Alkynes, cyclization anilines

Amines undergo aminopalladation to alkynes. The intramolecular addition of amines to alkynes yields cyclic imines. The 3-alkynylamine 273 was cyclized to the 1-pyrroline 274, and the 5-alkynylamine 275 was converted into the 2,3,4,5-tetrahydropyridine 276[137]. Cyclization of o-(l-hexynyl)aniline (277)... 

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. 

This approach is important for the synthesis of cinnolines. CHEC(1984) <1984CHEC(2)1> already covered several examples. The methodology used starts with an aniline ortho substituted with an alkene (Widman-Stoermer type), alkyne (Richter type), or enolisable ketone (Borsche type) which is diazotisized, delivering the sixth atom, allowing cyclization. CHEC-II(1996) <1996CHEC-II(6)1> gave more examples. 

Later, Arcadi showed that /J-keto-imines react with alkynes intramolecularly to give pyrroles. The intermolecular animation with aniliaes was later developed by Hayashi and Tanaka using a cationic Au(I) catalyst to form imines (equation 27). More recently, Arcadi etal. developed an intramolecular version for the cyclization of o-alkynylanilines to form indoles (equation 28) and Li reported a double intra- and intermolecular hydroamination to obtain A-vinylindoles. " O-Substituted hydroxylamines can also undergo this type of transformation to dihydroisoxazole derivatives. " " Tandem sequences that involve a first alkyne-hydroamination step with anilines have been recently developed " " and are similar to the previonsly discnssed additions with phenols that access isoflavone skeletons. 

Aryl radicals participate in radical cyclization reactions when the aromatic ring has an alkene or alkyne substituent. o-Iodo aryl allyl ethers cyclize to benzofuran derivatives, for example, when treated with AIBN, aqueous H3PO2 and NaHCOs in ethanol. Cyclization of an o-bromo-A-acyl aniline (a methacrylic acid derivative) with AIBN/BusSnH gave an indolone under the typical conditions used for cyclization of alkenes. 

A novel one-pot domino process was developed to synthesize substituted 1,2-dihydroquinoline derivatives 102 with high regioselectivity using a silver catalyst <05OL2675>. Scheme 29 shows the proposed pathway, which starts with the hydroamination of alkyne 103 and aniline 104. This is followed by C-H addition with another alkyne 103 and C-H addition cyclization to give intermediate 105. The final step is another C-H addition with alkyne 103 yielding the desired product 102. The scope and mechanism of this one-pot process is still under investigation. 

Similarly, the aniline-derived imine 679 bearing an appropriately placed alkyne, underwent the CuCl-mediated cyclization with capture of methanol to give indoles 680 in moderate (53%) to good (74%) yields (04TL35). Several alcohols also participated in the reaction, including phenol, as did aryl alkynes. 

Aniline, acetanilide, benzyl alcohol or methyl benzoate containing a halogen atom in the or /zo-position react with 1 -alkynes in the presence of bis(triphenylphosphine)palladium(II) chloride and copper(I) iodide to give the corresponding o-alkynylbenzenes (e.g. equation 6). Some of the products can be cyclized the aniline derivative 53, for instance, is converted into 2-phenylindole in 99% yield on treatment with a catalytic amount of copper(I) iodide. ... 

Synthesis of Heterocycles via Addition to Alkenes and Alkynes. The regioselective synthesis of heterocycles has been demonstrated using both cyclohexenyl phenols and anilines in which the products differ in both cases by either a 5-exo-trig or 6-endo-trig cyclization. For the phenolic substrate, the 6-endo cyclization product was formed exclusively, while under almost identical conditions, the aniline gave only the 5-exo cyclization (eqs 28 and 29). Similarly, hydroxycoumarin derivatives also cyclize in a 6-endo fashion similar to the cyclohexenylphenols. ... 

Mono-substituted anilines bearing an internal alkyne can be cyclized to quinolines either by metal-mediated hydroarylation of alkynes or through an eleetrophile-mediated Friedel-Craft type reaction. ... 

Several metals have been reported of being able to hydroaiylate alkynes as in the examples shown below. Thus, di-substituted-propargyl anilines can be cyclized either in the presence of copper(I) chloride at reflux or by a mixture of palladium acetate and trifluoroacetic acid. ... 

SFs-anilines, aldehydes, and arylacetylenes (15EJ01415). This method was inspired by the Fe(III)-catalyzed aerobically oxidative synthesis of quinoHnes developed by Tu and coworkers (09CEJ6332). Both 3- and 4-SF5-anihnes (39 and 11), various aldehydes—aromatic, heterocyclic, formaldehyde, trifluoroacetaldehyde ethyl glyoxylate, and aromatic alkynes can serve as reaction components to provide access to a series of 2-aryl substituted 6(7)-SF5-quinolines 104a—s (Scheme 26). Flowever, cyclization products were not observed when aliphatic alkynes were used under the reported conditions. 

Alkynes have been widely employed as the rr-component, with both A -nucleophiles (Scheme 6.46)" and 0-nucleophiles (Scheme 6.47) to give a variety of heterocycles. An application of particular importance has been in the synthesis of indoles 6.142 by the cyclization of o-alkynyl aniline 6.141 derivatives (Scheme 6.48)." The system may be extended to the synthesis of 3-acyl indoles 6.144 by the inclusion... 

The FGI s e/flead to the dihydroquinoUnes 61 and 62. For 62, a synthesis involving a cyclizing addition (situation 60) of alkynes to N-phenylimines is retroanalytically relevant Further retroanalysis of 61 and 62 (operations h and i) suggests intermediates which, after disconnection at the C-4/benzene ring (j and k), allow an SeAr cydization realizable via aniline derivatives 63 and 64 with an electrophilic center (C-X, C=0) in the y-position to nitrogen. 

Indoles are also accessed by intramolecular cyclization of azides, -acyl, or JV-tosyl anilines with alkynes (eqs 25-28). 

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