Ketone Unsaturated, conjugate addition

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... 

This is a fairly difficult problem because it is not obvious at the outset which of the two possible enolates of benzyl ethyl ketone undergoes conjugate addition to the o,/3-unsaturated ketone. A good idea here is to work backward from the final product—in effect, do a ret-rosynthetic analysis. The first step is to recognize that the enone arises by dehydration of a /Thydroxy ketone. 

Asymmetric Michael additions The anions of hydrazones (2), obtained from 1 and methyl ketones, undergo conjugate addition to a,p-unsaturated esters with virtually complete 1,6-asymmetric induction to give the adducts (S,R)-3. Ozonolysis converts these products into P-substituted 8-keto esters, (R)-4, obtained in optical yields of 96-l(X)%, with recovery of the chiral auxiliary as the nitrosamine (S)-5. The overall chemical yields of 4 are 45-62%. 

Alcohols add to conjugated ketones with a PMe3 catalyst to give the p-alkoxy ketone.The conjugate addition of peroxide anions (HOO and ROO ) to cx,p-unsaturated carbonyl compounds is discussed in 15-48. 

Conjugate Addition Reactions. a, 8-Unsaturated ketones undergo conjugate addition with TMS-I to afford the /3-iodo... 

The Michael reaction is an alkylation in which carbanions, such as the enolates derived from (3-diketones, p-keto esters, and diethyl malonate, react with a,p-unsaturated ketones by conjugate addition. The a,p-unsaturated ketone serves the same kind of electrophilic role that alkyl halides do toward the enolate. 

The p carbon of an a,p-unsaturated carbonyl compound is electrophilic nucleophiles, especially weakly basic ones, react with a,p-unsaturated aldehydes and ketones by conjugate addition. The nucleophile bonds to the p carbon. 

Conjugate Addition. a. -Unsaturated ketones undergo conjugate addition with TMS-Br. Treatment of the intermediate with p Toluenesulfonic Acid and ethylene glycol provides p-bromoethyldioxolanes (eq 16). ... 

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... 

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... 

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