Rate carbonylation

P carbon atom of an a 3 unsatu rated carbonyl compound is elec trophilic nucleophiles especially weakly basic ones yield the prod ucts of conjugate addition to a 3 unsaturated aldehydes and ketones... 

The principal synthetic application of lithium dialkylcuprate reagents IS their reaction with a 3 unsatu rated carbonyl compounds Al kylation of the 3 carbon occurs... 

Methyl group (Section 2 7) The group —CH3 Mevalonic acid (Section 26 10) An intermediate in the biosyn thesis of steroids from acetyl coenzyme A Micelle (Section 19 5) A sphencal aggregate of species such as carboxylate salts of fatty acids that contain a lipophilic end and a hydrophilic end Micelles containing 50-100 car boxylate salts of fatty acids are soaps Michael addition (Sections 18 13 and 21 9) The conjugate ad dition of a carbanion (usually an enolate) to an a 3 unsatu rated carbonyl compound... 

The Michael-type addition of maleic hydrazide and other pyridazinones to activated alkenes, such as methyl acrylate, acrylonitrile, methyl vinyl ketone and other a,/3-unsatu-rated carbonyl compounds, results in the formation of mono-lV-substituted products. 

Michael addition (Sections 18.13 and 21.9) The conjugate addition of a carbanion (usually an enolate) to an a,(3-unsatu-rated carbonyl compound. 

A diverse group of organic reactions catalyzed by montmorillonite has been described and some reviews on this subject have been published.19 Examples of those transformations include addition reactions, such as Michael addition of thiols to y./bunsatu rated carbonyl compounds 20 electrophilic aromatic substitutions,19c nucleophilic substitution of alcohols,21 acetal synthesis196 22 and deprotection,23 cyclizations,19b c isomerizations, and rearrangements.196 24... 

Tius and co-workers investigated a number of cationic cyclopentannelations of allenyl ethers [113] and found that 1-lithio-l-alkoxyallenes 180 react with a,/3-unsatu-rated carbonyl compounds 181 leading to highly functionalized cyclopentenones 182 (Scheme 8.44). The primary products are a-allenyl ketones 183, which form pentadienyl cations 184 by protonation. The latter undergo a thermally allowed 4jt-conrotatory ring closure to intermediates 185, which with elimination of R1 finally lead to the expected products 182 (Scheme 8.45). 

Fig. 10.24. Simplified metabolism of buta-1,3-diene (10.101), showing the formation of reactive metabolites bearing an epoxy group (i.e., 10.102, 10.103, and 10.105) or an a,(5-unsatu-rated carbonyl moiety (e.g., 10.109 and 10.110)...

Michael additions are conjugate 1,4-additions of enolates or amines to a,y9-unsatu-rated carbonyl compounds carried out under basic conditions. Up to now there are only a few examples for the solid-phase Michael addition (Scheme 3.17). 

Alkylidenation of aldehydes and cyclopropanation of o jS-unsatu-rated carbonyl compounds with dibromomalonic esters... 

Leaving precise mechanistic arguments aside, it should be stressed that an a,/9-unsatu-rated carbonyl compound can behave as a latent nucleophile with the assistance of a hydrosilane and a low-valence rhodium complex. With this simplification, isocyanates 18 and aldimines 20 were used as electrophiles for a similar protocol. Both were successfully incorporated with the aid of [Rh(COD)(P(OPh)3)2]OTf to afford 19 and 21, respectively (Scheme 6.5) in a reaction that was similar to the aldol-type coupling [11]. 

We have explored two types of carbon-carbon bond forming reactions operated under almost neutral conditions. Both reactions are initiated by the formation of an H-Rh-Si species through oxidative addition of a hydrosilane to a low-valence rhodium complex. Aldol-type three-component couphngs are followed by the insertion of an a,yS-unsatu-rated carbonyl compound into a Rh-H bond, whereas silylformylation is accomplished by the insertion of an acetylenic moiety into a Rh-Si bond. 

Hetero-Diels-Alder reaction with inverted electron demand between a, 3-unsatu-rated carbonyl compounds (1-oxa-l,3-butadienes 11 Scheme 6) and enol ethers provides an access to 6-alkoxy-3,4-dihydro-2/f-pyrans 12 [31,32]. These heterocycles are also useful... 

The product is an allylic alcohol. Which of the following methods might be considered for construction of an allylic alcohol aj addition of a vinyl Grignanf reagent to an aldehyde b) addition of an organometallic reagent to an a.p-unsaturated carbonyl compound or c) reduction of an a. p-unsatu rated carbonyl compound ... 

