Substitution 2,3-disubstituted cyclohexenones

The addition of carbon nucleophiles to complex (27), followed by demetallation, is equivalent to the y-alkylation of cyclohexenone. This overall transformation can also be accomplished directly via addition of electrophiles to dienolsilanes, but it becomes nontrivial for cases where the cyclohexenone C-4 position is already substituted.37 On the other hand, 1 -substituted cyclohexadienyliron complexes, such as (30), react very cleanly with certain carbon nucleophiles, at the substituted dienyl terminus. This provides useful methodology for the construction of 4,4-disubstituted cyclohexenones, and has been employed in a variety of natural product syntheses. 

The reaction of 2,2-disubstituted 1,3-cyclohexanediones 1 with dimethyl methanephosphonate in THF in the presence of LDA gives 3-substituted 2-cyclohexenones 2 in moderate to very good yields. 

Cyclohexadiene-Fe(CO)i complexes. Pearson has reviewed the formation and reactions of these complexes. One particularly inteiesting property is the ability of a methoxy group to direct attack of nucleophiles to the / disubstituted cyclohexenones (3), including spirocyclic compounds. 

The foregoing work suggests that the 3-substituted cyclohexenones (72) and (75) are kinetically favored in the cyclization of diketones (71) and (74), but that sufficiently vigorous conditions might cause isomerization to the 2,3-disubstituted cyclohexenone (e.g. 72 73). The fact that (75) does not undergo... 

A multistep conversion of 2,2-disubstituted 1,3-cyclohexadiones 191 to 3-substi-tuted 2-cyclohexenones 192 mediated by phosphonate anions was applied by Yamamoto and Furuta [69] in a formal synthesis of ( )-a-acoradiene (193) (Scheme 47). 3-Substituted 2-cyclohexenones are versatile building blocks for the synthesis of cyclic natural products such as spirocyclic and fused ring sesquiterpenes. These cyclohexenones were easily obtained in a one-pot reaction of 194 with dimethyl methanephosphonate anion in the presence of trimethylsilyl chloride. The new overall reaction is a multistep rearrangement involving... 

We have found that 4-isobutenyl-dienone cyclizations can also produce cycloheptanes under fluoride ion catalysis provided that the C(4) position is substituted only with the allylsilane-containing side chain (Eq. 12). As mentioned earlier, C(3),C(4)-disubstituted cyclohexenones prefer a conformation with the C(4) substitutent orient axially. In this situation the absence of an equatorial C(4) substitutent favors a transoid con-... 

Cycloalkenones. The nucleophilic at disubstituted 1,3-cycloalkanediones re Wadsworth reaction to give 3-substituted 2 The reaction of the same reagent wit phonates), which may undergo cyclization. rapid aldolization, permitting subsequent a 2-cyclohexenones. 

Based on initial studies by Krause and Alexakis [100], the highly enantioselective synthesis of trans-5-aryl-2-substituted cyclohexanones 119 was accomphshed by the conjugate arylation of racemic 6-substituted cyclohexenones 117 (Scheme 8.29) [101]. Although the first step did not proceed in a diastereoselective maimer, only the thermodynamically more stable trans-disubstituted cyclohexanone 119 was obtained after epimerization with NaOEt. 

Reactions with a,jS-Unsaturated Compounds. If the carbonyl is a, -unsaturated, reaction takes place at the alkene via addition/substitution to form em-dimethyl-substituted cyciopropanes. For example, the em-disubstituted cyclopropane was prepared from cyclohexenone in 74% yield (eq 6). ... 

In summary, the mesyl triflone reagent is useful for preparing 1,1-disubstituted aUcenes (eq 1) (R = R = H) or cyclopen-tenones such as dihydrojasmone. However, cyclohexenones were not formed and, while more substituted acyclic alkenes are readily obtained, they arise as ds-fraws mixtures. 

Kinney WA, Crouse GD, Paquette LA. Regiocontrolled synthesis of monosubstituted, disubstituted, and tri-substituted cyclohexenones by cycloaddition of vinyl sulfones to l-methoxy-3-[(trimethylsilyl)oxy]-l,3-butadienes conversion of alkenes into effective dienophilic reagents. J. Org. Chem. 1983 48(25) 4986-5000. 

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