Of a,0-unsaturated carbonyl compounds

The combined influences of polar and steric effects and of the strength of the newly formed bond93 was also recognized in the reaction of a,0-unsaturated carbonyl compounds and similar electron deficient alkenes95 with organomercurials and NaBH4. For the addition of alkyl radicals to substituted styrenes, p assumed a... 

Methylmagnesium N-cyclohexyliso-propylamide, 189 By oxidation at an allylic carbon Selenium dioxide, 272 By reduction of a,0-unsaturated carbonyl compounds Sodium borohydride, 278 Sodium dithionite, 281 Other methods r-Butyllithium, 58 Butyllithium-Potassium f-butoxide,... 

Selective hydrogenation of x,p-unsaturatedcarbonyl compounds. Japanese chemists1 have effected selective hydrogenation of a,0-unsaturated carbonyl compounds by a wine-red hydridoiron carbonyl complex generated in situ from iron pentacarbonyl and a small amount of base in moist solvents. Three different procedures can be used ... 

Overall yield of a,0-unsaturated carbonyl compound. "Hydrolytic workup with aqueous acid. Anhydrous isomerization with trifluoroacetic acid followed by hydrolytic work-up with aqueous acid. 

The Michael reaction occurs with a wide variety of a,0-unsaturated carbonyl compounds, not just conjugated enones. Unsaturated aldehydes, esters, nitriles, amides, and nitro compounds can all act as the electrophilic acceptor component in Michael reactions Table 23.1). Similarly, a variety... 

In Section 4, it is described that chlorotris(triphenylphosphine)rhodium(I) (7) is quite an effective catalyst for the hydrosilylation of carbonyl compounds. For this reason, extensive studies on asymmetric hydrosilylation of prochiral ketones to date have been based on employing rhodium(I) complexes with chiral phosphine ligands. The catalysts all prepared in situ are rhodium(I) complexes of the type, (BMPP>2Rh(S)a (8) [40] and (DIOP)Rh(S)Cl (6) [41], and a cationic rhodium(III) complex, [(BMPP)2lUiH2(S)2] Q04 (5) [42], where S represents a solvent molecule. An interesting polymer-supported rhodium complex (V) [41], and several chiral ferrocenylphosphines [43], recently developed as chiral ligands, have also been employed for asymmetric hydrosilylation of ketones. Included in this section also are selective asymmetric hydrosilylation of a,0-unsaturated carbonyl compounds and of certain keto esters. 

Steric factors are also important in hydrodimerizations carried out in acidic media. Excessive steric hindrance about the 0-carbon in an a, 0-unsaturated carbonyl compound can retard tail-to-tail coupling, e.g., 2 130 - 131, and lead to products of head-to-head (and occasionally head-to-tail) coupling. Thus in the reduction of mesityl oxide at pH lg.4 there is also formed a small amount of ketone 140, apparently formed via head-to-head coupling of 130 and subsequent pinacol rearrangement of 139 134) ... 

Considerable attention has been devoted to the preparation and chemistry of a,/3-unsaturated carbonyl compounds, which are valuable intermediates in organic synthesis [125]. Acid-promoted hydrolysis of alkoxyallenes has therefore frequently been employed to prepare a variety of functionalized a,/8-unsaturated carbonyl compounds [12b, 41, 44, 60, 126]. A recent example is illustrated in Scheme 8.54with C-l-silylated alkoxyallene 218 as a convenient starting material for the synthesis of bicyclo[5.4.0]undec-4-en-2-one 221. Sequential deprotonation and silylation at the terminal C=C bond efficiently transformed 218 into a 1,3-disilylated allene which was converted into the acryloylsilane 219 under acidic conditions. A [3 + 4] annula-tion of intermediate 219 with lithium dienolate 220 furnished bicydic compound 221 in good yield [127]. 

Kelly and colleagues91 explored the use of bisphenylenediol 103 as a catalyst in Diels-Alder reactions of a,/i-unsaturated carbonyl compounds. Activation of the dieno-phile occurred through double hydrogen bonding of the two hydroxyl functions on 103 to the carbonyl group on the dienophile. The reaction of cyclopentadiene with methyl vinyl ketone (equation 31) at ambient temperature showed, after a reaction time of 10 minutes, 3% of product formation in the absence of 103 against 90% of product formation in the presence of 0.4 equivalents of 103. 

Cyclopropanation of a,fi-unsaturated carbonyl compounds with dibromomalonates (typical procedure) To a mixture of diethyl dibromomalonate (0.95 g, 3 mmol) and methyl vinyl ketone (0.27 g, 3.1 mmol) is added dibutyl telluride (0.73 g, 3 mmol) under argon and with stirring. The exothermic reaction is completed within 1 h. The mixture is chromatographed on an AI2O3, column (70-230 mesh, elution with EtOAc), giving dibutyltellurium dibromide (1.01 g, 84%) and then l-acetyl-2,2-bis(ethoxycar-bonyl)cyclopropane, which is purified by Kiigelrohr distillation (0.59 g (86%) b.p. 88-90°C/0.08 torr). 

In general, LiBr and NEt3 are employed in 1.5 and 1.2 equiv, respectively. Although the reaction becomes rather slower, catalytic amounts of LiBr/NEt3 (0.1 equiv each) are also sufficient. In reactions with the highly reactive dipolarophile N-methylmaleimide, the catalytic reaction results in a better yield. A similar lithiation is possible with a-substituted (alkylideneamino)acetates and (alkylideneamino)-acetamides to generate lithium enolates (86). Cycloadditions with a variety of a,(3-unsaturated carbonyl compounds leads to endo cycloadducts. However, the reaction with acrylonitrile is again nonstereoselective. 