Synthesis of thietane-fused (1-lactam was reported by Sakamoto et al. [212] involving solid-state photoreaction of /V-(a,(5-unsatu rated carbonyl) thiobenzanilide demonstrating a single-step photochemical route to (5-lactam, as outlined in Scheme 52. 

Malonate anions react with the ri2-ethylene-Fe(CO)4 complex to afford after demetallation ethyl malonate derivatives. Reaction of nucleophiles with tetracar-bonyliron-activated c/.Jl-unsatu rated carbonyl compounds leads after protonation of the intermediate alkyl-Fe(CO)4 anions to the products of Michael addition. 

When methylene activation is provided by a nitrile group, 2-aminoM//-pyrans are formed (Equation 44) <2001T10163>. Likewise, malononitrile reacts with oi,[l-unsatu rated carbonyl systems to provide 2-amino-3-cyanoM//-pyrans (Equation 45) <2004SC1425>. Acrylonitrile derivatives also react with carbonyl activated methylene groups to afford 2-amino477-pyrj ns (Equation 46) <2003SC119>. 

According to Section 12.3 enamines are just one synthetic equivalent for enols that are not sufficiently represented in equilibrium with a carhonyl compound to allow for a-functional-izations. Enol ethers and silyl enol ethers, which are addressed in this section, are other synthetic equivalents for such enols. An enol ether, for example, is used as an enol equivalent for aldehyde enols, since several aldehydes do not form stable enamines. In addition, enol ethers or silyl enol ethers are usually employed as synthetic equivalents for the enols of ,/i-unsatu-rated carbonyl compounds. The attempt to react ce,/ -unsaturated carhonyl compounds with secondary amines to give a dienamine is often frustrated by a competing 1,4-addition of the amine. The combination of these factors turns the dienol ether B of Figure 12.23 into a species for which there is no analog in enamine chemistry. 

Of course, it is the goal of a crossed aldol condensation to produce a single ,/i-u nsatu-rated carbonyl compound. One has to keep in mind that crossed aldol condensations may result in up to four constitutionally isomeric condensation products (starting from two aldehydes or an aldehyde and a symmetric ketone) or even in eight constitutional isomers (starting with an aldehyde and an unsymetrical ketone). These maximum numbers of structural isomers result if both starting materials... 

The Michael reaction plays a part in some more extended synthetic sequences of great importance. Analyse TM11 6 as an a,P-unsatu-rated carbonyl compound and continue your... 

M. J. Chapdelaine and M. Hulce, Tandem vicinal difunctionalization /3-Addition to ,/3-unsatu-rated carbonyl substrates followed by a-functionalization, Org. React 1990, 38, 225-653. 

Bicyclic ketones are prepared by cycloadditions of methylenecyclopropanes with cyclic a,P-unsatu-rated carbonyl compounds. c J-Bicyclo[3.3.0]octan-2-ones (50), (51) and (52) are obtained in good yields by phosphine-nickel(0)-catalyzed cross coupling reactions of 2-cyclopentenone with methylenecyclopropanes in the presence of 0.1-1 equiv. of triethylborane as a Lewis acid (equations 18 and 19 and... 

For acyclic compounds the regioselectivity depends upon statistical factors and the relative acidities of the different 3-hydrogens, the elimination preferring to take place towards the most acidic hydrogen. This can also influence the regioselectivity of elimination from alicyclic compounds, e.g. the a,3-unsatu-rated carbonyl compound (14) was obtained from the 3-aminocarbonyl compound (13), and the allylic alcohol (16) was the major product obtained on oxidation and pyrolysis of the hydroxyamine (15). ... 

Common error alert a,fi-Unsaturated carbonyl compounds are not particularly acidic at the a-carbon atoms. The C=0 tt bond prefers to be in conjugation and coplanar with the C=C tt bond, so the C-H cr orbital does not overlap with the C=0 tt orbital. An unfavorable conformational change is required before deprotonation of the a-carbon can even begin. Note that the low acidity of a,(3-unsatu-rated carbonyl compounds as compared with their saturated congeners contradicts the general rule that C(sp2) is more acidic than C(sp3), all else being equal. 

Figure 28 Glutathione conjugation reactions of aromatic and OC, P-unsatu-rated carbonyl compounds, benzo[a]pyrene oxide, and ethacrynic acid, respectively.

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