2-Cyclohexenone reaction with Grignard reagents

Ethoxy-2-cyclohexenone is a useful intermediate in the synthesis of certain cyclohexenones. The reduction of 3-ethoxy-2-cyclohexenone with lithium aluminum hydride followed by hydrolysis and dehydration of the reduction product yields 2-cyclo-hexenone. Similarly, the reaction of 3-ethoxy-2-cyclohexenone with Grignard reagents followed by hydrolysis and dehydration of the addition product affords a variety of 3-substituted 2-cyclo-hexenones. ... 

Chiral ferrocenylphosphine oxazoline 27 was also introduced as a ligand for the copper catalyst. The reaction of Grignard reagents with cyclohexenone afforded the product in 83% ee (Eq. (12.29)) [58]. 

This work was initiated in 1988 when Villacorta et al.71a reported the asymmetric conjugate addition of a Grignard reagent to 2-cyclohexenone. This study showed that 1,4-adducts with 4-14% ee were obtained in the presence of aminotroponeimine copper complex.713 Enhanced results (74% ee) were obtained by adding HMPA or silyl halides.71b Several other copper complexes were also used for inducing asymmetric conjugate addition reactions. Moderate results were obtained in most cases when THF was used as the solvent and HMPA as the additive. 

Organobis(cupratesY, spiroannelation.16 1,4-Dilithiobutane, prepared from 1,4-dichlorobutane and lithium in ether at 0°, on reaction with copper thiophenoxide (2 equiv.) forms a biscuprate, formulated as 1 for convenience. This dimetallic reagent adds to 3-halo-5,5-dimethyl-2-cyclohexenones (2) to form the spiro-[4.5]decanone 3 in yields as high as 96%. Cuprates prepared from other Cu(I) sources are less efficient, as is the cuprate prepared from di-Grignard reagents... 

Likewise, the reaction of a Grignard reagent with a cyclohexenone can result in either 1,2-addition to produce a substituted cyclohexenol (see Table 1, entry 18)... 

Organometallic reactions. In promoting reactions of Grignard and organolithium reagents with 2-cyclohexenone, chemoselectivity is solvent dependent. 

Addition of an acyl anion or its equivalmt to a,p-unsaturated ketones is an important synthetic mediod for 1,4-dicaibonyl compounds. In the palladium method for 1,4-dicartxHiyl compounds, a vinyl Grignard or vinyllithium reagent is used as a synthetic equivalent of the acetyl anion. Reaction of lithium divinylcuprate with 2-cyclohexenone (44) afforded 3-vinylcyclohexanone (45). which was oxidized to the 1,4-diketone (46 Scheme 12). ° ... 

---