Cyclization onto aromatic rings

Imidoylnitrenes are aza analogs of both vinylnitrenes and acylnitrenes. Not unexpectedly, therefore, the two major reactions are cyclization onto aromatic rings, forming benzimidazoles, and a Wolff-type rearrangement to carbodiimides. 1,5-Diphenyltetrazole (118) forms a mixture of 2-phenylbenzimidazole (119) (23%) and diphenylcarbodiimide (120) (76%) on thermolysis above 200°C.173,174 However, only the benzimidazole was formed by photolysis.175... 

In summary, intramolecular radical cyclization reactions onto aromatic rings can provide quick access of otherwise not so easily assembled Ca0. -C.ryi bonds, although the yields are generally low and the process suffers from a lack of regioselectivity. Noticeably, Crich found that a catalytic amount of benzeneselenol, which can also be generated in situ reduction of diphenylselenide with stannane [57]. This method should find synthetic utility in intramolecular radical addition to arenes. 

The Graebe-Ullmann synthesis of carbazoles by gas-phase pyrolysis80-83 or photolysis69 of l-aryl-l,2,3-benzotriazoles involves the cyclization of imidoylcarbenes (or the mesomeric 1,3-diradicals) onto aromatic rings (Eq. 24). This cyclization is apparently very rapid, for the use of substituted... 

The TT-cyclization of A/ -acyliminium ions onto aromatic rings is a useful method for the preparation of isoquinolines fused with heterocycles. Heating azide 102 with one of the compounds methyl (5)-mandelate (103) or methyl (i )-mandelate (63) in toluene provides the carbamates 104 and 105 respectively. DIBAL reduction of 104 or 105 with DIBAL in toluene... 

Semmelhack, M. F. and Bargar, T. M., Cyclizations of enolates onto aromatic rings via the photo-SrjjI reaction preparative and mechanistic aspects,/. Org. Chem., 42, 1481, 1977. 

In 2003, Togo and co-workers described a radical cyclization and ionic cyclization onto the aromatic rings of 2-(aryl)ethanesulfonamides 21 to produce 3,4-dihydro-2,l-benzothiazine 2,2-dioxides with polymer-supported hypervalent iodine reagents in good yields <03ARK11>. 

Further variations of the general scenario described in Scheme 4 consist in trapping adduct radical 48 before oxidation occurs7. This can be achieved if intramolecular radical additions are possible, as is the case in radical 62. Oxidation of 62 to the corresponding allyl cation is slower than 6-ew-cyclization to the chlorobenzene ring to form radical 63, which subsequently is oxidized to yield tetrahydronaphthalene 64 as the main product (equation 27). This sequence does not work well for other dienes such as 2,3-dimethyl-1,3-butadiene, for which oxidation of the intermediate allyl radical is too rapid to allow radical cyclization onto the aromatic TT-system. 

With a low concentration of thiol, propargyl aryl ethers or amines show vicinal bis(stannation), and it is suggested that this results from stabilization of the initial radical by cyclization onto the aromatic ring (Equation (17)). 

Scheme 19. Radical cyclization onto an aromatic ring...

A new and related carboannulation reaction is possible, that involves insertion of alkynes to aryl or alkenyl palladium intermediates, and subsequent cyclization onto an aromatic ring already present in the substrate [252], The cyclization of the enol triflate 509 to give 510 is an example. The reaction was applied to the synthesis of the indolocarbazole derivative 512 from the iodobisindole 511 [253],... 

Chloride ion in benzyl(triethyl)ammonium chloride can activate a nitrile group in dicyanomethylenedithiazole 42 which then cyclizes onto S-l to form the aromatic isothiazole ring and a new cyano group (Equation 17) <1997J(P1)3345>. The yield of isothiazole 86 is quantitative. 

Very few reports describe the use of radical methods in the construction of large ring heterocycles (>7). A peroxydicarbonate-mediated hydrogen atom abstraction from an aldimine followed by cyclization onto an aromatic ring has been applied to the synthesis of dibenzoxazepines 237 [95T12143]. The yield of the heterocyclic product is low. 

We used this method as the key sequence in the synthesis of ( )-lycopodine (78). The intramolecular isomiinchnone cycloadduct 81 was envisaged as the precursor of the key Stork intermediate 79 (via 80) [42]. The heart of our synthetic plan was the formation of the latter intermediate by a Pictet-Spengler cyclization of the N-acyliminium ion derived from 81. Central to this strategy was the expectation that the bicyclic iminium ion originating from 81 would exist in a chair-like conformation [42,43]. Cyclization of the aromatic ring onto the iminium ion center should take place readily from the axial position. The readily available heptenoic acid 82 would serve as the precursor for the a-dia-zoimide, the direct progenitor of the isomiinchnone dipole. This extension of the tandem cycloaddition-cationic 1-cyclization protocol to the formal synthesis of ( )-lycopodine (78) is outlined below. 

Although coupling of aryl diazonium salts at the -position of dienamines yields indazoles on acid-catalysed cyclization, the presence of an electron-donor substituent may render the aromatic ring sufficiently nucleophilic to cyclize onto the iminium group to give cinnolines or 6,7-diazasteroids2,67 (Scheme 40). 

Kariv-Miller and coworkers have developed indirect electroreductive cyclizations with the dimethyl-pyrrolidinium ion (DMP") as a mediator. Preparative electrolysis of 6-hepten-2-one (9) at a graphite cathode afforded cu-dimethylcyclopentanol (10) in 90% yield (equation 5). The reduction is believed to occur via the ketyl radical anion, which cyclizes onto the alkenic bond. In the absence of DMP simple reduction to 6-hepten-2-ol takes place.Very recently it was shown that instead of DMP several aromatic hydrocarbons can be used as mediators to initiate the cyclization reaction. The carbonyl group can also be cyclized onto an alkynic bond and even an aromatic ring. - ... 

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