Carbonyl compounds with alkenes

Cycloaddition Reactions of Fluorinated Alkenes with Carbonyl Compounds... 

Reaction of alkenes with carbonyl compounds or carbonyl derivatives in the presence of Lewis acids, the ene reaction, enables the stereoselective preparation of highly functionalized compounds. Copper Lewis acids activate both aldehydes and imines in ene reactions. Evans has reported that Cu(II) Lewis acids catalyze glyoxylates in reactions with alkenes (Sch. 56) [103]. The homoallylic alcohols 257 and 259 are produced in high yield and enantioselectivity. The bis aquo complex 260 is a readily prepared and air-stable catalyst and gave high chemical yield and excellent selectivity in the ene reactions. Another point of note is that catalysts 260 and 261 furnish enantiomeric products even though they differ from each other only by the substituent at the 4-posi-tion of the oxazoline. 

The reaction types permitted by photochemical excitation that are particularly useful for synthesis are 2 + 2 additions between two carbon-carbon double bonds, and 2 + 2 addition of alkenes with carbonyl compounds leading to oxetanes. Many... 

Allylboron compounds have proven to be an exceedingly useful class of allylmetal reagents for the stereoselective synthesis of homoallylic alcohols via reactions with carbonyl compounds, especially aldehydes1. The reactions of allylboron compounds and aldehydes proceed by way of cyclic transition states with predictable transmission of olefinic stereochemistry to anti (from L-alkene precursors) or syn (from Z-alkene precursors) relationships about the newly formed carbon-carbon bond. This stereochemical feature, classified as simple diastereoselection, is general for Type I allylorganometallicslb. 

Trialkylsilyl groups have a modest stabilizing effect on adjacent carbanions (see Part A, Section 3.4.2). Reaction of the carbanions with carbonyl compounds gives (3-hydroxyalkylsilanes. (3-Hydroxyalkylsilanes are converted to alkenes by either acid or base.270 These eliminations provide the basis for a synthesis of alkenes. The reaction is sometimes called the Peterson reaction.211 For example, the Grignard reagent derived from chloromethyltrimethylsilane adds to an aldehyde or ketone and the intermediate can be converted to a terminal alkene by acid or base.272... 

Whereas phosphonium ylides normally react with carbonyl compounds to give alkenes, dimethylsulfonium methylide and dimethylsulfoxonium methylide yield epoxides. Instead of a four-center elimination, the adducts from the sulfur ylides undergo intramolecular displacement of the sulfur substituent by oxygen. In this reaction, the sulfur substituent serves both to promote anion formation and as the leaving group. 

Phosphonothiazolylmethanes 40 react with carbonyl compounds to give the expected alkene products via Knoevenagel or Homer-Wadsworth Emmons reactions. When they are treated with oc-haloketones, pyrrolothiazoles 42 are obtained in a two stage process via the quaternary salt 41 <98PSS251>. 

The reactions of allylmetal reagents with carbonyl compounds and imines have been extensively investigated during the last two decades [1], These carbon—carbon bondforming reactions possess an important potential for controlling the stereochemistry in acyclic systems. Allylmetal reagents react with aldehydes and ketones to afford homo-allylic alcohols (Scheme 13.1), which are valuable synthetic intermediates. In particular, the reaction offers a complementary approach to the stereocontrolled aldol process, since the newly formed alkenes may be readily transformed into aldehydes and the operation repeated. 

Allyltitanium complexes derived from a chiral acetal have been reacted with carbonyl compounds and imines [63], While the chiral induction proved to be low with carbonyl compounds, high induction was observed with imines. This complex represents the first chiral homoenolate equivalent that reacts efficiently with imines. Finally, the reactions with electrophiles other than carbonyl compounds and imines, namely a proton source, NCS, and I2, furnished the corresponding alkene, chloro, and iodo derivatives in good yields [64]. 

Cycloreversion of four-membered metallacycles is the most common method for the preparation of high-valent titanium [26,27,31,407,599-606] and zirconium [599,601] carbene complexes. These are usually very reactive, nucleophilic carbene complexes, with a strong tendency to undergo C-H insertion reactions or [2 -F 2] cycloadditions to alkenes or carbonyl compounds (see Section 3.2.3). Figure 3.31 shows examples of the generation of titanium and zirconium carbene complexes by [2 + 2] cycloreversion. 

