Carbonyl compounds addition-elimination

Contrary to some reports, electrophilic addition reactions may occur in other multiple-bond systems. In many of the reactions of aldehydes and ketones the first stage involves the addition of some entity across the carbon-oxygen bond, e.g., the formation of oximes, semicarbazones, hydrazones, hydrates (1,1-diols) and their ethers, and the aldol condensation. Most of these reactions entail a subsequent loss (elimination) of a small molecule e.g. water, ammonia, ethanol) and, while one must be careful to determine whether the rate-determining stage involves attack on the carbonyl compound or elimination from the adduct , there are some systems in which it is evident that electrophilic attack is involved in the slow stage of the reaction sequence. Examples of such reactions are the acid-catalysed formation of oximes of aliphatic - and aromatic carbonyl compounds, of furfural semi-carbazone , and of 1,1-diols from aldehydes or ketones . 

The radical addition of sulfinates to unsaturated compounds via the iodosulfonylation-dehydroiodination reaction sequence constitutes a general method for the preparation of vinyl sulfones the latter may be rearranged to aUyUc sulfones by treatment with base. The radical addition may be carried out on a, -unsaturated carbonyl compounds as well as alkenes. In the case of unsaturated carbonyl compounds the elimination process can be quite stereoselective, ( )-alkenes being normally formed. For the addition to nonconjugated alkenes, conditions have been described for the preparation of either ( )- or (. -alkenes. ... 

The Baylis-Hillman reaction is generally defined as a base-catalyzed reaction between an a,P-unsaturated carbonyl compound and an aldehyde. However, the experimental evidence clearly demonstrates that the catalyst is involved in the reaction as a nucleophile, not as a hase. The steps of the process include the conjugate addition of the catalyst to the a,p-unsaturated carbonyl compound, addition to the aldehyde, and elimination. The reaction has a very high volume of activation and the rate is very sensitive to an increase in pressure. 

The Julia-Lythgoc olefination operates by addition of alkyl sulfone anions to carbonyl compounds and subsequent reductive deoxysulfonation (P. Kocienski, 1985). In comparison with the Wittig reaction, it has several advantages sulfones are often more readily available than phosphorus ylides, and it was often successful when the Wittig olefination failed. The elimination step yields exclusively or predominantly the more stable trans olefin stereoisomer. 

The use of a reagent bearing a basic center or the addition of a base to the reaction mixture was recognized as necessary to prevent the acid-catalyzed elimination of the elements of water from the intermediates. Since the publication of this work, a number of similar intermediates have been isolated from thioamides and a-halogeno carbonyl compounds (608, 609, 619, 739, 754, 801), and as a result of kinetic studies, the exact mechanism of this reaction has been well established (739, 821). 

A number of compounds of the general type H2NZ react with aldehydes and ketones m a manner analogous to that of primary amines The carbonyl group (C=0) IS converted to C=NZ and a molecule of water is formed Table 17 4 presents exam pies of some of these reactions The mechanism by which each proceeds is similar to the nucleophilic addition-elimination mechanism described for the reaction of primary amines with aldehydes and ketones... 

The mechanistic pattern established by study of hydration and alcohol addition reactions of ketones and aldehydes is followed in a number of other reactions of carbonyl compounds. Reactions at carbonyl centers usually involve a series of addition and elimination steps proceeding through tetrahedral intermediates. These steps can be either acid-catalyzed or base-catalyzed. The rate and products of the reaction are determined by the reactivity of these tetrahedral intermediates. 

Upon addition of a base—triethylamine is often used—the sulfonium salt 7 is deprotonated to give a sulfonium ylide 8. The latter decomposes into the carbonyl compound 2 and dimethyl sulfide 9 through /3-elimination via a cyclic transition state. 

As a general rule, nucleophilic addition reactions are characteristic only of aldehydes and ketones, not of carboxylic acid derivatives. The reason for the difference is structural. As discussed previously in A Preview of Carbonyl Compounds and shown in Figure 19.14, the tetrahedral intermediate produced by addition of a nucleophile to a carboxylic acid derivative can eliminate a leaving group, leading to a net nucleophilic acyl substitution reaction. The tetrahedral intermediate... 

Acyloins (a-hydroxy ketones) are formed enzymatically by a mechanism similar to the classical benzoin condensation. The enzymes that can catalyze reactions of this type arc thiamine dependent. In this sense, the cofactor thiamine pyrophosphate may be regarded as a natural- equivalent of the cyanide catalyst needed for the umpolung step in benzoin condensations. Thus, a suitable carbonyl compound (a -synthon) reacts with thiamine pyrophosphate to form an enzyme-substrate complex that subsequently cleaves to the corresponding a-carbanion (d1-synthon). The latter adds to a carbonyl group resulting in an a-hydroxy ketone after elimination of thiamine pyrophosphate. Stereoselectivity of the addition step (i.e., addition to the Stand Re-face of the carbonyl group, respectively) is achieved by adjustment of a preferred active center conformation. A detailed discussion of the mechanisms involved in thiamine-dependent enzymes, as well as a comparison of the structural similarities, is found in references 1 -4. 

In the presence of a catalytic amount of triethylamine, a readily enolizable carbonyl compound like acetylacetone (25) can undergo a Michael-type addition onto the triple bond of 23 with C-C bond formation, and subsequent 1,2-addition of the hydroxy group with elimination of an alcohol (MeOH or EtOH) to eventually yield a pyranylidene complex 28 (mode E) [29]. The most versatile access to / -donor-substituted ethenylcarbene complexes 27 is by Michael-type additions of nucleophiles, including alcohols [30-32], primary... 

