A- 3 Unsaturation 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... 

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

The general mechanistic features of the aldol addition and condensation reactions of aldehydes and ketones were discussed in Section 7.7 of Part A, where these general mechanisms can be reviewed. That mechanistic discussion pertains to reactions occurring in hydroxylic solvents and under thermodynamic control. These conditions are useful for the preparation of aldehyde dimers (aldols) and certain a,(3-unsaturated aldehydes and ketones. For example, the mixed condensation of aromatic aldehydes with aliphatic aldehydes and ketones is often done under these conditions. The conjugation in the (3-aryl enones provides a driving force for the elimination step. 

A stannaphosphene, Tip2Sn=PAr, was reacted with a series of a,/3-unsaturated aldehydes and ketones and, in all cases, was found to undergo exclusive [2 + 4] cycloaddition, leading to the corresponding six-mem-bered ring stannaoxaphosphorinenes (Scheme 9).1,5 An ene reaction is observed between the stannaphosphene and acetone.8... 

Dick et al. [88] studied the antioxidant effects of NADPH-dependent alkenal/one oxidor-eductase (AO), also known as leukotriene B4 12-hydroxydehydrogenase, 15-oxoprostaglan-din 13-reductase, and dithiolethione-inducible gene-1. It was found that AO catalyzed the hydrogenation of many a,(3-unsaturated aldehydes and ketones and protected against cytotoxic action of 4-hydroxy-2-nonenal. 

Very few enzyme-catalysed reactions involving the reduction of alkenes have achieved any degree of recognition in synthetic organic chemistry. Indeed the only transformation of note involves the reduction of a, (3-unsaturated aldehydes and ketones. For example, bakers yeast reduction of (Z)-2-bromo-3-phenylprop-2-enal yields (S)-2-bromo-3-phenylpropanol in practically quantitative yield (99 % ee) when a resin is employed to control substrate concen-tration[50]. Similarly (Z)-3-bromo-4-phenylbut-3-en-2-one yields 2(5), 3(,S)-3-bromo-4-phenylbutan-2-ol (80% yield, >95% ee)[51]. Carbon-carbon double bond reductases can be isolated one such enzyme from bakers yeast catalyses the reduction of enones of the type Ar—CH = C(CH3)—COCH3 to the corresponding (S)-ketones in almost quantitative yields and very high enantiomeric excesses[52]. 

The Fukui function for nucleophilic attack (/+) should be considered for nucleophilic addition reaction. Experimentally observed higher reactivity of the (3-position for nucleophilic attack on different a,(3-unsaturated aldehydes and ketones could be explained from the higher value of f+ for the 3-position than... 

Scheme 35 Imidazolidinone catalysed hydride reduction of a, 3-unsaturated aldehydes and ketones...

Over the last five years, we have designed, synthesized, and applied new ligands for asymmetric 1,2- and 1,4-addition reactions. Suitable ligands were found for the addition of alkyl-, aryl-, and alkenylzinc reagents to a,(3-unsaturated aldehydes and ketones, a-branched and unbranched aliphatic aldehydes, and imines. Although some substrates such as ketones and other carbonyl compounds have remained a challenge, we believe that this system provides an excellent entry into various classes of chiral intermediates. Application of these synthesized complex molecules is the current pursuit in our laboratories. 

The double bonds that are generally not affected by metallic hydrides may be isolated or conjugated, but double bonds that are conjugated with the C=0 group may or may not be reduced, depending on the substrate, reagent, and reaction conditions.252 Some reagents that reduce only the C=0 bonds of a,(3-unsaturated aldehydes and ketones are... 

When unsymmetrical ketones were used in this reaction (with BF3 as catalyst), the less highly substituted carbon preferentially migrated.188 The reaction can be made regioselective by applying this method to the a-halo ketone, in which case only the other carbon migrates.189 The ethyl diazoacetate procedure has also been applied to the acetals or ketals of a, (3-unsaturated aldehydes and ketones.190... 

Aldol condensation offers an effective route to a,(3-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 in Figure 18.6, the tt systems of the carbon-carbon and carbon-oxygen double bonds overlap to form an extended it system that permits increased electron delocalization. 

The diminished it electron density in the double bond makes a,(3-unsaturated aldehydes and ketones less reactive than alkenes toward electrophilic addition. Electrophilic reagents—bromine and peroxy acids, for example—react more slowly with the carbon-carbon double bond of a,(3-unsaturated carbonyl compounds than with simple alkenes. 

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, 3-unsaturated aldehydes and ketones. 

---