Unsaturated carbonyl compounds addition

Addition of vinylic organometallic compounds to unsaturated carbonyl compounds addition of organometallic compounds to acetylenic carbonyl compounds... 

Modern aspects of electrophilic aromatic substitution chemistry address the development of enantioselective variants of these direct (hetero)arene functionalization reactions. For example, enantiomerically enriched metal catalysts, as well as organocatalysts, allowed for the asymmetric addition reactions of (hetero)arenes onto (a,P-unsaturated) carbonyl compounds. Additionally, highly enantioselective arylations of carbonyl compounds were accomplished with organometallic reagents... 

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. 

Aldol additions and ester condensations have always been and still are the most popular reactions for the formation of carbon-carbon bonds (A.T. Nielsen, 1968). The earbonyl group acts as an a -synthon, the enoi or enolate as a d -synthon. Both reactions will be treated together here, and arguments, which are given for aldol additions, are also valid for ester condensations. Many famous name reactions belong to this category ). The products of aldol additions may be either /J-hydroxy carbonyl compounds or, after dehydration, or, -unsaturated carbonyl compounds. 

The Michael reaction is of central importance here. This reaction is a vinylogous aldol addition, and most facts, which have been discussed in section 1.10, also apply here the reaction is catalyzed by acids and by bases, and it may be made regioselective by the choice of appropriate enol derivatives. Stereoselectivity is also observed in reactions with cyclic educts. An important difference to the aldol addition is, that the Michael addition is usually less prone to sterical hindrance. This is evidenced by the two examples given below, in which cyclic 1,3-diketones add to o, -unsaturated carbonyl compounds (K. Hiroi, 1975 H, Smith, 1964). 

Another widely used route to cyclopropanes involves the addition of sulfoniutn ylides to a,/3-unsaturated carbonyl compounds (S.R. Landor, 1967 R. Sowada, 1971 C.R. Johnson, I973B, 1979 B.M. Trost, 1975 A). Non-activated double bonds are not attacked. Sterical hindrance is of little importance in these reactions because the C—S bond is extraordinarily long... 

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... 

The diminished rr electron density m the double bond makes a p unsaturated aide hydes 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 p unsaturated carbonyl compounds than with simple alkenes... 

Ordinarily nucleophilic addition to the carbon-carbon double bond of an alkene is very rare It occurs with a p unsaturated carbonyl compounds because the carbanion that results IS an enolate which is more stable than a simple alkyl anion... 

CONJUGATE ADDITION OF ORGANOCOPPER REAGENTS 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... 

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... 

Methacryhc acid and its ester derivatives are Ctfjy -unsaturated carbonyl compounds and exhibit the reactivity typical of this class of compounds, ie, Michael and Michael-type conjugate addition reactions and a variety of cycloaddition and related reactions. Although less reactive than the corresponding acrylates as the result of the electron-donating effect and the steric hindrance of the a-methyl group, methacrylates readily undergo a wide variety of reactions and are valuable intermediates in many synthetic procedures. 

In the presence of suitable a,/5-unsaturated carbonyl compounds (3) the nucleophilic methylide (2) undergoes conjugate addition followed by expulsion of dimethyl sulfoxide to give cyclopropanes (5). 

Fluorinated a., -unsaturated carbonyl compounds also are reactive dipo-larophiles Because ol the highly activating carbonyl substituent, these 1,3-dipolar cycloadditions are rapid and regiospecific Good examples are the additions of... 

Conjugate addition (Sections 10.10 and 18.12) Addition reaction in which the reagent adds to the termini of the conjugated system with migration of the double bond synonymous with 1,4 addition. The most common examples include conjugate addition to 1,3-dienes and to a,(3-unsaturated carbonyl compounds. 

Subsequent to Hantzsch s communication for the construction of pyridine derivatives, a number of other groups have reported their efforts towards the synthesis of the pyridine heterocyclic framework. Initially, the protocol was modified by Beyer and later by Knoevenagel to allow preparation of unsymmetrical 1,4-dihydropyridines by condensation of an alkylidene or arylidene P-dicarbonyl compound with a P-amino-a,P-unsaturated carbonyl compound. Following these initial reports, additional modifications were communicated and since these other methods fall under the condensation approach, they will be presented as variations, although each of them has attained the status of named reaction . 

More recent work has shown that the 2-unsubstituted compound 40 (R = H, R = Pr ) is an effective formyl anion equivalent which reacts at C2 and undergoes both 1,4-addition to a,(3-unsaturated carbonyl compounds and 1,2-addition to aldehydes (93TL3907 96T4719). 

Michael addition reaction of 1-hydroxytryptamines to Q ,/3-unsaturated carbonyl compounds is worthy of note (99H2815). Addition of Ab-acetyl- 1-hydroxy-tryptamine (39) to methyl acrylate and methyl crotonate in the presence of... 

The addition of the a-carbon of an enolizable aldehyde or ketone 1 to the carbonyl group of a second aldehyde or ketone 2 is called the aldol reaction It is a versatile method for the formation of carbon-carbon bonds, and is frequently used in organic chemistry. The initial reaction product is a /3-hydroxy aldehyde (aldol) or /3-hydroxy ketone (ketol) 3. A subsequent dehydration step can follow, to yield an o ,/3-unsaturated carbonyl compound 4. In that case the entire process is also called aldol condensation. 

Especially with the ordinary aldol reaction a number of side reactions can be observed, as a result of the high reactivity of starting materials and products. For instance, the a ,/3-unsaturated carbonyl compounds 4 can undergo further aldol reactions by reacting as vinylogous components. In addition compounds 4 are potential substrates for the Michael reaction. 

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