Carbonyl compounds conjugate addition to unsaturated

Prior to protonolysis, the products of conjugate addition to unsaturated carbonyl compounds are enolates and, therefore, potential nucleophiles. A useful extension of the conjugate addition method is to combine it with an alkylation step that adds a substituent at the a position.52 Several examples of this tandem conjugate addition/alkylation procedure are given in Scheme 8.2. 

In Chapter 10 we discussed conjugate addition to unsaturated carbonyl compounds in contrast to direct addition to the carbonyl group. A classic illustration is the addition of HCN to butenone. Two products can be formed. 

So far, most of the reactions presented in the book that are useful in synthesis have made C-O, C-N, or C-halogen bonds and only a few (Wittig, Friedel-Crafts, and reactions of cyanides and alkynes) make C-C bonds. This limitation has severely restricted the syntheses that we can discuss in this chapter. This is by design as we wanted to establish the idea of synthesis before coming to more complicated chemistry. The next four chapters introduce the main C-C bond-forming reactions in the chemistry of enols and enolates. You met these valuable intermediates in Chapter 21 but now you are about to see how they can be alkylated and acylated and how they add directly to aldehydes and ketones and how they do conjugate addition to unsaturated carbonyl compounds. Then in Chapter 30 we return to a more general discussion of synthesis and develop a new approach in the style of the last synthesis in this chapter. 

A useful application of these reagents is in conjugate addition to unsaturated carbonyl compounds. Few d1 reagents will do this as most arc very basic and prefer to add direcdy to the carbonyl... 

Coordination of carbonyl groups by Lewis acids accelerates simple carbonyl transformations, conjugate additions to unsaturated carbonyl compounds, and Diels-Alder reactions, by polarizing the carbonyl group. 

In these investigations, nucleophilic additions to carbonyl groups and carbonyl group equivalents as well as conjugate 1,4-additions to unsaturated carbonyl compounds have been of great value. In the 1,2-additions, aUyl tin-compounds showed interesting synthetic flexibility. They served well for carbonyl groups but also for acetals as is demonstrated with 316 and 317 [103],... 

Conjugate addition of hydroperoxide to unsaturated carbonyl compounds generates epoxide in the presence of superbases. Wood et al. conducted the epoxidation reaction of 183 by treatment with ferf-butyl-hydroperoxide, using a catalytic amount of DBU [55]. The resulting epoxide 184 was converted to ( )-epoxysorbicillinol (185) (Scheme 7.41). 

Asymmetric conjugate addition reactions of carbonyl compounds with a, -unsaturated systems are known. The simple amine a-methylbenzylamine 68 acts as both the activator (to give the imine and hence the enamine required for alkylation) and as the chiral auxiliary to effect neutral asymmetric conjugate-addition reactions. " Thus, condensation of (5)-a-methylbenzylamine 68 with 2-methylcyclohexanone, followed by addition of methyl acrylate (and hydrolysis of the product imine), gave the 2,2-disubstituted cyclohexanone 69 with high enantiomeric purity (1.78). 

Both reactions involve addition of organometaUic compounds to unsaturated carbonyl compounds. The key difference is the metal. With Cu(I) as catalyst, the Grignard reagent will give conjugate addition in the first case. MeLi will give direct addition in the second. 

Conjugate addition of organocuprates to , -unsaturated carbonyl compounds, including ketones, esters, and amides, are accelerated by addition of TMSCl to provide good yields of the 1,4-addition products (eq 31). The effect of additives such as HMPA, DMAP, and TMEDA have also been examined. The role of the TMSCl on 1,2- and 1,4-addition has been explored by several groups, and a recent report has been published by Lipshutz." His results appear to provide evidence that there is an interaction between the cuprate and TMSCl which influences the stereochemical outcome of these reactions. 

Michael Addition of -Keto Esters to Unsaturated Carbonyl Compounds. The conjugate addition of 18-keto esters to a. S-unsaturated ketones can be effected using 10 mol % copper(n) triflate immobilized in an ionic liquid ([BM1M][BF4]), as a recyclable catalytic system (eq 38). ... 

Scheme 3.28 General mechanism for conjugated addition of protic nucleophiles (NuH) to unsaturated carbonyl compounds...

Addition of dihydrosilane to a, /J-unsaturated carbonyl compounds such as citral (49), followed by hydrolysis, affords saturated citroneJlal (50) directly. The reaction is used for the selective reduction of conjugated double bonds[45,46]. In addition to Pd catalyst, the use of a catalytic amount of... 

CONJUGATE ADDITION OF ORGANOCOPPER REAGENTS TO a,p-UNSATURATED CARBONYL COMPOUNDS... 

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... 

Ammonia and amines undergo conjugate addition to a 3 unsaturated carbonyl compounds (Section 18 12) On the basis of this information predict the pnncipal organic product of each of the following reactions... 

Acrolein (H2C=CHCH=0) undergoes conjugate addition with sodium azide in aqueous solution to give N3CH2CH2CH=0 Propanal is not an a 3 unsaturated carbonyl compound and cannot undergo conjugate addition... 

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