Fluorene, cyclization

Dication 72 is estimated to have a fluorene cyclization barrier of 8.52 kcal/ mol, compared with a value of 25.04 kcal/mol for the cyclization of... 

Evidence for the dicationic intermediates was also obtained from kinetic experiments involving the hydroxyester 57.32a The yield of the cyclization product (59) increases considerably with the acidity of the reaction media (Scheme 4). The fluorene product 59 is formed in appreciable quantities only in superacids Hq < —12). Following this observation, the kinetics of the fluorene cyclization was also studied in solutions of varying acidity. When compound 57 is reacted in solutions with acidity in the Hq — 11 to — 13 range, the cyclization rate is found to increase linearly with acidity. 

In addition to the above kinetics studies, the fluorene cyclization was studied using ab initio computational methods.323 It was found that the theoretically predicted barriers to the cyclizations for the dicationic intermediates agree well with the values obtained from the kinetic experiments. For example, geometry optimization and energy calculations at the B3LYP/6-31 level estimated that the activation energy (Ea) is 14.0 kcal/mol for the 4jt-electron conrotatory electrocyclization reaction involving compound 57 and the diprotonated intermediate (46, eq 13). 

The described superelectrophilic activation and fluorene-cyclization is thought to involve a lowered energy of the LUMO and concomitant delocalization of positive charge into the aryl ring(s).32b Calculations at the 4-31G//STO-3G level on a model system (Figure 2) have shown that the amount of positive charge in the phenyl ring increases upon formation of the dication (67) when compared to the monocation (66) and the benzyl cation (calculations are based on fully planar structures). It is well known... 

With the monocationic species, no fluorene cyclization is observed. However upon addition of CF3SO3H, the cyclization occurs almost quantitatively. This is consistent with formation of the protonated, dicationic intermediate (46) leading to the cyclization product (59). In this same study, it is noted that other stable monocationic 1,1-diarylethyl cations (i.e., the 1,1-diphenylethyl cation) do not readily form the fluorene ring system, indicating the importance of superelectrophilic activation. 

Besides the fluorene cyclization, the 1,2-ethylene dications are known to undergo another type of electrocyclization reaction to produce the phenan-threne ring system (see eqs 9 and 11 and Scheme 3).32a Although derived carbenium-carboxonium dications (70) will give the phenanthrene-type products (albeit in low yield eq 15), the bis-carboxonium dication 71 does not. Moreover, the fluorene cyclization occurs readily in 1,1-dihydroxylie systems (eq 10). 

Quaternization of harman (235) with ethyl bromoacetate, followed by cyclization of the pyridinium salt 236 with 1,2-cyclohexane-dione in refluxing ethanol yielded an ester which on hydrolysis gave the pseudo-cross-conjugated mesomeric betaine 237. Decarboxylation resulted in the formation of the alkaloid Sempervirine (238). The PCCMB 237 is isoconjugate with the 11/7-benzo[u]fluorene anion—an odd nonalternant hydrocarbon anion—and belongs to class 14 of heterocyclic mesomeric betaines (Scheme 78). 

Dichloroalkyl)chlorosilanes undergo the Friedel-Crafts alkylation type reaction with biphenyl in the presence of aluniinurn chloride catalyst to afford 9-((chlorosilyl)alkyl)fluorenes through two step reactions (Eq. (16)). The results obtained from the alkylation of biphenyl and the cyclization reaction to 5-membered-ring product are summarized in Table XIIE... 

The reactions presented below involve cyclization of an unfused biheterocycle at two ring nitrogen atoms adjacent to the torsional bond by an electrophilic reagent to give a fluorene analogue such as compound 197 from 2,2 -bipyridyl 196 (Equation 19) <1998AGE344>. 

The propargylic alcohol 102, prepared by condensation between 100 and the lithium acetylide 101, was efficiently reduced to the hydrocarbon 103, which on treatment with potassium tert-butoxide was isomerized to the benzannulated enyne-allene 104 (Scheme 20.22) [62], At room temperature, the formation of 104 was detected. In refluxing toluene, the Schmittel cyclization occurs readily to generate the biradical 105, which then undergoes intramolecular radical-radical coupling to give 106 and, after a prototropic rearrangement, the llJ-f-benzo[fo]fluorene 107. Several other HJ-f-benzo[fo]fluorenes were likewise synthesized from cyclic aromatic ketones. 

