Unusual Cyclizations

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

An unusual cyclization, which results in carbocycles rather than heterocycles, was described in (69JCS2453). The reaction between o-iodobenzamides and copper phenylacetylides in pyridine leads to indanone (74%) rather than tolane (Scheme 124). 

The structure of this compound is confirmed by the preparation of the 1-acetyl derivative, acid degradation to 4-methylquinoxalin-3-one-2-carboxylic acid (12), and alternative synthesis from the acid chloride of (12) and AW -dimethyluread A most unusual cyclization occurs when AW-dimethyl-o-phenylenediamine (15) is treated with alloxan in ethanolic solution this apparently involves an A-methyl group and leads to the formation of the spirobarbituric acid (16). The struc-... 

Probably the most straightforward approach is constituted by protonation of the Ti - C bond. This was first realized by using collidine hydrochloride as the acid (Scheme 12). These conditions have proven especially useful in unusual cyclizations as discussed later [66,67]. 

The following unusual cyclization took place by the reaction of p-benzoquinone coordinated by palladium with two moles of butadiene at 60°C to give the tricyclic compound, 128 (117). 

The Mediterranean has also given peculiar triterpenes of squalene origin and an unusual cyclized cembranoid, coralloidolide C (Chart 7.5.A/I/PO). The latter resembles diterpenoids from tropical octocorals, indicating that these cnidarians, on migration to temperate waters, have conserved genes for secondary metabolites. 

The highly strained double bond in methylenecyclopropane displays enhanced reactivity in cycloaddition reactions. In addition to normal [4+2] cycloaddition to 1,3-dienes (e.g. equation 13)32, methylenecyclopropane and its derivatives have a pronounced tendency to undergo thermal [2+2] cycloaddition reactions. For example, thermal dimerization of methylenecyclopropane in the gas phase results in formation of isomeric dispirooctanes 16 and 17 (equation 14)33. This unusual cyclization is considered to proceed via a stepwise radical mechanism involving the intermediacy of biradical 18 (equation 15)34. Equation 15 demonstrates that methylenecyclopropanes possessing substituents capable of stabilizing intermediate radicals undergo efficient [2+2] dimerization even... 

Allenes insert into ir-allyl complexes so as to generate new ir-allyl species (equation 78).248 The insertion of 2-r-butyl-1,3-butadiene into ir-allylpalladium complexes proceeds normally, but is then followed by an unusual cyclization reaction, presumably due to the disposition of the butenyl frag-... 

The C(2)-C(3) bond formation provides the basis for the construction of t h i e n o [ 3,2 - A ] pyrid i nes according to method N. Scarce examples were, as a rule, based on nontrivial synthetic approaches. For example, thienopyridazines 164 undergo an unusual cyclization to give pyridothienopyridazines 165 under the conditions of the Vilsmeier-Haack reaction (2001T5413). 

Since simple aliphatic aldehydes readily undergo aldol condensation under basic conditions, their intermolecular a-arylation is not successful. However, the intramolecular reaction is possible (Eq. 20) [59]. It is interesting that an unusual cyclization product via cleavage of the aldehyde C-H bond is observed in addition to the normal a-arylation product. Other examples of this kind of arylation are described in Sect. 3.3. 

A number of intramolecular coupling reactions that involve reductive cyclization of a (cyclohexadiene)Fe(CO)3 complex that bears a pendant alkene or diene have been reported. Under CO atmosphere, this unusual cyclization presumably produces an intermediate r] -7t-d y complex that then rearranges via hydride migration. In the case of the pendant diene, a second such process can occur (Scheme 68). 

Srikrishna A (2001) Unusual cyclizations. In Renaud P, Sibi M (eds) Radicals in organic synthesis, vol 2. Wiley, Weinheim, p 151... 

When the related aziridine 195 was used containing one less carbon in the tether, an unusual cyclization occurred which corresponds to a formal [3+2] aziridine allylsilane cycloaddition to give the bicyclic pyrrolidine 196. This substrate was used for the preparation of other fused ring systems (Scheme 53) <1999T8025>. 

Unusual cyclizations onto epoxides can take place through presumed ruthenium ketene intermediates. Two examples are shown here (Equations 59 and 60)<2004JOC7700, 2004JA6895, 20050L1745>. 

The attempted conversion of the aldehyde in compound (65) to a methyl group by reduction of the tosylhydrazone with NaBH4 (ethanol solvent) led instead to the furan derivative (66), resulting from an unusual cyclization with elimination of a MeOCH2 group. 

An unusual cyclization reaction, involving an interesting rearrangement, has been used to prepare a triazine derivative [1791] ... 

In an unusual cyclization process, benzil monohydrazones heated in toluene form 4,5-diphenyl-imidazoles (>80%) rather than the expected pyrazoles. The way in which the N—N bond breaks and reorganizes is uncertain, but either a diaziridine or a diazetidine ylide intermediate may be involved. If it is the latter the 1,2-bond of imidazole is formed if the former it will be 1,5-bond formation <85TL1595,86BSB655>. Similarly, cyclization of phenacylethyleneketal hydrazones of benzaldehyde and ethanal yields both pyrazoles and imidazoles (Equation (62)) <86BSB1073>. 

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