Amines, thiols, eOH (p. 226), etc., will also add to the (3-carbon atom of a(l-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 ... 

The effect of conjugation also is reflected in infrared carbonyl frequencies (Section 16-3A) and nmr spectra. With respect to the latter, it is found that the protons on the (3 carbon of a,/3-unsaturated carbonyl compounds usually come at 0.7 to 1.7 ppm lower fields than ordinary alkenic protons. The effect is smaller for the a protons. 

Hydrocarbons 407 can be used as precursors in hydroxyalkylation reactions of a,p-unsaturated carbonyl compounds 408 in the presence of molecular oxygen (Fig. 95) [438]. The reactions are catalyzed by 0.3-1 mol% Co(acac)3 and 30 mol% 398. Alkylated a-hydroxy carbonyl compounds 409 and a-keto carbonyl compounds 410 were obtained in 42-98% yield in a 1-100 1 ratio. The reactions showed a considerable induction period. Co(acac)2, in contrast, initiated the reaction very quickly, but conversion soon ceased. The success using the unreactive Co(III) complex consists of gradual reduction to catalytically active Co(II). 

Compounds with double bonds adjacent to a C=0 group are known as a,p-unsaturated carbonyl compounds. Many a,[3-unsaturated carbonyl compounds have trivial names, and some are shown here. Some classes of a, 3-unsaturated carbonyl compounds also have names such as enone or enal , made up of lene (for the double bond) + one (for ketone) or ene + al (for aldehyde). 

Addition reactions. a,0-Unsaturated carbonyl compounds 1 and 3 undergo exclusive 1,4-addition reactions with organolithium (and organomagnesium) compounds owing to steric hindrance of the carbonyl group. The adducts 2 and 4 are converted into carboxylic acids by cleavage with potassium t-butoxide and H2O in the case of 2 see potassium r-hutoxidc, this volume) and by treatment with ethanolic... 

Furthermore, several syntheses of a,p-unsaturated carbonyl compounds have involved the alkylation of suitably functionalized sulfones, followed by the base-promoted elimination of the sulfenate moiety on related alkyl sulfones bearing an oxygen atom at the -y-position (Scheme 106, entries b-d Scheme 110, entry c Scheme 105, entry b). - 46i Particularly interesting is the synthesis of nuciferal (Scheme 106, entry d) which involves sequential alkylation of y,-y-dioxy sulfones, deblocking of the acetal moiety and sulfenate elimination. In this and related reactions y, y-dioxy-a-metalloalkyl sulfone has played the role of a masked p-metallo-a,p-unsaturated carbonyl compound (M(>aC—C—C=0), which is not a directly available synthon. 

LKnoevenagel Reaction. Aldehydes and ketones frequently react with tive methylene compounds such as acetoacetic ester, malonic ester, and cyanoacetic ester to form a,0-unsaturated carbonyl compounds. This reaction usually is called the Knoevcnagel reaction. As has been said, the process appears to proceed best in the presence of ammonia derivatives and acetic acid.15 The reaction can be illustrated with the... 

Reduction of a,[3-unsaturated carbonyl compounds [105] A solution of the carbonyl compound 36 (1.0 mmol) in methanol (20 mL) was added to the resin (0.5 g, 1.25 mmol). After completion of the reaction, the resin was fil-... 

Azran, J., 0. Buchman, I. Amer, and J. Blum, Selective Hydrogenation of a, 8-Unsaturated Carbonyl Compounds by Rhodium Trichloride and Aliquat 336 in a Two-Phase Liquid System,7. MoL CataL, 34, 229 (1986). 

Since the resulting silyl enol ethers and allylic silyl ethers can readily be converted by hydrolysis to saturated carbonyl compounds and allylic alcohols, respectively, these reactions furnish a unique method for the selective reduction of a,0-unsaturated carbonyl compounds125,126,128. a,0-Unsaturated carbonyl compounds containing an isolated double bond in the same molecule also undergo the selective reduction without isomerization or reduction at the isolated double bond125,126,128 (see, e.g., equations 68 and 69). 

Figure 4. A. Synthesis of enamino carbonyl derivatives from 1,3-dicarbonyl compounds and amines [51], B. Reaction of furan with a,/0-unsaturated carbonyl compounds [52].

The case of a,6-unsaturated carbonyl compounds is analogous to that of 1,3-dienes, in that conjugation favors coplanarity of the C=C—C=0 system. The rotamers that are important are the s-trans and s-cis conformations. Microwave data indicate that the s-trans form is the only conformation present in detectable amounts in 2-propenal (acrolein). ... 

Catalytic hydrogenation of a,fi-unsaturated carbonyl compounds. a,0-Unsaturated aldehydes and ketones are reduced to the corresponding saturated carbonyl compounds with high selectivity under conditions of the oxo reaction [H2,CO,Co2(CO)a, 1,225-226]. ... 

Hetero Diels-Alder cycloaddition of a,p-unsaturated carbonyl compounds and dioxygenated alkenes in the presence of a chiral bisoxazoline-Cu(OTf)2 complex as Lewis add catalyst furnished hexopyranose precursors in good yields and high enantomeric excess. In the synthesis of the precursor 6 of ethyl tetra-0-acetyl-P-D-mannopyranose outlined in Scheme 1, for example, a 69% overall yield and 99% ee were achieved. A new route to hex-2-uloses involving boron-or, preferably, lithium-enolates is exemplified in Scheme 2. Only 3,4-trans-... 

This reaction can be used to prepare different phenols (e.g., via the oxidation of ben-zaldehydes or phenyl ketones), enol esters (from a,)0-unsaturated carbonyl compounds) and aldehydes (from the further hydrolysis of corresponding enol esters). 

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