Cyclohexadienones addition reactions

The example of the thiol addition reaction to a cyclohexadienone indicates that discrimination of this type can be carried out catalytically the proximity of the meso carbon to the reaction center increases the stereoselectivity substantially. 

I 7 Copper-catalyzed Enantioselective Conjugate Addition Reactions of Organozinc Reagents Tab. 7.4. Conjugate additions to 2,5-cyclohexadienone monoacetals and ethers. 

The tandem arylrhodation/conjugate addition reaction, rhodium-catalyzed asymmetric arylative cyclization of cyclohexadienone-containing meso-l,6-dienynes was efficiently developed to provide optically pure d5-hydrobenzo[f ]furans with high to excellent yields and excellent enantioselectivities (13AGE5314). 

As one would expect, conjugated ketones are mostly poor hydrogen abstractors. This is a fortunate circumstance, because it leaves room for a variety of reactions that are quite useful from the preparative point of view. These include rearrangements [24], addition reactions and 2+2 cycloaddition with alkenes. An example of rearrangement of a cross-conjugated cyclohexadienone is shown above. This gives a cyclopropylcyclopentenone that opens up in the reaction medium (see Scheme 2.13). 

Lin and Tian developed a rhodium-catalyzed asymmetric arylative cyclization of cyclohexadienone-containing prochiral 1,6-dienynes 170 through a tandem arylrhodation/conjugate addition reaction (Scheme 2.44). This reaction could provide optically pure dy-hydrobenzofurans 172 with high to excellent yields (80-99%) and excellent enantioselectivities (95-99% ee). Furthermore, the cyclization products could also be transformed to interesting chiral frameworks of some natural products, thus demonstrating the utility of the products [63]. 

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. 

Nucleophilic additions to (cyclohexadienone)Fe(CO)3 complexes (218) occur in a dia-stereospecific fashion (Scheme 56)197. For example, the Reformatsky reaction of ketone (218a) affords a simple diasteromeric alcohol product19715. The reduction of (1-carbo-methoxycyclohexa-l,3-dien-5-one)Fe(CO)3 (218b) to give 219 has been utilized in the enantioselective synthesis of methyl shikimate. In a similar fashion, cycloadditions of (2-methoxy-5-methylenecyclohexa-l,3-diene)Fe(CO)3 (220) occur in a diastereospecific fashion198. 

As with Michael additions to activated alkenes, the initial adducts with activated alkynes can be trapped by various processes. An aldol reaction can occur if a carbonyl is properly situated in the starting material (Scheme 71).123 However, the use of methyl ethynyl ketone (509) and its homologs in the Robinson annulation process to give cyclohexadienones (510 equation 110) usually proceeds in poor... 

The occurrence of a similar reaction has recently been indicated by studies carried out in this laboratory (7). If p-hydroxybenzyl alcohol (XXXVI) was oxidized with sodium bismuthate, the spirocyclic epoxy-cyclohexadienone (XXXVII) was obtained. The epoxide ring of this compound was hydrolyzed almost instantaneously by 2N aqueous hydrochloric acid and in a few hours by 10% aqueous acetic acid. However, the expected glycol (XXXVIII) could not be isolated since it decomposed immediately into equimolar amounts of hydroquinone and formaldehyde. (Attempts are now being made to prepare compounds analogous to XXXVIII but containing, in addition to the HOCH2 group, a carbon sub-... 

Since OH is strongly electrophilic, the OH group directs OH into its ortho- and para-positions [reactions (51)—(53)]. One of the ortho-positions is occupied by the somewhat bulky carboxylate group which renders reaction (51) less likely than reaction (52). An addition to the meta-position can be largely neglected. Upon oxidation of the OH-adduct radicals, cyclohexadienones are formed [reactions (54)-(56)] which either decarboxylate [reaction (57)] or rearrange into the corresponding phenols [reactions (58) and (59) e.g., Bausch et al. 1976]. Product yields from hydroxybenzoic acids are compiled in Table 3.5 from salicylic acid in Table 3.6. 

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

Addition of alkynes to [2-(amino)alkenyl]carbene complexes ( )-96a does not afford cyclohexadienones (as might have been anticipated in case of a DOtz-type reaction),3 but gives cyclopentadienes 101 instead (Scheme 35) 3r,9a,9h jt js imp0rtant to note that the assembly of the cyclopentadiene... 

Conjugate addition to conjugated dienones. Marshall and co-workers have studied the reaction of the reagent wdth cyclohexadienones and conclude that stcric factors account for the ratio of 1,4- to 1,6-addition. The last two examples illustrate the virtual absence of angular methylation. 

In 2009, the Magnus group disclosed the synthesis of racemic codeine [50]. In their synthesis (1) an intramolecular phenol alkylation generating an A-C bicyclic ring system with a quaternary carbon, (2) a stereo-controlled, one-pot formation of a B-ring by way of the combination of Henry reaction and Michael addition of nitromethane with a cyclohexadienone-aldehyde, and (3) an introduction of the requisite functionalities in the C-ring by the epoxide-mediated selenylation followed by oxidation, were employed as the key transformations. 

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