1.3- Cydohexadienes

Aryl- or alkenylpalladium comple.xcs can be generated in situ by the trans-metallation of the aryl- or alkenylmercury compounds 386 or 389 with Pd(Il) (see Section 6). These species react with 1,3-cydohexadiene via the formation of the TT-allylpalladium intermediate 387, which is attacked intramolecularlv by the amide or carboxylate group, and the 1,2-difunctionalization takes place to give 388 and 390[322]. Similarly, the ort/trt-thallation of benzoic acid followed by transmetallation with Pd(II) forms the arylpalladium complex, which reacts with butadiene to afford the isocoumarin 391, achieving the 1,2-difunctionalization of butadiene[323]. 

FIGURE 11 2 Heats of hy drogenation of cydohexene 1 3 cydohexadiene a hypo thetical 1 3 5 cydohexa triene and benzene All heats of hydrogenation are in kilojoules per mole... 

Synthesis by oxidation remains the first choice for commercial and laboratory preparation of quinones the starting material (1) provided the generic name quinone. This simple, descriptive nomenclature has been abandoned by Chemicaly hstracts, but remains widely used (2). The systematic name for (2) is 2,5-cyclohexadiene-l,4-dione. Several examples of quinone synonyms are given in Table 1. Common names are used in this article. 1,2-Benzoquinone (3,5-cydohexadiene-l,2-dione) (3) is also prepared by oxidation, often with freshly prepared silver oxide (3). Compounds related to (3) must be prepared using mild conditions because of their great sensitivity to both electrophiles and nucleophiles (4,5). 

Cyeiohexenone (3). To a solution ol sodium (782 mg, 34 mmoQ, in MeOH (40 mL) was added at room temperature, and under N2 2-nitropropane 1 (3.94 g, 44 mmoQ arxJ then 3-bromocyciohexene 2 (5 5 g, 34 mmol). After 20 h, the solvent and cydohexadiene were distilled M atm. pressure, the residue was treated with water and ether, the organx layer washed with 10% solution ol NaOH, and water After drying over MgS04, the solvent was evaporated and the reddue distilled in vacuum There was obtained 3 as a colorless liquid, 1 43 g (44%)... 

C. 7 ricar6oni/Z[( 1,2,3,4,5-jj)-l-and 2-methoxy-2,4 -cydohexadien-l-yl]-irTriphenylmethyl tetrafluoroborate [Methylium, triphenyl-, tetrafluoroborate] (34 g., 0.103 mole) (Note 20) is dissolved in a minimum volume of dichloromethane and 18 g. (0.072 mole) of tricarbonyl (1- and 2-methoxy-l,3-cyclohexadiene)iron dissolved in a like volume of dichloromethane is added. The resulting dark solution is left for 20-30 minutes and then added with stirring to three times its volume of ether (Note 21). The precipitate is collected and washed with ether to 5ueld 21-22 g. (87-91%) of product as yellow solid (Note 19). 

E. Tricarbonyl[ 1,2,3,4,5-tj) -2-methoxy-2,4-cydohexadien-1 - Z]-iron(l +) Hexafliu)rophosphate(l —). To the aqueous layer from Part D is added with swirling 7.1 g. (0.044 mole) of ammonium hexafluoro-phosphate (Note 23) in 30 ml. water. After 30 minutes, the light-yellow product is filtered, washed with water, and air dried the yield is about 9-10 g. (35-447o) (Notes 19, 24). 

The ring expansions of cydohexadiene derivatives to azepines is of historical significance, as the first example of a monocyclic 1//-azepine was obtained by cyanide ion attack on 2-acetoxy-2,4,6-trimethyl-iV-(phenylsulfonyl)cyclohexa-3,5-dien-l-imine (4) 17 however, it was almost twenty years before the product was correctly formulated as the l//-azepine 5.24... 

Scheme 12.9 Reactions of cydohexadiene diepoxides with amines [2].

In a similar way to the addition of zirconacyclopentadienes to DMAD, their addition to methyl maleate gives cydohexadiene derivatives. It is noteworthy that the two COOMe groups are cis in the starting material and trans to one another in the product, as shown in Eq. 2.63 [7k]. 

