Alkenes, cyclization anilines

Unlike the intermolecular reaction, the intramolecular aminopalladation proceeds more easily[13,14,166], Methylindole (164) is obtained by the intramolecular exo amination of 2-allylaniline (163). If there is another olefinic bond in the same molecule, the aminopalladation product 165 undergoes intramolecular alkene insertion to give the tricyclic compound 166[178]. 2,2-Dimethyl-l,2-dihydroquinoline (168) is obtained by endo cyclization of 2-(3,3-dimethyiallyl)aniline (167). The oxidative amination proceeds smoothly... 

Meerwein reactions can conveniently be used for syntheses of intermediates which can be cyclized to heterocyclic compounds, if an appropriate heteroatom substituent is present in the 2-position of the aniline derivative used for diazotization. For instance, Raucher and Koolpe (1983) described an elegant method for the synthesis of a variety of substituted indoles via the Meerwein arylation of vinyl acetate, vinyl bromide, or 2-acetoxy-l-alkenes with arenediazonium salts derived from 2-nitroani-line (Scheme 10-46). In the Meerwein reaction one obtains a mixture of the usual arylation/HCl-addition product (10.9) and the carbonyl compound 10.10, i. e., the product of hydrolysis of 10.9. For the subsequent reductive cyclization to the indole (10.11) the mixture of 10.9 and 10.10 can be treated with any of a variety of reducing agents, preferably Fe/HOAc. 

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. 

Heterocycles can be prepared from selenium-induced cyclizations of urethanes, thioesters and alkenes. These cyclizations are seen infrequently, but have much potential in heterocyclic synthesis. The aniline (37) was treated with benzeneselenenyl chloride and silica gel (to facilitate the ring closure) to produce the hexahydrocarbazole (38) in good yield (equation 30). Sulto heterocycles are prepared similarly to nitrogen heterocycles. ... 

The biomimetic construction of piperidine skeletons from N-methylhomoallyl-amines is performed by means of the ruthenium-catalyzed oxidation and subsequent olefm-iminium ion cyclization reaction. trans-l-Phenyl-3-propyl-4-chloropiper-idine 57 ivas obtained from N-methyl-N-(3-heptenyl)aniline stereoselectively via 56 upon treatment ivith a 2 N HCI solution (Eq. 3.72). This cyclization is the first demonstration of biomimetic formation of piperidine structure using N-methyl group, and can be rationalized by assuming the formation of iminium ion 58 by protonation of the oxidation product 56, subsequent elimination of f-BuOOH, nucleophilic attack of an alkene, giving a carbonium ion, which is trapped with Cl nucleophile from the less hindered side. 

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. 

Aniline that is orf/io-substituted with a hexa-2,5-dienyl side-chain undergoes catalytic, palladium-assisted cyclization to 2-propylquinoline (Scheme 34) this is only one of a series of ring-closure reactions involving palladium-promoted nucleophilic attack on an alkene. A tetrahydroquinoline (55) is produced by the action of trifluoroacetic acid on the hydroxylamine (54). This method has also been used to prepare l,4-benzoxazines. ... 

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. ... 

The synthesis of indoles and benzofiirans by the palladium-catalysed cyclization of o-alkynyl anilines and phenols can also form part of tandem processes through interception of the -intermediate (Scheme 6.41). Inclusion of an alkene results in a Heck process, giving 3-vinylated indoles 6.129." As the 3-hydride elimination step causes reduction of the palladium(II) to palladium(O), an oxidizing agent, such as copper(n) must be included to maintain catalysis. The intermediate may also be intercepted by alkoxycarbonylation, giving an ester 6.130." Again an oxidant is needed. 

In this reaction, the tethered alkene functionality of the aniline derivatives form a Tr-allyl complex with the Pd(II) catalyst, and then the cyclization takes place via intramolecular nucleophilic attack by the N to form another Pd-complex, which reacts with CO as the electrophilic carbon source in the presence of MeOH to afford substituted bicy-clic pyrrolidine derivatives. However, these products were not stereoselective in nature. A similar type of Pd-catalyzed nonstereoselective cyclizations were also reported by Weinreb et al. and by Larock and Yang for the construction of bicyclic and bridged aza-cycles." ... 

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