Additions to a,P-unsaturated carbonyl compounds

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... 

Aminopyrimidines are also known to undergo Michael additions to a,P-unsaturated carbonyl compounds. This methodology was utilized by Insuasty and co-workers using triaminopyrimidines 70 with conjugated ketones 71 to produce a variety of pyrimidine-fused diazepines 72 <00JHC193,00JHC401>. 

Scheme 12.11. Intermolecular addition to a,p-unsaturated carbonyl compounds.

Conjugate reduction.1 This stable copper(I) hydride cluster can effect conjugate hydride addition to a,p-unsaturated carbonyl compounds, with apparent utilization of all six hydride equivalents per cluster. No 1,2-reduction of carbonyl groups or reduction of isolated double bonds is observed. Undesirable side reactions such as aldol condensation can be suppressed by addition of water. Reactions in the presence of chlorotrimethylsilane result in silyl enol ethers. The reduction is stereoselective, resulting in hydride delivery to the less-hindered face of the substrate. 

You met organocopper reagents in Chapter 10 where you saw that they did conjugate additions to a,p-unsaturated carbonyl compounds. Other metals, such as cadmium or manganese, can also be used to make ketones from acid chlorides. 

This titanocene-catalyzed procedure was immediately extended by Gansauer et al. to the enantioselective opening of meso-epoxides by employing substoichiometric quantities of titanocene complexes with chiral hgands [58-60]. It has also been applied by this group in racemic form not only for reductive epoxide openings and intermolecular additions to a,P-unsaturated carbonyl compounds, but also to achieve 3-exo, 4-exo, and 5-exo cycliza-tions, as well as tandem cyclization addition reactions featuring vinyl radicals (Scheme 9) [8,9,44,46,57,61-65]. 

Stereocontrol in nucleophilic addition to carbonyl compounds 1.5.3.1.4 Addition to chiral alkoxycarbonyl compounds 1.53.1.5 Addition to a,p-unsaturated carbonyl compounds... 

Seteaive Addition to a,p-Unsaturated Carbonyl Compounds 1.823 Addition to C—N ir-Bonds... 

We end with a summary of the factors controlling the two modes of addition to a,P-unsaturated carbonyl compounds, and by noting that conjugate addition will be back again—in Chapters 23 (where we consider electrophilic alkenes conjugated with groups other than C=0) and 29 (where the nucleophiles will be of a different class known as enolates). 

Bernard , A., Capelli, A. M., Gennari, C., Scolastico, C. 1,4-Addition to a,P-unsaturated carbonyl compounds bearing a y-stereocenter a molecular mechanics model for steric interactions in the transition state. Tetrahedron Asymmetry 1990, 1,21-32. 

Addition to a,p-unsaturated carbonyl compounds. This reaction was an important step in syntheses of thioctic acid developed in two laboratories. A Lederle group" heated the ketone (2) with thiolacetic acid on the steam bath for 20 min. and obtained... 

Many additions to a,p-unsaturated carbonyl compounds, take advantage of coordination to the oxygen by a metal cation or a proton, or even just a hydrogen bond. This is true for hydrides and carbon nucleophiles. In such a situation, the LUMO coefficient is largest at the carbonyl carbon, but not at the p carbon. Thus, even soft nucleophiles can be expected to attack directly at the carbonyl carbon when Lewis or protic acid catalysis is involved. It is likely that the difference in the... 

Ammonia and amines undergo conjugate addition to a,p-unsaturated carbonyl compounds (Section 18.12). On the basis of this information, predict the principal organic prodnct of each of the following reactions ... 

More recent work has shown that the 2-unsubstituted compound 40 (R = H, R = PE) is an effective formyl anion equivalent which reacts at C2 and undergoes both 1,4-addition to a, P-unsaturated carbonyl compounds and 1,2-addition to aldehydes (93TL3907 96T4719). 

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