Treatment of the propargylic alcohol 144, readily prepared from condensation between benzophenone (143) and the lithium acetylide 101, with thionyl chloride promoted a sequence of reactions with an initial formation of the chlorosulfite 145 followed by an SNi reaction to produce in situ the chlorinated and the benzannulated enyne-allene 146 (Scheme 20.30) [62], A spontaneous Schmittel cyclization then generated the biradical 147, which in turn underwent a radical-radical coupling to form the formal [4+ 2]-cycloaddition product 148 and subsequently, after a prototropic rearrangement, 149. The chloride 149 is prone to hydrolysis to give the corresponding 11 H-bcnzo h fluoren-ll-ol 150 in 85% overall yield from 144. Several other llff-benzo[fc]fluoren-ll-ols were likewise synthesized from benzophenone derivatives. 

The foregoing examples of differential reactivities of rotamers may be summarized by saying that the reactivity is controlled by the steric factor. The difference in the reactivities of rotamers of 9-(2-bromomethyl-6-methyl-phenyl)fluorene (56) in SN2 type reactions falls in the same category (176). However, the substituent effect is not limited to a steric one there can be conformation-dependent electronic effects of substituents as well. A pertinent example is found in the reactivity of the bromomethyl compound (56) when the rotamers are heated in a trifluoroacetic acid solution (Scheme 10). The ap form gives rise to a cyclized product, whereas the sp form remains intact (176). The former must be reacting by participation of the it system of the fluorene ring. 

Methylfluorene has been prepared by cleavage of ethyl 9-methyl-9-fluorenylglyoxylate,4 by the decarboxylation of 9-methylfluorene-9-carboxylic acid,4 by the decarboxylation of 9-fluorenylacetic acid,6 by the cleavage of 9-methyl-9-acetyl-fluorene with alcoholic potassium hydroxide or soda-lime,6 by the reduction of 9-methyl-9-fluorenol with hydriodic acid in acetic acid,7 by the reaction of 9-fluorenyllithium 8 or -sodium 9 with methyl iodide or methyl sulfate,9 by the cyclization of diphenylmethyl carbinol over platinum-on-carbon at 300°,10 by the reaction of ethyl 9-methoxymcthyl-9-fluorcnylcarboxylate,11 by the diazotization and heating of 2-ethyl-2-aminobiphenyl,12 by the dehydration and then reduction of 9-mcthyl-9-fluorcnol,13... 

Interesting possibilities of synthesis arise when elimination leads to cyclic products. Such cyclization is fairly common with aromatic compounds. The mixture of products obtained from diphenylmethane contains about 25 per cent fluorene 2S> (Table 3). Similarly, benzophenone yields about 30 per cent fluorenone 20). The same method can be applied to the synthesis of heterocyclic compounds. Diphenylamine yields up to 30 per cent carbazol 26 di-phenylether about 10 per cent dibenzofurane 16). 

This is reasonably close to the experimentally determined value of AFF = 11.1 kcal/mol for the superelectrophilic cyclization of 62 (eq 12). Another computational study showed that the energy barriers dramatically decrease for the electrocyclization when the monocations are protonated to form superelectrophiles. In the case of 63, cyclization provides the acetyl-substituted fluorene in 70% yield from CF3SO3H (Scheme 5). At the B3LYP/6-31 level of theory, dication 64 is estimated to have a cyclization barrier to fluorene of 8.5 kcal/mol, compared to a value of 25 kcal/mol for the cyclization of monocation 65. 

A. From Biphenyl and Fluorene Derivatives 1. The Cyclization of 2-Substituted Biphenyls... 

Treatment of thiasalicylate with o-fluoro-a-bromoacetophenones in the presence of CS2CO3 affords 5-oxa-ll-thiabenzo[ ]fluoren-10-ones 204. The reaction involves formation and cyclization of intermediates 202, and subsequent intramolecular ( ro-fluorosubstitution of 203 (Scheme 40) <2001TL8429>. 

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