1.4- Cyclohexadienones intermediates

Claisen rearrangement (Section 24 13) Thermal conversion of an allyl phenyl ether to an o allyl phenol The rearrange ment proceeds via a cyclohexadienone intermediate... 

Like the Diels-Alder reaction discussed in Sections 14.4 and 14.5, the Claisen rearrangement reaction takes place through a pericyclic mechanism in which a concerted reorganization of bonding electrons occurs through a six-membered, cyclic transition state. The 6-allyl-2,4-cyclohexadienone intermediate then isomerizes to o-allylpbenol (Figure 18.1). 

Rawal s group developed an intramolecular aryl Heck cyclization method to synthesize benzofurans, indoles, and benzopyrans [83], The rate of cyclization was significantly accelerated in the presence of bases, presumably because the phenolate anion formed under the reaction conditions was much more reactive as a soft nucleophile than phenol. In the presence of a catalytic amount of Herrmann s dimeric palladacyclic catalyst (101) [84], and 3 equivalents of CS2CO3 in DMA, vinyl iodide 100 was transformed into ortho and para benzofuran 102 and 103. In the mechanism proposed by Rawal, oxidative addition of phenolate 104 to Pd(0) is followed by nucleophilic attack of the ambident phenolate anion on o-palladium intermediate 105 to afford aryl-vinyl palladium species 106 after rearomatization of the presumed cyclohexadienone intermediate. Reductive elimination of palladium followed by isomerization of the exocyclic double bond furnishes 102. 

The last step of the reaction is the keto-enol tautomerization from T 4-cyclohexadienone intermediates (15) to aromatic products (16). Such a step is accompanied with a considerable gain in energy about 80 kJ mol 1 for vinylcarbenes [29], (where a phenol system is formed by the tautomerization step), and about 175 kJ mol 1 for phenylcarbenes [25] (where a naphtol system is produced). The energy barrier for such step should be lower than 40 kJ mol 1 according to previous calculations on similar systems [42],... 

Transient 4-bromo-2,5-cyclohexadienone intermediates are also clearly observed in the aqueous bromination of phenol1045. Addition products are occasionally noticed with less activated aromatic systems. Thus, in the chlorination of para-xylene in acetic acid, dichloroxylenes have been found to form directly via an ipso mechanism1046. 

The mechanism proposed by Ddtz involves the insertion of a carbon monoxide into the vinyl carbene complex intermediate with the formation of the vinyl ketene complex (255). Electrocyclic ring closure of (255) leads to the cyclohexadienone complex (252), which is related to the final tenzannulation product by a tautomerizadon when R is hydrogen. The mechanism proposed by Casey differs from that of Ddtz in that the order of the steps involving carbon monoxide insertion and cyclization to the aryl or alkenyl substiment is reversed. < Specifically, the vinyl carbene complex intermediate (248) first undergoes cyclization to the metallacyclohexadiene (249), followed by cartion monoxide insertion to give the intermediate (251), and finally reductive elimination to give cyclohexadienone intermediate (252). At this time the circumstantial evidence favors the intermediacy of vinyl ketene intermediates since they can be trapped from these reactions and isolated where the metal is dispaced from the vinyl ketene functionality however, there is not any evidence which can rule out the alternative mechanism. 

A series of papers devoted to rearrangements of cyclohexadienone intermediates formed upon bromination and chlorination of phenols was published °. The migration tendency... 

Photolysis of benzene solutions of l-methoxycarbonyl-2-naphthylmethyl 2,6-di-methyl substituted phenyl ethers induces C-O cleavage with formation of 2,4-cyclohexadienone intermediates which are subsequently photo-rearranged into meta substituted phenols. In methanol, 9-anthrylmethoxy-pyrid-2-one or l-pyrenylmethoxypyrid-2-one undergo photoheterolysis to give the C-O heterolysis products l-hydroxypyrid-2-one and the arylmethyl methyl ether, together with 2-pyridone, aryl-substituted methanol and aryl aldehyde derived from homolysis of the N-O bond. Evidence shows that an intramolecular exciplex plays a crucial role in C-O bond heterolysis. 

Formation of a trimethyltropone has been described by the transformation of the cyclohexadienone intermediate formed in the Reimer-Tiemann reaction in 59% yield from 2,4,6-trimethylphenol, chloroform and a little cetyltrimethylammonium bromide by treatment dropwise at 50°C over 10 mins, with aqueous sodium hydroxide. Refluxing of the cyclohexadienone for 4 hours with tributyltin hydride in benzene containing azoisobutyronitrile (AIBN) afforded 2,4,7-trimethyltropone in quantitative yield (ref.63). 

The structural features embodied in the Sceletium alkaloids coupled with evidence from biosynthetic studies suggest that cyclohexadienone intermediates may be involved in the biosynthesis of these alkaloids. In an attempt to isolate such intermediates, a procedure was devised for the isolation of phenolic alkaloids from 5. namaquense which avoided the use of acidic conditions which might be expected to induce rearrangement of acid-sensitive cyclohexadienone systems. This procedure involved washing a chloroform... 

Step 1 Sigmatropic shift. Redistribution of six electrons in a cyclic transition state gives a cyclohexadienone intermediate. Dashed red lines indicate bonds being formed in the transition state, and dashed blue lines indicate bonds being broken. 

