Bonds unsaturated carbonyl compounds

Analysis Another lactone FGl reveals the true TM (A). Our normal discormection a of an a,p-unsaturated carbonyl compound gives us the 1,5-dicarbonyl compound (B) and the ketone (C) clearly derived from phenol. Alternatively we could disconnect bond b to the keto-ester (D) with the further discormection shown ... 

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. 

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... 

Triethylammonium formate is another reducing agent for q, /3-unsaturated carbonyl compounds. Pd on carbon is better catalyst than Pd-phosphine complex, and citral (49) is reduced to citronellal (50) smoothly[55]. However, the trisubstituted butenolide 60 is reduced to the saturated lactone with potassium formate using Pd(OAc)2. Triethylammonium formate is not effective. Enones are also reduced with potassium formate[56]. Sodium hypophosphite (61) is used for the reduction of double bonds catalyzed by Pd on charcoal[57]. 

The carbonyl group withdraws rr electron density from the double bond and both the carbonyl carbon and the p carbon are positively polarized Their greater degree of charge separation makes the dipole moments of a p unsaturated carbonyl compounds signifi cantly larger than those of comparable aldehydes and ketones... 

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 (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. 

One of the most important routes to isoxazole and isoxazoline rings involving the formation of the 1—5 and 2—3 bonds involves the condensation of hydroxylamine with a,/8-unsaturated carbonyl compounds. This method was previously widely used, but it is now of no preparative value, though it has been recently applied to determine the configuration of oximes. " The only new modification of this synthesis is the use of the acetals (27) of a,/8-acetylenic aldehydes for preparation of 5-substituted isoxazoles (28)... 

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. 

The 1,4-addition of an enolate anion 1 to an o ,/3-unsaturated carbonyl compound 2, to yield a 1,5-dicarbonyl compound 3, is a powerful method for the formation of carbon-carbon bonds, and is called the Michael reaction or Michael addition The 1,4-addition to an o ,/3-unsaturated carbonyl substrate is also called a conjugate addition. Various other 1,4-additions are known, and sometimes referred to as Michael-like additions. 

The overall process is the addition of a CH-acidic compound to the carbon-carbon double bond of an o ,/3-unsaturated carbonyl compound. The Michael reaction is of particular importance in organic synthesis for the construction of the carbon skeleton. The above CH-acidic compounds usually do not add to ordinary carbon-carbon double bonds. Another and even more versatile method for carbon-carbon bond formation that employs enolates as reactive species is the aldol reaction. 

Strategy The overall result of an enamine reaction is the Michael addition of a ketone as donor to an cr,/3-unsaturated carbonyl compound as acceptor, yielding a 1,5-dicarbonyl product. The C—C bond made in the Michael addition step is the one between the a- carbon of the ketone donor and the /3 carbon of the unsaturated acceptor. 

An alternative strategy for promoting Diels-Alder reaction by proton involves the activation of dienophile by hydrogen bonding [93]. Biphenylene diol 143 (Scheme 4.26) forms doubly hydrogen-bonded complexes with a,j]-unsaturated carbonyl compounds, which strongly accelerate the Diels-Alder... 

A part of the mechanistic spectrum is supported by the [2+2] cycloaddition reactions between the unsaturated carbon bonds and carbonyl compounds [24]. 

Four-membered ring formation between unsaturated carbon bonds and carbonyl compounds is a photochemical reaction [25], This is an excited-state reaction in the delocalization band (Scheme 6). 

The enantioselective 1,4-addition addition of organometaUic reagents to a,p-unsaturated carbonyl compounds, the so-called Michael reaction, provides a powerful method for the synthesis of optically active compounds by carbon-carbon bond formation [129]. Therefore, symmetrical and unsymmetrical MiniPHOS phosphines were used for in situ preparation of copper-catalysts, and employed in an optimization study on Cu(I)-catalyzed Michael reactions of di-ethylzinc to a, -unsaturated ketones (Scheme 31) [29,30]. In most cases, complete conversion and good enantioselectivity were obtained and no 1,2-addition product was detected, showing complete regioselectivity. Of interest, the enantioselectivity observed using Cu(I) directly in place of Cu(II) allowed enhanced enantioselectivity, implying that the chiral environment of the Cu(I) complex produced by in situ reduction of Cu(II) may be less selective than the one with preformed Cu(I). 

Phosphides add to the double bond of j8-unsaturated carbonyl compounds to give the phosphines (13). 

A second important reaction type considered in this chapter is conjugate addition, which involves addition of nucleophiles to electrophilic double or triple bonds. A crucial requirement for this reaction is an electron-withdrawing group (EWG) that can stabilize the negative charge on the intermediate. We focus on reactions between enolates and a,(3-unsaturated carbonyl compounds and other electrophilic alkenes such as nitroalkenes. 

Among the olefination reactions, those of phosphonium ylides, phosphonate anions, silylmethyl anions, and sulfone anions are discussed. This chapter also includes a section on conjugate addition of carbon nucleophiles to a, (J-unsaturated carbonyl compounds. The reactions in this chapter are among the most important and general of the carbon-carbon bond-forming reactions. 

When the conditions are controlled properly, Zn can mediate the reduction of the C-C double bond of a, (3-unsaturated carbonyl compounds in the presence of a nickel catalyst in aqueous ammonium chloride (Eq. 10.7). The use of ultrasonication enhances the rate of the reaction.15 Sodium hydrogen telluride, (NaTeH), prepared in situ from the reaction of... 

Amines, thiols, eOH (p. 226), etc., will also add to the 0-carbon atom of 0-unsaturated carbonyl compounds and esters, but the most important reactions of C=C—C=0 systems are in Michael reactions with carbanions reactions in which carbon-carbon bonds are formed. A good example is the synthesis of l,l-dimethylcyclohexan-3,5-dione (dimedone, 100) starting from 2-methylpent-2-ene-4-one (mesityl oxide, 101) and the carbanion 0CH(CO2Et)2 ... 

Complexes 17-19 can be written in one valence structure as a, /3-unsaturated carbonyl compounds in which the carbonyl oxygen atom is coordinated to a BF2(OR) Lewis acid. The C=C double bonds of such organic systems are activated toward certain reactions, like Diels-Alder additions, and complexes 17-19 show similar chemistry. Complexes 17 and 18 undergo Diels-Alder additions with isoprene, 2,3-dimethyl-1,3-butadiene, tram-2-methyl-l,3-pentadiene, and cyclopentadiene to give Diels-Alder products 20-23 as shown in Scheme 1 for complex 17 (32). Compounds 20-23 are prepared in crude product yields of 75-98% and are isolated as analytically pure solids in yields of 16-66%. The X-ray structure of the isoprene product 20 has been determined and the ORTEP diagram (shown in Fig. 3) reveals the regiochemistry of the Diels-Alder addition. The C-14=C-15 double bond distance is 1.327(4) A, and the... 

When the electron demand of a,p-unsaturated carbonyl compounds is weakened by additional substituents in P-position, the double bond returns to normal behavior as far as cyclopropanation is concerned. Some recent examples, displayed in Scheme 21, may illustrate this point. 

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