As discussed in previous sections, high-valent carbene complexes of early transition metals have ylide-like, nucleophilic character. Some Schrock-type carbene complexes react with carbonyl compounds in the same manner as do phosphorus ylides, namely by converting the carbonyl group into an alkene. 

Interestingly, sulfonium ylides generated from electrophilic carbene complexes and sulfides can react with carbonyl compounds, imines, or acceptor-substituted alkenes to yield oxiranes [1320-1325], aziridines [1321,1326,1327] or cyclopropanes [1328,1329], respectively. In all these transformations the thioether used to form the sulfonium ylide is regenerated and so, catalytic amounts of thioether can be sufficient for complete conversion of a given carbene precursor into the... 

An important complement to the Wittig reaction is the reaction of phosphonate carbanions with carbonyl compounds.151 The alkylphosphonate esters are made by the reaction of an alkyl halide, preferably primary, with a phosphite ester. Phosphonate carbanions are more nucleophilic than an analogous ylide, and even when R is a carbanion-stabilizing substituent, they react readily with aldehydes and ketones to give alkenes. Phosphonate carbanions are generated by treating alkylphosphonate esters with bases such as sodium hydride, w-butyllithium, or sodium ethoxide. Alumina coated with KF or KOH has also found use as the base.152... 

Alkylation with Carbonyl Compounds The Prins Reaction. Carbonyl compounds react with alkenes in the presence of Brpnsted acids to form a complex mixture of products known as the Prins reaction. The use of appropriate reaction conditions, solvents, and catalysts allows one to perform selective syntheses. Characteristically formaldehyde is the principal aldehyde used. Mineral acids (sulfuric acid, phosphoric acid), p-toluenesulfonic acid, and ion exchange resins are the most frequent catalysts. Certain Lewis acids (BF3, ZnCl2, SnCl4) are, however, also effective. 

Oxidation with Palladium in the Homogeneous Phase. The most thoroughly studied reaction concerning the transformation of alkenes to carbonyl compounds is their oxidation catalyzed by palladium in homogeneous aqueous media.243 244 494-503 As a rule, ethylene is oxidized to acetaldehyde, and terminal alkenes are converted to methyl ketones.504 505... 

Although the oxidation of ethylene to acetaldehyde was known for a number of years,506 its utility depended on the catalytic regeneration of Pd(0) in situ with cop-per(II) chloride discovered by Smidt and coworkers.507 508 Air oxidation of Cu(I) to Cu(n) makes a complete catalytic cycle. This coupled three-step transformation is known as the Wacker process [Eqs. (9.97)-(9.99)]. The overall reaction [Eq. (9.100)] is the indirect oxidation with oxygen of alkenes to carbonyl compounds ... 

Resin-bound amines can be converted into imines [710,711] or enamines by reaction with carbonyl compounds (Entries 6 and 7, Table 3.39). Resin-bound enamines have also been prepared by Michael addition of resin-bound secondary amines to acceptor-substituted alkynes [712], by Hg(II)-catalyzed addition of resin-bound secondary amines to unactivated alkynes [713], by addition of C-nucleophiles to resin-bound imino ethers [714], and by chemical modification of other resin-bound enamines [712,713,715], Acceptor-substituted enamines ( push-pull alkenes) are not always susceptible to hydrolytic cleavage by TFA alone and might require aqueous acids to undergo hydrolysis [716]. 

NR = nonreactive toward hydrocarbons PO = oxidation of phosphines to phosphine oxides MF — peroxometallacyclic adduct formation with cyanoalkenes NSE — nonstereoselective epoxidation SE=stereoselective epoxidation AE = asymmetric epoxidation HA- hydroxylation of alkanes HB=hydroxylation of arenes OA = oxidation of alcohols to carbonyl compounds K = ketonization of Lermina 1 alkenes SO oxidation of S02 to coordinated S04 MO = metallaozonide formation with carbonyl compounds I = oxidation of isocyanides to isocyanates. 

Ylides of other elements have been used much less commonly than sulfur ylides in cyclopropanations. Rather, other ylides are better known for their uses in other types of reactions, the best example being the use of phosphonium ylides in the Wittig reaction with carbonyl compounds to give alkenes. Nonetheless, some cases of cyclopropanations have been reported with phosphonium ylides and the related arsenic derivatives. Examples are given in Table 9. 

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