Propenyl indole

A 20% excess of ethylmagnesium bromide was prepared from magnesium (6.5 g) in ether (80 ml) by adding ethyl bromide (30 g) in ether (30 ml). Indole (25.8 g) in benzene (50 ml) was then added slowly with stirring and stirring was continued for 20 min after addition was complete. A solution of allyl bromide (29.2 g) in benzene (20 ml) was then added slowly. The mixture was stirred overnight and then diluted with ether and the product isolated and purified by distillation (22.7 g, 70% yield). 

A solution of benzyl indole-5-carboxylate(1.0g, 3.98 mmol) and methyl 4-(bro-momethyl)-3-methoxybenzoate (2.06 g, 7.97 mmol) in dry DMF (10 ml) was heated at 80°C for 24 h. The reaction solution was cooled, poured into water (100 ml) and the product extracted with EtOAc (3 x 75 ml). The extract was washed with water and brine and dried over MgSO, . The product was obtained by evaporation of the solvent and purified by chromatography on silica gel using 1 4 EtOAc/hexane for elution. The yield was 1.11 g (32%) and some of the indole (30%) was recovered unreacted. 

Printed with FinePrint 2000 - register at http/Mwwfineprint C( 

Casnati, M. Franeioni, A. Guareschi and A. Pochini, Tetrahedron Lett. 2485 (1969), 

Kawaguchi, Y. Enoki and T. Oishi, Chem. Pharm. Bull. 38, 323 (1990), 

---

Methyl-5-phenyl-1 //-pyrrole, M-60115 3-(2-Propenyl)indole, P-60183 1,2,3,4-Tetrahydrocyclopent[Z)]indole, T-70049... 

As illustrated in the conversion of 111 to 112 below, a variety of indoles bearing chirality at C3 was accessed by O Shea and co-workers by means of a (-)-sparteine directed enantioselective carbolithiation of 2-propenyl anilines, followed by electrophilic trapping-cyclization of the lithio intermediates <06JACS10360>. 

TV-Acyl indoles derived from amides have been employed for the conversion of lactones into protected hydroxyacids. Thus, (chloromethyl)alumi-num 2-(2-propenyl)anilide reacts (120) with 1,4- and 1,5-lactones, as for example per-O-terZ-butyldimethylsilyl-D-ribono-1,4-lactone (104), to afford hydroxyamides. After protection of the free hydroxyl group, these amides were converted by ozonolysis into TV-acyl indoles, 105, which were readily saponified to the acid 106. 

Ene reaction or dimerization competed with the Diels-Alder cycloaddition when 3-(2-propenyl) Af-substituted indoles 136 were employed as diene systems toward NPMI (88HCA467). On the other hand, with /3-substituted 3-vinyl-l//-indoles 137 and the same dienophile, the products include carbazole derivatives and Michael adducts (Scheme 5) (87HCA1419). 

Chemical Name lH-Indole-3-acetic acid, 5-methoxy-2-methyl-l-(l-oxo-3-phenyl-2-propenyl)-... 

Benzoxazol 2-(l,l-Dimethy]-2-propenyl)- E8a, 1150 [Cl -> C(CH3)2-CH=CH2] lH-Carbazol 4a-Hydroxy-2,3,4,4a-tetrahydro- IV/lc, 483 Cyclobutan 1-Benzyl-l-cyan-3-hydroxy- E17e, 67 [(2-CN-ethyl) — oxiran + R —MgX] Cyclopentan-(spiro-2)-2,3-dihydro-indol - -3-oxo- VII/2a, 1051 Cyclopropan 2-Cyan-l-methoxy-2-methyl-l-phenyl- E17a, 764 (RO — CAr = Cr + En)... 

DICHLORO-3-((1 E)-3-OXO-3-(PHEN YLAMINO)-1 -PROPENYL)-1 H-INDOLE-2-CARBOXYLIC ACID,... 

Dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarb-oxylic xid 1,3,4,5,6,7-hexa-hydro-1,3-dioxo-2H-iso-indol-2-yl)methyl ester. AI3-27339 Bioneopynamin Caswell No. 844 CCRIS 3284 (1-Cyclohexane-1,2-dicarboximido)methyl chrys-anthemumate Cyclohex-1-ene-1,2-dicarboximidomethyl ( )-cis-trans-... 

Heckman and Best (1587) reported the identification of nearly 270 previously unidentified and confirmation of over 150 previously identified A-containing components in CSC. These included several components structurally similar to some of the A-heterocycfic amines 9H-pyrido[2,3- ]indole, 2-methyl-97/-pyrido[2,3- ]indole, 2-(2-methylpropyl)-9H-pyrido[2,3-fc] indole, 2-pentyl-9H-pyrido[2,3-fc]indole, l-butyl-97/-pyrido [3,4- ]indole, l-propenyl-9H-pyrido[3,4- ]indole, and a partially characterized norharman. 

Bennasar also recently extended their interest in the cyclization of A -alkenyl substituted 2-indolylacyl radicals towards the annulation of larger rings [126]. A 7-endo-mg closure was observed when brotnovinyl substituted seleno ester 237 was treated with excess tin hydride in EtaB. In addition to the desired azepino[3,2-I>] indole 238, the 6-exo cyclization product 239 was observed as the minor product, with both products showing no evidence of the bromine atom in their strucmres. Previous attempts at this cyclization using a tethered allyl moiety, rather than the 2-bromo-2-propenyl tether, also gave the azepinoindole but only as the minor product. 

In 2007, Chan and eo-workers reported the synthesis of a new class of chiral ferrocenyl heterobidentate P/S ligands, which are readily available from Ugi s amine, and they reported their applieation in Pd-catalyzed asymmetric allylic alkylation of l,3-diphenyl-2-propenyl acetate with indoles. The corresponding C3 alkylated indoles derivatives were produced in good yields with up to 96% ee (Scheme 6.78). 

Franzen and coworkers described a series of indole-phos-phine-oxazoline (IndPHOX) ligands, 231-238 (Scheme 35). The power of these ligands is demonstrated by the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphe-nyl-2-propenyl acetate with dimethyl malonate with 98%... 

Many metal-catalysed allylic substitution reactions have been reported. Adding a terminal olefin to the binaphthyl backbone of a phosphorus amidite ligand in a [PdCl(C3H5)]2-ligand-K2C03 catalysed reaction between indoles and l,3-diphenyl-2-propenyl acetate has enabled the allylic substitution to occur, with yields ranging from 72 to 96%, with 91-98% ee. 

Other Names 3//-Indolium, 2-[3-(l,3-dihydro-3,3-dimethyl- 1 -octadecyl-2//-indol-2-ylidene)-1 -propenyl]-3,3-dimethyl-l-octadecyl, perchlorate l,l -Dioctadecyl-3,3,3, 3 -tetramethylindocarbocyanine perchlorate D 282 D 282 (dye) Dil Dil (dye) DilC18(3)... 

---