The Julia olefination involves the addition of a sulfonyl-stabilized carbanion to a carbonyl compound, followed by elimination to form an alkene.277 In the initial versions of the reaction, the elimination was done under reductive conditions. More recently, a modified version that avoids this step was developed. The former version is sometimes referred to as the Julia-Lythgoe olefination, whereas the latter is called the Julia-Kocienski olefination. In the reductive variant, the adduct is usually acylated and then treated with a reducing agent, such as sodium amalgam or samarium diiodide.278... 

These reactions involve addition of the diazo ester to an adduct of the carbonyl compound and the Lewis acid. Elimination of nitrogen then triggers migration. Triethyloxonium tetrafluoroborate also effects ring expansion of cyclic ketones by ethyl diazoacetate.83... 

In the reduction of acids there is a tendency for the lithium salt, RCO20Li to separate from the ethereal solution, and thus bring reduction to a halt this can be avoided by first converting the acid to a simple, e.g. Me or Et, ester. In the reduction of the latter, the initial nucleophilic attack by AIH4 results in an addition/elimination reaction—OR is a good leaving group in (40)—followed by normal attack, as above, on the resultant carbonyl compound (41) to yield the primary alcohol (42) ... 

The mechanism of this transformation is a matter of debate, and may vary with the structure of the heteroanalogous carbonyl compound employed. Although a Diels-Alder-type process is conceivable [246], a Lewis acid-induced addition of the silyl enol ether moiety in 2-453 followed by a cyclizahon through a nucleophilic intramolecular attack of the amine and subsequent elimination of methanol is assumed in this case [247]. 

Ballini and coworkers have developed a new strategy for alkenylation of carbonyl compounds based on the Michael addition followed by elimination of HN02 (see Section 7.3). A variety of 2-alkylidene 1,4-dioles have been conveniently prepared, in two steps, by the Michael addition of a nitroalkane to the appropriate enedione derivatives under basic conditions, followed by chemoselective reduction with LiAlH4 (Eq. 4.123).170... 

These reactions comprise nucleophilic SN2 substitutions, -eliminations, and nucleophilic additions to carbonyl compounds or activated double bonds, etc. They involve the reactivity of anionic species Nu associated with counterions M+ to form ion-pairs with several possible structures [52] (Scheme 3.4). 

Zard and coworkers have developed a synthesis of substituted dienes by reductive elimination of allylic nitroacetates (equation 33)66. Allylic nitroacetates can be prepared by condensation of nitromethane with the carbonyl compound followed by addition of formaldehyde and acetylation67. Reductive elimination can be carried out by employing either chromous acetate or samarium iodide. 

The Peterson olefination reaction involves the addition of an a-silyl substituted anion to an aldehyde or a ketone followed by the elimination of silylcarbinol either under acidic (awP -elimination) or basic (syn-elimination) conditions to furnish olefins178. Thus, Peterson olefination, just like Wittig and related reactions, is a method for regioselective conversion of a carbonyl compound to an olefin. Dienes and polyenes can be generated when the Peterson reaction is conducted using either an ,/l-unsaturated carbonyl compound or unsaturated silyl derivatives as reaction partners (Table 20)179. 

Figure 6.21 Addition-elimination of dialkyl phosphite salts with a,P-unsaturated carbonyl compounds.

Rhodium(i) complexes are excellent catalysts for the 1,4-addition of aryl- or 1-alkenylboron, -silicon, and -tin compounds to a,/3-unsaturated carbonyl compounds. In contrast, there are few reports on the palladium(n) complex-catalyzed 1,4-addition to enones126,126a for the easy formation of C-bound enolate, which will result in /3-hydride elimination product of Heck reaction. Previously, Cacchi et al. described the palladium(n)-catalyzed Michael addition of ArHgCl or SnAr4 to enones in acidic water.127 Recently, Miyaura and co-workers reported the 1,4-addition of arylboronic acids and boroxines to a,/3-unsaturated carbonyl compounds. A cationic palladium(n) complex [Pd(dppe)(PhCN)2](SbF6)2 was found to be an excellent catalyst for this reaction (dppe = l,2-bis(diphenyl-phosphine)ethane Scheme 42).128... 

Although detailed mechanistic studies are not reported, the postulated mechanism for the reductive cyclization of allenic carbonyl compounds involves entry into the catalytic cycle via silane oxidative addition. Allene silylrhodation then provides the cr-allylrhodium hydride A-18, which upon carbometallation of the appendant aldehyde gives rise to rhodium alkoxide B-14. Oxygen-hydrogen reductive elimination furnishes the hydrosilylation-cyclization product... 

Since nucleophilic addition to a metal-coordinated alkene generates a cr-metal species bonded to an -hybridized carbon, facile 3-H elimination may then ensue. An important example of pertinence to this mechanism is the Wacker reaction, in which alkenes are converted into carbonyl compounds by the oxidative addition of water (Equation (108)), typically in the presence of a Pd(n) catalyst and a stoichiometric reoxidant.399 When an alcohol is employed as the nucleophile instead, the reaction produces a vinyl or allylic ether as the product, thus accomplishing an etherification process. 

Michael additions occur between (diethoxyvinylidene)triphenylphosphorane and carbonyl compounds which have an a-CHa. The initial products eliminate EtOH to... 

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