 (1 H t J 7 3-H) 7.10 (1 H ddd J 8 8 1 ArH) 7.18 (1 H dd J 8 1 ArH) 7.33 (1 H ddd J 8 8 1 ArH) and 7.60 (1 H dd J 8 1 ArH); dC(CDCl3) 13.8 (q C-7) 22.0 (t C- 6) 29.1 (t C-5) 31.9 (t C-4) 39.5 (q NCH3) 114.4 (s CN) 121.9 (s) 122.2 (d) 122.3 (s) 127.6 (d) 127.7 (d) 128.4 (d) 133.9 (d) and 144.9 (s); m/z 294 (M 1 21 11) 292 (M1 11) 204 (100) 187 (59) 185 (61) 148 (18) and 77 (20) (Found C 57.13; H 5.89; N 9.57; M 292.0570. C14H17N2Br requires C 57.52; H 5.87; N 9.59; M 292.0575); (2Z)-isomer dH(CDCl3) 3.11 (3 H s NCH3) and 5.79 (1 H t J 7 3-H).4-Methyl-2-(N-methyl-o-bromoanilino)pent-2-enenitrile 2c. Yield 71 (this compound was a mixture of two isomers E:Z = 91 9). (2E)-Isomer oil; TLC EtOAcndash;hexane (2 98) Rf 0.24; nmax(neat)/cm21 2960 2220 (CN) 1600 1500 1470 760 750 and 730; dH(CDCl3) 1.08 6 H d J 7 CH(CH3)2 2.72ndash;2.91 1 H m CH(CH3)2 3.03 (3 H s NCH3) 5.08 (1 H d J 10 3- H) 7.05ndash;7.20 (2 H m ArH) 7.26ndash;7.37 (1 H m ArH) and 7.60 (1 H dd J 8 1 ArH); dC(CDCl3) 23.3 2 times; q CH(CH3)2 29.6 (d C-4) 39.5 (q NCH3) 114.4 (s CN) 120.6 (s) 121.8 (s) 127.5 (d) 127.6 (d) 128.4 (d) 129.5 (d) 133.9 (d) and 144.9 (s); 2848 J. Chem. Soc. Perkin Trans. 1 1997 m/z 280 (M 1 21 20) 278 (M1 22) 265 (72) 263 (74) 199 (62) 169 (100) and 77 (24) (Found C 55.98; H 5.42; N 10.06; M 278.0421.C13H15N2Br requires C 56.11; H 5.44; N 10.09; M 278.0419); (2Z)-isomer dH(CDCl3) 3.10 (3 H s NCH3) and 5.52 (1 H t J 7 3-H). 2-(N-Methyl-o-bromoanilino)-4-phenylpent-2-enenitrile 2d. Yield 67 (this compound was a mixture of two isomers E:Z = 93 7). (2E)-Isomer oil; TLC EtOAcndash;hexane (2 98) Rf 0.17; nmax(neat)/cm21 3020 2220 (CN) 1610 1496 1020 and 690; dH(CDCl3) 3.04 (3 H s NCH3) 3.68 (2 H d J 8 PhCH2) 5.34 (1 H t J 8 3-H) 7.10 (1 H ddd J 8 8 1 ArH) 7.18ndash;7.34 (7 H m ArH) and 7.59 (1 H dd J 8 1 ArH); dC(CDCl3) 32.4 (t PhCH2) 39.4 (q NCH3) 114.2 (s CN) 119.2 (d) 119.7 (s) 122.0 (s) 126.5 (d) 127.7 (d) 127.9 (3 C d) 128.4 (2 C d) 133.8 (2 C d) 137.6 (s) and 144.7 (s); m/z 328 (M 1 21 38) 326 (M1 35) 247 (100) 169 (60) 155 (42) 91 (68) and 77 (30) (Found M 326.0410.C17H15N2Br requires M 326.0419); (2Z)-isomer dH(CDCl3) 3.16 (3 H s NCH3) and 5.92 (1 H t J 7 3-H). 2-(N-Methyl-o-bromoanilino)hepta-2,4-dienenitrile 2e. Yield 65 (this compound was a mixture of two isomers 2E:2Z = 90 10). (2E)-Isomer oil; TLC EtOAcndash;hexane (2 98) Rf 0.26; nmax(neat)/cm21 2960 2221 (CN) 1575 1476 962 764 and 725; dH(CDCl3) 1.02 (3 H t J 7.5 CH2CH3) 2.16 (2 H qdd J 7.5 7.5 1 CH2CH3) 3.11 (3 H s NCH3) 5.80 (1 H dq J 16 7.5 5- H) 5.82 (1 H d J 10 3-H) 6.38 (1 H ddq J 16 10 1 4-H) 7.12 (1 H ddd J 8 8 1 ArH) 7.20 (1 H dd J 8 1) 7.34 (1 H ddd J 8 8 1 ArH) and 7.62 (1 H dd J 8 1 ArH); dC(CDCl3) 13.5 (q CH2CH3) 26.0 (t CH2CH3) 39.6 (q NCH3) 114.4 (s CN) 119.8 (d) 120.1 (s) 122.5 (s) 125.1 (d) 128.3 (d) 128.6 (2 times; d) 134.0 (d) 137.7 (d) and 144.5 (s); m/z 292 (M 1 21 31) 290 (M1 29) 211 (100) 182 (59) and 169 (21) (Found C 57.82; H 5.23; N 9.64; M 290.0439.C14H15N2Br requires C 57.92; H 5.21; N 9.66; M 290.0419); (2Z,4E)-isomer dH(CDCl3) 3.15 (3 H s NCH3) and 6.18 (1 H dd J 9 1 3-H). Preparation of 2-alkenylamino-3-(o-bromophenyl)propanenitriles 7andash;c and 8andash;c Under an atmosphere of argon a solution of diisopropylamine (0.9 ml 5.5 mmol) in THF (10 ml) was cooled to 215 8C and a solution of BuLi (1.