Step 1 Make a new bond between a nucleophile (arene ring) and an electrophile. The phenoxide ion reacts like an enolate anion it is a strong nucleophile. Nucleophilic attack of the phenoxide anion on a carbonyl group of carbon dioxide gives a substituted cyclohexadienone intermediate. 

Step 2 Keto-enol tautomerism. Keto-enol tautomerism of the cyclohexadienone intermediate gives the product salicylate anion. Note that in this case, the enol, owing to its aromatic character, is the more stable of the two tautomers. 

Section 24 13 On being heated allyl aryl ethers undergo a Claisen rearrangement to form o allylphenols A cyclohexadienone formed by a concerted six tt electron reorganization is an intermediate... 

A second process that occurs concurrently with the dissociation— redistribution process is an intermolecular rearrangement by which cyclohexadienone groups move along a polymer chain. The reaction maybe represented as two electrocycHc reactions analogous to a double Fries rearrangement. When the cyclohexadienone reaches a terminal position, the intermediate is the same as in equation 8, and enolization converts it to the phenol (eq. 9). 

The procedure described is essentially that of Belleau and Weinberg and represents the only known way of obtaining the title compound. One other quinone acetal, 1,4,9,12-t6traoxadispiro[4.2.4.2]tetradeea-6,13-diene, has been synthesized by a conventional method (reaction of 1,4-cyclohexanedione with ethylene glycol followed by bromination and dehydrobromination ) as well as by an electrochemical method (anodic oxidation of 2,2-(l,4-phenylenedioxy)diethanol ). Quinone acetals have been used as intermediates in the synthesis of 4,4-dimethoxy-2,5-cyclohexadienone,. syw-bishomoquinone, - and compounds related to natural products. ... 

Structural analogues of the /]4-vinylketene E were isolated by Wulff, Rudler and Moser [15]. The enaminoketene complex 11 was obtained from an intramolecular reaction of the chromium pentacarbonyl carbene complex 10. The silyl vinylketene 13 was isolated from the reaction of the methoxy(phenyl)-carbene chromium complex 1 and a silyl-substituted phenylacetylene 12, and -in contrast to alkene carbene complex 7 - gave the benzannulation product 14 after heating to 165 °C in acetonitrile (Scheme 6). The last step of the benzannulation reaction is the tautomerisation of the /]4-cyclohexadienone F to afford the phenol product G. The existence of such an intermediate and its capacity to undergo a subsequent step was validated by Wulff, who synthesised an... 

When dienones 39 and 40 are photolyzed in sulfuric acid they both rearrange to the same product, 2-methyl-5-hydroxybenzaldehyde (41) (Filipescu and Pavlik, 1970). The mechanism for this photorearrangement is consistent with that of the protonated cyclohexadienones already discussed, i.e., disrotatory closure to afford the intermediate bicyclic cations 42 and 43. In this case it is conceivable that the electron-withdrawing effect of the dichloromethyl group forces the subsequent thermal cyclopropyl migration entirely in the direction of the most stable cation 44 to yield the observed product. 

Wang used method D to fashion a key intermediate for the synthesis of rishirilide B (Fig. 4.20).21 The 2,4-bis-OBoc-3-methyl-benzyl alcohol (31) undergoes the addition of two equivalents of corresponding Grignard reagent to afford phenol 32 in 75% yield (Fig. 4.20). This material was subsequently elaborated by Mejorado in three steps (61% yield) to the corresponding 2,5-chiral cyclohexadienone 33, which was ultimately transformed into ( + )-rishirilide B (34).22... 

The initially formed cyclopropyl ketones from the photolysis of cross-conjugated cyclohexadienones are also photolabile. Usually the photochemical rearrangements of cyclopropyl ketones involve cleavage of the cyclopropyl bond which forms part of the cyclopentenone ring followed by either (a) a substituent migration or (b) rearrangement through a spiro intermediate. While the literature in this area is too voluminous to review in... 

Schuster and Brizzolara<61> have provided a very nice study of the photochemistry of 10-hydroxymethyl-A1 9-2-octalone (87). Schuster and Patel<13) previously used radical fragmentation reactions as probes for the nature of the intermediates in the cyclohexadienone rearrangement. This compound (87) was designed so that it could undergo a radical fragmentation reaction in competition with the usual type A rearrangement if the intermediate involved has radical character (n -> n triplet). Photolysis produced (88)—(92) ... 

Analogous olefin trapping chemistry employing 2,7-cyclooctadienone has been investigated51. With this substrate, the oxyallyl zwitterion 112 could be intercepted intermolecularly with simple alkenes in a (presumably stepwise) 3 + 2 manner (Scheme 27). Importantly, intermediate 112 differs from 2,5-cyclohexadienone-derived zwitterions in terms of its lack of a facile rearrangement pathway. An interesting side-issue... 

Pyran-4-ones bear an obvious structural similarity to the all-carbon cyclohexadienones discussed above. However, the original studies of their photochemical behavior revealed only dimerization processes to produce a cage product resulting from two successive head-to-tail [2 + 2]-photocycloadditions (Scheme 29)54. Much later, small amounts of substituted furfural 121 were observed during the irradiation of 11955a. It was speculated that 121 could arise from bicyclic epoxide 120, an intermediate analogous to those formed in cyclohexadienone photochemistry. Subsequent reports noted that further irradiation of... 

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