3-Alkylidene-377-indoles

An intramolecular tpio-Friedel-Crafts-type addition of phenols to 3-alkylidene indole-nium cations and formation of iminium cations through rearomatization of the spirocy-clohexadienone units followed by an intramolecular Pictet-Spengler reaction has been reported to give tricyclic indoles (Scheme 166). ... 

Ungesattigte Lactame werden durch Diboran hydroboriert. In 2-Oxo-3-alkyliden-2,3-dihydro-indol-Derivaten ist die C=C-Doppelbindung stark elektrophil, so daB sie mit Natriumboranat selektiv gesattigt werden kann1 ... 

Feldman reported a route to dihydropyrroles, pyrroles, and indoles via the reaction of sulfonamide anions with alkynyliodonium triflates <96JOC5440>. Thus, upon nucleophilic addition of the anion of 91 to the p-carbon of the alkynyliodonium salt, the alkylidene carbene 92 is generated which can the undergo C-H insertion to the desired product 93. 

Pseudo-C3-symmetrical trisoxazoline copper(II) complexes prove to be excellent catalysts in the Friedel-Crafts alkylation of indoles with alkylidene malonates (Eq. 7.13). Water tolerance of chiral catalyst trisoxazoline/Cu(OTf)2 was examined, and it was found that the addition of up to 200 equivalents of water relative to the catalyst in /,vo-butyl... 

The second method leads to the formation 3-alkyl- and 3-arylindoles from the reaction of indole with aldehydes in the presence of alkali metal tetra-carbonylhydridoferrate (Scheme 40).67 It is possible that this novel process may occur via reduction of intermediate 3-alkylidene- or 3-arylidene indolenines. 

Cyclization of 2-(l-alkynyl)XV-alkylidene anilines is catalyzed by palladium to give indoles (Equation (114)).471 Two mechanisms are proposed the regioselective insersion of an H-Pd-OAc species to the alkyne moiety (formation of a vinylpalladium species) followed by (i) carbopalladation of the imine moiety and /3-hydride elimination or (ii) oxidative addition to the imino C-H bond and reductive coupling. 

The palladium catalysed annulation of / -iodoamines and acetylene derivatives has been widely used in the construction of pyrroles and indole derivatives. The strategy, first reported by Larock, is efficient in converting both cyclic and open chain 2-iodo-allylamine derivatives to 3-alkylidene-... 

The catalytic enantioselective addition of aromatic C - H bonds to alkenes would provide a simple and attractive method for the formation of optically active aryl substituted compounds from easily available starting materials. The first catalytic, highly enantioselective Michael addition of indoles was reported by Jorgensen and coworkers. The reactions used a,fl-unsaturated a-ketoesters and alkylidene malonates as Michael acceptors catalyzed by the chiral bisoxazoline (BOX)-metal(II) complexes as described in Scheme 27 [98,99]. 

The enantioselective reactions of indoles using alkylidene malonates gave the alkylation products 92 in excellent yield and with moderate ee. 

Several pseudo-C3-symmetric homo- and hetero-trisoxazolines have been developed and applied successfully in the asymmetric Michael-type alkylation of indoles with alkylidene malonates. The C3-symmetric trisoxazoline 121a-copper(C104)2 -6H20 complex, as a catalyst, is an air- and water-stable compound (Scheme 34) [108-110]. 

The three-component reaction of indole (2) with sugar hydroxyaldehyde 281 and Meldrum s acid 282, with a catalytic amount of D,L-proline, afforded the 3-substitution product 283 as a single isomer [203]. The substituent possesses the czs-fused furo [ 3,2- b ] pyranonc skeleton. The proline catalyzes the Knoevenagel condensation of the sugar aldehyde 281 and Meldrum s acid 282 to provide the alkylidene derivative 284 of Meldrum s acid. Then a diastereo-selective Michael addition of indole and an intramolecular cyclization of this adduct 285 with evolution of carbon dioxide and elimination of acetone furnish the furopyranone in one-pot (Scheme 62). 

Base-induced (KH or /-BuOK) cyclizations of o-alkynylanilines were utilized to prepare 2-substituted indoles and poly-substituted indoles. For example, treatment of alkynes 86 with KH gave the corresponding indoles 87 <03T1571>. Similar base-mediated cyclizations and related indole syntheses were utilized to prepare indole inhibitors of 5 -inosine monophosphate dehydrogenase <03BMCL1273>. Moreover, base-induced cyclizations of arylacetonitriles with oxalic acid bis(imidoyl)chlorides provide a route to 2-alkylidene-3-iminoindoles <03CEJ3951>. 

MALME-3M and the the human breast cancer cell lines pT-49 and T-470. The 3-alkylidene-3H-indole-l-oxide moiety of 14 was successfully synthesized by a cross coupling-reductive condensation sequence. And its total synthesis was accomplished by 17 reaction steps with 4.2% yield. 

Larock has described the reaction of diphenylacetylene with iodosulfonamides 260 to give alkylidene dihydropyrroles 261 [159]. This ring-forming reaction is similar to the large number of related indole syntheses we will see in the next chapter. For example, 262 affords 263 under these conditions. 

Indoles react with aldehydes and ketones under acid catalysis - with simple carbonyl compounds, the initial products, indol-3-yl-carbinols are never isolated, for in the acidic conditions they dehydrate to 3-alkylidene-37f-indolium cations those from aromatic aldehydes have been isolated in some cases reaction of... 

Alkylidene-3/f-indolium cations are themselves electrophiles and can react with more of the indole, as illustrated for reaction with formaldehyde. ... 

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