Conjugate addition ketones

Some examples of the synthetic usefulness of zincate reagents in organic synthesis are stereoselective alkylation reactions of cyclic ketones, conjugate-addition reactions... 

Chiral -substituted ketones Conjugate addition of (CH,)iAI to the kctal (2) of cyclohexenone derived from (S,S)-1 followed by acetylation results in the adduct 3, which is hydrolyzed by acid to (S)-3-mcthylcyclohcxanonc (4) in 77% ee. The ketal derived from (2R,3R)-2,3-butanediol undergoes a similai conjugate addition with low a.symmetric... 

There are two major reactions of organocuprates, and both give products reminiscent of a carbon nucleophile (1) reaction with alkyl halides and (2) conjugate addition with a,p-unsaturated ketones. Conjugate addition to a, 3-unsaturated ketones is promoted when ether is used as a solvent.381 The substitution reaction is promoted by the use of THF or ether-HMPA as a solvent. l As mentioned earlier, the mechanism of these reactions probably involves a one-electron transfer, although other mechanistic proposals are in the literature,but the synthetic result is that expected of a carbon nucleophile. 85 The general reactivity of organocuprates with electrophiles follows the order ... 

C—C Bond Formation using Organosilanes. Under catalysis by TiCU, allylsilanes transfer the allyl group, with rearrangement, to ketones, a/3-unsaturated ketones (conjugate addition), and quinones (initially giving the carbonyl addition product which then further rearranges to the 2-allyl-l,4-hydroquinone). But-3-enyl-silanes react with acid chlorides to yield cyclopropylmethyl ketones [reaction (3)) under similar conditions. 

Cinchonidine (99) has extended the substrate scope of the ketone conjugate additions to P-substituted methylidene malononitriles. In particular, the reaction of a-chloromethyl ketones, under very low loading conditions, affords tetrasubstituted cyclopropanes in moderate to good enantioselectivities after intramolecular cycliza-tion (Scheme 2.45) [142], A similar strategy has been followed to synthesize, with moderate to good enantioselectivities (56-90% ee) optically active naphlhopyran derivatives by a conjugate addition/cyclization sequence between 2-naphthol and a,a-dicyanoolefins [ 143 ]. 

FIGURE 18 7 Nucleophilic addition to a p unsaturated aldehydes and ketones may take place either in a 1 2 or 1 4 manner Direct addition (1 2) occurs faster than conjugate addition (1 4) but gives a less stable product The product of 1 4 addition retains the carbon-oxygen double bond which is in general stronger than a carbon-carbon double bond... 

A synthetically useful reaction known as the Michael reaction, or Michael addition, involves nucleophilic addition of carbanions to a p unsaturated ketones The most common types of carbanions used are enolate 10ns derived from p diketones These enolates are weak bases (Section 18 6) and react with a p unsaturated ketones by conjugate addition... 

The preparation and some synthetic applications of lithium dialkylcuprates were described earlier (Section 14 11) The most prominent feature of these reagents is then-capacity to undergo conjugate addition to a p unsaturated aldehydes and ketones... 

Outline two ways in which 4 methyl 2 octanone can be pre pared by conjugate addition of an organocuprate to an a p unsaturated ketone... 

P carbon atom of an a 3 unsatu rated carbonyl compound is elec trophilic nucleophiles especially weakly basic ones yield the prod ucts of conjugate addition to a 3 unsaturated aldehydes and ketones... 

Stabilized anions exhibit a pronounced tendency to undergo conjugate addition to a p unsaturated carbonyl compounds This reaction called the Michael reaction has been described for anions derived from p diketones m Section 18 13 The enolates of ethyl acetoacetate and diethyl malonate also undergo Michael addition to the p carbon atom of a p unsaturated aldehydes ketones and esters For example... 

The propensity for conjugate addition is diminished with A" -3-ketones due to steric hindrance. Thus A -3-alkyl ethers, as well as the corresponding thiobenzyl ethers and enamines, are formed selectively and in good yield from A" -3-ketones in the presence of 17- and 20-ketones. 

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