Unsaturated aldehyde, conjugate

Unimolecular, 373 Unsaturated, 174 Unsaturated aldehyde, conjugate addition reactions of,... 

Analogous to conjugated unsaturated aldehydes, conjugated unsatur-ted ketones react after the above scheme to saturated ketones [35] (table 17). 

Solution to 23a A compound with the correct six-carbon skeleton can be obtained if a three-carbon aldehyde undergoes an aldol addition. Dehydration of the addition product forms an a,/3-unsaturated aldehyde. Conjugate addition of HBr (Section 17.18) forms the target molecule. 

Conjugation of the newly formed double bond with the carbonyl group stabilizes the a p unsaturated aldehyde provides the driving force for the dehydration and controls Its regioselectivity Dehydration can be effected by heating the aldol with acid or base Normally if the a p unsaturated aldehyde is the desired product all that is done is to carry out the base catalyzed aldol addition reaction at elevated temperature Under these conditions once the aldol addition product is formed it rapidly loses water to form the a p unsaturated aldehyde... 

Aldol condensation offers an effective route to a p unsaturated aldehydes and ketones These compounds have some interesting properties that result from conjugation of the carbon-carbon double bond with the carbonyl group As shown m Figure 18 6 the rr systems of the carbon-carbon and carbon-oxygen double bonds overlap to form an extended rr system that permits increased electron delocalization... 

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... 

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... 

Ethynyl carbinols rearrange to conjugated unsaturated aldehydes. Copper or silver salts cataly2e isomeri2ation of the acetate to an aHenic acetate, which can be hydroly2ed to an unsaturated aldehyde (204). 

These reversible reactions are cataly2ed by bases or acids, such as 2iac chloride and aluminum isopropoxide, or by anion-exchange resias. Ultrasonic vibrations improve the reaction rate and yield. Reaction of aromatic aldehydes or ketones with nitroparaffins yields either the nitro alcohol or the nitro olefin, depending on the catalyst. Conjugated unsaturated aldehydes or ketones and nitroparaffins (Michael addition) yield nitro-substituted carbonyl compounds rather than nitro alcohols. Condensation with keto esters gives the substituted nitro alcohols (37) keto aldehydes react preferentially at the aldehyde function. 

This 1,3-migration of hydrogen was also observed when 40 reacted with Lawesson s reagent to produce the dithiolactone 41. However, when y-hydroxy-a,P-unsaturated aldehyde 42 was reacted under similar conditions, thiophene 43 was prepared efficiently. These results are not surprising considering that the oxidation state of 42 is equivalent to the traditional saturated 1,4-dicarbonyl substrates of the Paal thiophene reaction via tautomerization of the double bond, and aromaticity is reestablished in the fully conjugated 43. 

Conjugate Nucleophilic Addition to ,jB-Unsaturated Aldehydes and Ketones... 

The conjugate addition of a nucleophile to an a,fi-unsaturated aldehyde or ketone is caused by the same electronic factors that are responsible for direct addition. The electronegative oxygen atom of the a,/3-unsaturated carbonyl compound withdraws electrons from the /3 carbon, thereby making it electron-poor and more electrophilic than a typical alkene carbon. 

As noted previously, conjugate addition of a nucleophile to the j3 carbon of an cr,/3-unsaturated aldehyde or ketone leads to an enolate ion intermediate, which is protonated on the a carbon to give the saturated product (Figure 19.16). The net effect is addition of the nucleophile to the C=C bond, with the carbonyl group itself unchanged. In fact, of course, the carbonyl group is crucial to the success of the reaction. The C=C bond would not be activated for addition, and no reaction would occur, without the carbonyl group. 

Conjugate Nucleophilic Addition to a, /3-Unsaturated Aldehydes and Ketones 727... 

Both primary and secondary amines add to a /S-unsaturated aldehydes and ketones to yield /3-amino aldehydes and ketones rather than the alternative imines. Under typical reaction conditions, both modes of addition occur rapidly. But because the reactions are reversible, they generally proceed with thermodynamic control rather than kinetic control (Section 14.3), so the more stable conjugate addition product is often obtained to the complete exclusion of the less stable direct addition product. 

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