4.4- disubstituted cyclohexadienone

Acid-promoted rearrangement of 4,4-disubstituted cyclohexadienones to 3,4-disubstituted phenols. 

Enantioselective copper phosphoramidite-catalyzed conjugate addition of dialkylzinc reagents to several 4,4-disubstituted cyclohexadienones is achieved with diastereomeric ratios ranging from 1/1 to 99/1 with 85% to 99% ee. When the two substituents are equal (eq 2), selective Re versus Si face-selective addition of the zinc reagent affords a single isomer. Sequential catalytic 1,4-addition to the prochiral dienones gave cis or trans bis-adducts with high enantio and diastereoselectivity. ... 

Silvero, G., Lucero, M. J., Winterfeldt, E., Houk, K. N. Theoretical study of the facial selectivity in Diels-Alder reactions of 4,4-disubstituted cyclohexadienones. Tetrahedron 1998, 54, 7293-7300. 

Cycloaddition of the diene 20 with dienophiles bearing a phenyl sulfoxide substituent leads, after elimination of phenyl sulfenic acid and hydrolysis, to a 4,4-disubstituted cyclohexadienone or a substituted phenol product. For example, an elegant synthesis of disodium prephenate 34 makes use of this chemistry... 

Transformation of a 4,4-disubstituted cyclohexadienone into a 3,4-disubstituted phenol upon acid treatment ... 

C. Reactions of 4,4>Disubstituted Cyclohexadienones and Related Compounds Derived from Octahydroindole Bases... 

A very good example of such a process is the rearrangement " " of 4,4-disubstituted cyclohexadienones [e.g., (11)] to bicyclohexenones [e.g., (15)]. It is fairly certain that the reaction follows the general path indicated below. Excitation (n- n ) of (11) gives (12), which then undergoes dis-rotatory electrocyclization to (13), which is formally an n n excited form... 

Disubstituted cyclohexadienones undergo Diels-Alder reactions more slowly than the unsubstituted counterparts. Thus 12 does not react with pipcrylene (13) at 180°, but in the presence of SnCl4 the reaction proceeds in 85% yield at 25°. Moreover a complete reversal of face selectivity can be achieved by use of a Lewis acid catalyst. Thus 15 reacts thermally with 13 to give 16, whereas the catalyzed reaction results in 17. Thus the stereochemistry of four asymmetric centers can be controlled.5... 

Oxidative dearomatization of 4-substituted phenols 222 with [bis(acyloxy)iodo]arenes in the presence of an external nucleophile provides a convenient approach to various 3,3-disubstituted cyclohexadienones 224 according to Scheme 3.92. Several examples of this reaction are provided below in Schemes 3.93-3.97. 

Polymerization Mechanism. The mechanism that accounts for the experimental observations of oxidative coupling of 2,6-disubstituted phenols involves an initial formation of aryloxy radicals from oxidation of the phenol with the oxidized form of the copper—amine complex or other catalytic agent. The aryloxy radicals couple to form cyclohexadienones, which undergo enolization and redistribution steps (32). The initial steps of the polymerization scheme for 2,6-dimethylphenol are as in equation 6. 

Synthesis of [1,2,3]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-c]pyrimidines A novel approach to [l,2,3]triazolo[l,5-c]pyrimidines is shown in Scheme 55. Batori and Messmer - in the course of their investigations on fused azolium salts - described a synthetic pathway to l,3-disubstituted[l,2,3]triazolo[l,5-c]-pyrimidinium salts <1994JHC1041>. The cyclization was accomplished by transformation of the hydrazone 436. This compound was subjected to an oxidative ring closure by 2,4,4,6-tetrabromo-2,5-cyclohexadienone to give the bicyclic quaternary salt 437 in acceptable yield. 

Disubstituted 2,4-cyclohexadienones (112) undergo photoinduced electrocyclic ring opening to the transient ketene derivatives 113, which can be trapped by nucleophiles to prepare the corresponding carboxylic acid derivatives (114 equation 44)196 197 j le reaction has been employed successfully for the synthesis of various carboxylic acids, esters and amides. 

If the Ddtz benzannulation reaction is conducted with ori/zo-disubstituted aryl-carbene complexes, the final aromatization step is blocked and cyclohexadienones can be isolated (Figure 2.34) [356,378,379]. 

Fig. 2.34. Formation of cyclohexadienones from 2,2-disubstituted vinylcarbene complexes.

Disubstituted-2,4-Cyclohexadienones. Irradiation of 6-ace-toxy-6-methyl-2,4-cyclohexadienone (Formula 92) (R = OAc R = Me) in ether containing water gives the unsaturated acid (Formula 93) (R = OAc R = Me) in 79% yield (48). The geometric arrangement of R and... 

Cyclobutenones. Cyclobutenones and cyclobutenediones undergo photochemical rearrangement to unsaturated acids in a manner analogous to that of 6,6-disubstituted-2,4-cyclohexadienones. Irradiation of Formula 133 in ether saturated with water gives Formula 134 (49). In... 

Disubstituted phenols such as 350 undergo PhI(OAc)2-mediated oxidation in the presence of MeOH as a nucleophile resulting in the formation of two possible cyclohexa-dienones (351 and 352) (Scheme 73). The initially formed intermediate 353 is converted to the cyclohexadienones by two plausible routes. In route A, heterolytic dissociation generates a solvated phenoxonium ion 354, which further reacts with MeOH to afford 351 and/or 352. In route B, both 351 and 352 are produced by direct attack of MeOH on the intermediate (353). In the latter case, the reaction will be strongly influenced by steric factors and a homochiral environment using chiral solvents and chiral oxidants to induce some asymmetric induction, particularly in the formation of 352. 

Conjugate addition. A phosphoramidite ligand (1) is useful for chiral induction during reaction of organozinc reagents with enones and 4,4-disubstituted 1,5-cyclohexadienones in the presence of Cu(OTf)2. 

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