The formulas of the substituted 1,2-cydohexadienes heretofore successfully generated and trapped are collected in Scheme 6.22. It seems that a theoretical study has been performed only with l-phenyl-l,2-cydohexadiene (75), predicting it to be a true allene with a C1-C2-C3 bond angle of 134° [76], which is very similar to that of 6. 

By chance, the existence of the borane complex 330 of 329 was discovered. The liberation of 330 occurred with the best efficiency with sodium bis(trimethylsilyl)-amide from the borane complex 327 of 326. When styrene or furan was used as the solvent, three diastereomeric [2 + 2]-cycloadducts 328 and [4 + 2]-cycloadducts 331, respectively, were obtained in 30and 20% yield (Scheme 6.70) [156]. With no lone pair on the nitrogen atom, 330 cannot be polarized towards a zwitterionic structure, which is why its allene subunit, apart from the inductive effect of the nitrogen atom, resembles that of 1,2-cydohexadiene (6) and hence undergoes cycloaddition with activated alkenes. It is noted that the carbacephalosporin derivative 323 (Scheme 6.69) also does not have a lone pair on the nitrogen atom next to the allene system because of the amide resonance. 

The positional selectivity of the cycloadditions of 351 is of particular interest, since the [2 + 2]-cydoadditions proceed exclusively at the double bond bearing the oxygen atom, whereas the [4 + 2]-cycloadditions occur at the double bond remote of the oxygen atom with the exception of the major product resulting from 1,3-cydohexadiene (369, Scheme 6.75). Supposing diradical mechanisms, these findings require that... 

Dehydrobromination of 173 with tBuOK gave rise to the l-oxa-2,3-cydohexadiene intermediate 174, which was trapped by furan to give the cycloadduct [142]. 

Asymmetric allylic C-H activation of cydohexadiene systems has been used for the asymmetric synthesis of several compounds of pharmaceutical relevance. The key step in the asymmetric syntheses of the monoamine reuptake inhibitor (-i-)-indatrahne 185 was the C-H insertion reaction of the aryldiazoacetate 183 with 1,4-cyclohexadiene (Scheme 14.24). The product 184, obtained in 83% yield with 93% enantiomeric excess, is readily converted to (-i-)-indatraline using standard synthetic procedures [132]. 

In Einzelfallen bietet sich die Ugi-Reaktion fur die Synthese bestimmter a-Amino-carbonsauren im Vergleich zu anderen Moglichkeiten als Methode der Wahl an. Beispiele sind die Herstellung von Bis-[l-carboxy-alkyl]-aminen I aus a-Amino-carbonsaure-estern8 [unter Verwendung von 4-Methyl-phenylsulfonylmethyl-isocyanid (TOSMIC)9 als Isonitril-Komponente] und die von 3-(2,5-Cyclohexadienyl)-alanin-methylamid(ll) (37% aus 3-Formylmethyl-l,4-cydohexadien)1. 

D. Trimrbonyl[(2,3,4 ,5-ri)-2, t-cydohexadien-l-(yne]iron. The mixture of tetrafluoroborate from Part C (21 g., 0.062 mole) is heated on a steam bath for 1 hour in 450 ml. of water, during which time orange crystals separate. After cooling, the mixture is extracted three times with 100-ml. portions of ether into which most of the solid dissolves. (The aqueous layer is used in Part E.) The extracts are dried over anhydrous magnesium sulfate, and the ether is evaporated to yield the yellow crystalline dienone complex, 7-7.5 g. (47-61%) (Note 22). 

Reduction. Benzene can be reduced to cyclohexane [110-82-7], C5H12, or cycloolefins. At room temperature and ordinary pressure, benzene, either alone or in hydrocarbon solvents, is quantitatively reduced to cyclohexane with hydrogen and nickel or cobalt (14) catalysts. Catalytic vapor-phase hydrogenation of benzene is readily accomplished at about 200°C with nickel catalysts. Nickel or platinum catalysts are deactivated by the presence of sulfur-containing impurities in the benzene and these metals should only be used with thiophene-free benzene. Catalysts less active and less sensitive to sulfur, such as molybdenum oxide or sulfide, can be used when benzene is contaminated with sulfur-containing impurities. Benzene is reduced to 1,4-cydohexadiene [628-41-1], C6HS, with alkali metals in liquid ammonia solution in the presence of alcohols (15). 

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