Conjugate carbonyl addition mechanism

Coniine, molecular model of. 28 structure of, 294 Conjugate acid, 49 Conjugate base, 49 Conjugate carbonyl addition reaction, 725-729 amines and, 727 enamines and, 897-898 Gilman reagents and, 728-729 mechanism of, 725-726 Michael reactions and, 894-895 water and. 727 Conjugated diene, 482... 

However, the ready distortion of the ar-electron system provides an additional mechanism whereby the charge dispersal can reach the substituents. The greater substituent effects in ketones compared to the alcohols are therefore equally consistent with the loss of an oxygen nonbonding electron. Unsaturated substituents which can conjugate with the carbonyl double bond do not have the expected large effect in reducing... 

HCN also adds to alkenes in the presence of an appropriate catalyst (Arthur et al., 1954 Jackson and Level, 1982). Thus, cobalt carbonyl leads to Markownikov addition, for example, 1-propene yields isopropyl cyanide in approximately 75% yield. HCN adds to alkynes in the presence of metal complexes, and the use of a nickel complex may lead to syn addition (Jackson and Level, 1983 Jackson et al., 1988). Hydrogen cyanide reacts with conjugated dienes, the mechanism involving a TT-allyl intermediate. The course of addition is complex and may lead to more than one product (Keim et al., 1982). 

In this section, we ll take a break from our survey of reaction mechanisms and focus instead on a class of intermediates, namely, carbanions. We will also discuss carbanion cognates such as enols, enolates, enamines, and ylides. As classic nucleophiles, carbanions react in highly characteristic ways, particularly via 8 2 displacements, as well as via other pathways (e.g., carbonyl addition and conjugate addition) we have discussed above. The material in this section will thus help you flesh out your understanding of what we have discussed so far. 

The mechanism of a Dieckmann condensation is identical to the mechanism we described for the Claisen condensation. An anion formed at the a-carbon of one ester in Step 1 adds to the carbonyl of the other ester group in Step 2 to form a tetrahedral carbonyl addition intermediate. This intermediate ejects ethoxide ion in Step 3 to regenerate the carbonyl group. Cyclization is followed by formation of the conjugate base of the j8-ketoester in Step 4, just as in the Claisen condensation. The j8-ketoester is isolated after acidification with aqueous acid. 

We now show how the conjugated carbonyl group of a,j8-unsaturated aldehydes and ketones can enter into reactions that involve the entire functional system. These reactions are 1,4-additions of the type encountered with conjugated dienes, such as 1,3-butadiene (Section 14-6). The reactions proceed by acid-catalyzed, radical, or nucleophilic addition mechanisms, depending on the reagents. 

The mechanism of conjugate addition reactions probably involves an initial complex between the cuprate and enone.51 The key intermediate for formation of the new carbon-carbon bond is an adduct formed between the enone and the organocopper reagent. The adduct is formulated as a Cu(III) species, which then undergoes reductive elimination. The lithium ion also plays a key role, presumably by Lewis acid coordination at the carbonyl oxygen.52 Solvent molecules also affect the reactivity of the complex.53 The mechanism can be outlined as occurring in three steps. 

In an extension of previous work on conjugated enamine carbonyl derivatives, reaction of the pyrazolone 91 with IV.lV-disubstituted hydrazines on heating in an alcohol solvent afforded the hexahydropyrazolo[4,3-Michael-type addition of the alcohol to a pre-formed pyrazolo-diazepine, was excluded <06T8126>. 

While a large number of studies have been reported for conjugate addition and Sn2 alkylation reactions, the mechanisms of many important organocopper-promoted reactions have not been discussed. These include substitution on sp carbons, acylation with acyl halides [168], additions to carbonyl compounds, oxidative couplings [169], nucleophilic opening of electrophilic cyclopropanes [170], and the Kocienski reaction [171]. The chemistry of organocopper(II) species has rarely been studied experimentally [172-174], nor theoretically, save for some trapping experiments on the reaction of alkyl radicals with Cu(I) species in aqueous solution [175]. 

The Michael reaction involves conjugate addition of a nucleophile onto an a,P-unsaturated carbonyl compound, or similar system. Such reactions take place in nature as well, and some can be potentially dangerous to us. For example, the a,P-unsaturated ester ethyl acrylate is a cancer suspect agent. This electrophile can react with biological nucleophiles and, in so doing, bind irreversibly to the nucleophile, rendering it unable to carry out its normal functions. A particularly important enzyme that can act as a nucleophile is DNA polymerase, which is responsible for the synthesis of strands of DNA, especially as part of a DNA repair mechanism (see Section 14.2.2). The nucleophilic centre is a thiol grouping, and this may react with ethyl acrylate as shown. 

In general, the reactions in the addition phase of both the base- and acid-catalyzed mechanisms are reversible. The equilibrium constant for addition is usually unfavorable for acyclic ketones. The equilibrium constant for the dehydration phase is usually favorable, because of the conjugated a,/ -unsaturated carbonyl system that is formed. When the reaction conditions are sufficiently vigorous to cause dehydration, the overall reaction will go to completion, even if the equilibrium constant for the addition step is unfavorable. Entry 3 in Scheme 2.1 illustrates a clever way of overcoming the unfavorable equilibrium of the addition step. The basic catalyst is contained in a separate compartment of a Soxhlet extractor. Acetone is repeatedly passed over the basic catalyst by distillation and then returns to the reaction flask. The concentration of the addition product builds up in the reaction flask as the more volatile acetone distills preferentially. Because there is no catalyst in the reaction flask, the adduct remains stable. 

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