4.4.6- Trimethyl-2-cyclohexenone

Substituted /J--cvclohexenoaes such as 3,5,5-trimethyl-2-cyclohexenone (104) gave with pyrrolidine the corresponding enamine (105) (50a). 

To a solution of 6.99 g (25.3 mmol) of 2,3,4-trimethyl-4-(5-trimethylsilyl-3-pentynyl)-2-cyclohexenone in 150 mL of C HjClj are added at —78 C 5.1 mL (44 mmol) of TiCl4, and the resultant mixture is stirred for 30 min at —78 "C. The mixture is quenched at low temperature with 100 mL of water and extracted with three 50-mL portions of Ch,C12. The combined organic phase is washed with 150 ml, of brine and dried over MgS04. The solvent is removed in vacuo and the crude product is flash chromatographed (EtOAc/ petroleum ether 3 97) to give the pure product as a 2 1 mixture of diastcreomers yield 4.32 g (84%) d.r. 2 1. 

The reactions of the lithium enolates of substituted 2-cyclohexenones and 2-cyclopentenones with ( )-l-nitropropene give a mixture of syn- and ami-products3. The lithium enolate of 3,5,5-trimethyl-2-cyclohexenone gives a mixture of the syn- and //-3.5,5-trimethyl-6-(l-methyl-2-nitroethyl)-2-cyclohexcnoncs in modest diastereoselection when the reaction mixture is quenched with acetic acid after. 30 minutes at —78 =C. When the reaction mixture is heated to reflux, tricyclic products are obtained resulting from intramolecular Michael addition of the intermediate nitronate ion to the enone moiety. 

Reaction of 3,5,5-trimethyl-2-cyclohexenone with three equivalents of NaNH2 in THF generates the corresponding enolate. When bromobenzene is added and the solution stirred for 4 h, the product 10-1 is isolated in 30% yield. Formulate a mechanism for this transformation. 

Asymmetric Allylation. One of the recent new developments on this subject is the asymmetric allylation reaction. It was found that native and trimethylated cyclodextrins (CDs) promote enantiose-lective allylation of 2-cyclohexenone and aldehydes using Zn dust and alkyl halides in 5 1 H2O-THF. Moderately optically active products with ee up to 50% were obtained.188 The results can be rationalized in terms of the formation of inclusion complexes between the substrates and the CDs and of their interaction with the surface of the metal. 

Epoxide formation is nearly suppressed when massively subeti-tuted olefine, such as 2,2,4-trimethyl-3-hexene among others, ate subjected to the chromic oxide-acetic anhydride reagent,42 Cyclo-hexene yields primarily 2-cyclohexenone and cyclohexane- 1,2-dione777 although some cyclohexane oxide appears to bo formed also (Eq, 111). 

Hydrogenation of 2,4,4-trimethyl-2-cyclohexenone with rrans-RuCl2(tolbinap)(dpen) and (CH3)3COK under 8 atm of hydrogen gives 2,4,4-trimethyl-2-cyclohexenol quantitatively with 96% ee (Scheme 1.70) [256,275,276]. In this case, unlike in the reaction of aromatic ketones, the combination of the R diphosphine and S,S diamine most effectively discriminates the enantiofaces. The chiral allylic alcohol is a versatile intermediate in the synthesis of carotenoid-derived odorants and other bioactive terpens such as a-damascone and dihydroactinidiolide [277]. 

An interesting asymmetric activation of Ru complexes for enantioselective hydrogenation of ketones has been observed [65], Hydrogenation of 2,4,4-trimethyl-2-cyclohexenone using racemic RuCl2 (tolbmap)(dmf)n, (5,5)-DPEN and KOH (1 1 2) afforded the alcohol 107 with 95% ee in 100% yield. When (R)-TolBINAP and (S,S)-DPEN were used, the alcohol 107 with 96% ee was obtained. On the other hand, only... 

The infrared spectra of hydroiodides and perchlorates of such enamines indicate O-protonation one or two strong maxima occur in the 1600 cm-1 region and there is no absorption in the 1650-1800 cm-1 region as would be expected for the ammonium or immonium compounds. 2,5,5-Trimethyl-3-pyrrolidino-2-cyclohexenone and 5,5-dimethyl-3-pyrrolidino-2-cyclohexenone (41) are examples of compounds which form salts by O-protonation. In contrast,... 

Carbonyl-selective asymmetric hydrogenation of 2-cyclohexenone - a simple cyclic conjugated enone - is stdl difficult, but some substituted 2-cydohexenones such as 2,4,4-trimethyl-2-cyclohexenone, (R)-carvone, a chiral dienone, and (R)-pule-gone, an s-cis chiral enone have been used successfully [66, 68, 81b, 107]. 

The same type of process using osmylation instead of the Simmons-Smith reaction leads to a synthesis of enantiomerically pure 2,3-dihydroxycycloalkanones from 2-cycloalkenones. Addition of (S)-(141) to 3,S,S-trimethyl-2-cyclohexenone (162) produces a mixture of diastereomers (163a) and (163b), which are easily separable by silica gel chromatography. Treatment of the individual diastereomers with tri-ethylamine N-oxide and 0s04 (5 mol %) afford crude triols. In each case, a single diastereomeric product is produced. The subsequent thermolysis of the diastereomeric triols gives enantiomeric 2,3-dihydroxy-3,5,5-trimethyl-2-cyclohexanones(164 Scheme 37). 

Synonyms Isoacetophenone 1,1,3-Trimethyl-3-cyclohexene-5-one 1,5,5-Trimethyl-l-cyclo-hexen-3-one 3,5,5-Trimethyl-2-cyclohexen-l-one 3,5,5-Trimethyl-2-cyclohexenone 3,5,5-Trimethylcyclohex-2-enone 3,5,5-Trim-... 

For a related synthesis of 5- and 6-substituted cyclohexenones see 2,2,6-trimethyl-1,3-dioxolenone (this volume). 

Access to key materials for synthesis in this group has been possible for some years by reaction of acrolein with 2-methyl-3-pentanone in presence of p-toluenesulfonic acid, distilling off the water formed during the reaction, and leading to 2,6,6-trimethyl-2-cyclohexenone (690). Alternatively, 2-methyl-3-pentanone reacts with methyl acrylate in the presence of base (sodium methoxide/ methanol in xylene) to give 92% of the diketone 691 (probably as the enol). ... 

Intermolecular de Mayo reactions are efficient for cyclic 1,3-diketones such as dimedone (5,5-dimethyl-l,3-cyclohexanedione)96,103,104 and acyclic systems such as acetylacetone93-95. Unsymmetrical acyclic /l-diketones, such as 1-phenyl-1,3-butanedione98 can enolize in two directions, however, reaction normally occurs preferentially from a single enol form. Examples of alkene photocycloaddition to trapped ends of /(-dicarbonyl compounds (e.g., 2,2-dimethyl-3(2/f)-furanone and 2,2.6-trimethyl-4/f-l,3-dioxin-4-one) are given in Table 1 (entries 26, 27) and Table 2 (entry 35) 10°. If the enol is stabilized by derivatization (e.g., acetylated dimedone 3-acetoxy-5,5-dimethyl-2-cyclohexenone), the primary cyclobutane photoproducts can be isolated96. 

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