Alkenes into unsaturated ketones

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Two different alkenes can be brought to reaction to give a [2 -I- 2] cycloaddition product. If one of the reactants is an o, /3-unsaturated ketone 11, this will be easier to bring to an excited state than an ordinary alkene or an enol ether e.g. 12. Consequently the excited carbonyl compound reacts with the ground state enol ether. By a competing reaction pathway, the Patemo-Buchi reaction of the 0, /3-unsaturated ketone may lead to formation of an oxetane, which however shall not be taken into account here ... 

Although hydrogenation of A-benzylideneaniline in the presence of 11 afforded the corresponding product (eq. 1 in Scheme 11), the a,(3-unsaturated ketone was converted into a mixture of unsaturated and saturated alcohols in the 42 56 ratio (eq. 2 in Scheme 11). Several substrates (nitrile derivatives, epoxides, esters, internal alkynes, and terminal alkenes), which are shown in Fig. 4, are not hydrogenated in this catalytic system. 

Nitroalkanes react with Jt-deficient alkenes, for example, p-nitro ketones are produced from a,P-unsaturated ketones [41], whereas allylic nitro compounds have been prepared via the Michael-type addition of nitroalkanes with electron-deficient alkynes (Table 6.19). The reaction in either dimethylsulphoxide [42] or dimethyl-formamide [43] is catalysed by potassium fluoride in the presence of benzyltriethyl-ammonium chloride the reaction with dimethyl acetylenedicarboxylate is only successful in dimethylsulphoxide [42], Primary nitroalkanes produce double Michael adducts [42,44], A-Protected a-aminoacetonitriles react with alkynes under catalysed solidiliquid conditions to produce the Michael adducts [45] which, upon treatment with aqueous copper(Il) sulphate, are converted into a,p-unsaturated ketones. 

In fluorosulfonic acid the anodic oxidation of cyclohexane in the presence of different acids (RCO2H) leads to a single product with a rearranged carbon skeleton, a 1-acyl-2-methyl-1-cyclopentene (1) in 50 to 60% yield (Eq. 2) [7, 8]. Also other alkanes have been converted at a smooth platinum anode into the corresponding a,-unsaturated ketones in 42 to 71% yield (Table 1) [8, 9]. Product formation is proposed to occur by oxidation of the hydrocarbon to a carbocation (Eq. 1 and Scheme 1) that rearranges and gets deprotonated to an alkene, which subsequently reacts with an acylium cation from the carboxylic acid to afford the a-unsaturated ketone (1) (Eq. 2) [8-10]. In the absence of acetic acid, for example, in fluorosulfonic acid/sodium... 

Polyamino acids are easy to prepare by nucleophUe-initiated polymerisation of amino acid JV-carboxyanhydrides. Polymers such as poly-(L)-leucine act as robust catalysts for the epoxi-dation of a wide range of electron-poor alkenes, such as y-substituted a,Ji-unsaturated ketones. The optically active epoxides so formed may be transformed into heterocyclic compounds, polyhydroxylated materials and biologically active compounds such as dUtiazem and taxol side chain. 

Insertion of alkenes into Os3H2(CO)10 gives compounds of the type Os3H(alkyl)(CO)10 which are usually reactive toward /(-elimination to regenerate alkene (see Section V) or reductive elimination of alkane to allow oxidative addition of the alkene (161,162). Sometimes, however, if the alkene is bi- or polyfunctional, stable insertion products are formed. For example, CH2=CHOMe inserts to give a mixture of diastereomers 71 and 72. Ether coordination reduces the rate of /(-elimination (243). Similar stabilization occurs on inserting a,/(-unsaturated esters (51), although a,/(-unsaturated ketones RCH—CHCOMe (R = H, Me, or Ph) insert, then eliminate the... 

In intermolecular cyclopropanations [100], it was found better to use a-bromoesters and amides as ylide precursors and a,/ -unsaturated ketones and esters as electron-deficient alkenes - rather than using a-haloketones as the ylide precursor. (For experimental details see Chapter 14.11.4). The reaction gives access to a range of 1,2-dicarbonyl-substituted cyclopropanes (see Fig. 10.5). The al-kene could have an aryl-, alkyl- or indole-substituted ketone, and a-substitution was also tolerated. Notably, Weinreb amides could be used as the ylide precursor and the product subsequently transformed into a diketocyclopropane. Both enan-... 

The reduction of a ketone to an alkene is feasible not only for unsaturated ketones (Figures 17.68 and 17.71) but for saturated ketones as well. To this end, the latter can be converted into enol phosphonoamidates or enol dialkylphosphonates via suitable lithium eno-lates. One substrate of each type is shown in Figure 17.73 (A and B). Lithium dissolved in EtNH2/iert-BuOH mixtures is a suitable reducing agent for both these compounds. Their Cvp2—O bond is cleaved by a sequence of three elementary steps with which you are famil-... 

Allylic diethylboranes.1 These boranes (2) can be prepared from 1-methyl-cycloalkenes and 2-alkenes by metallation with trimethylsilylmethylpotassium2 followed by reaction with 1. The products react with acetaldehyde to form homoallylic alcohols (3), which can be converted into a,(3- and p,y-unsaturated ketones. 

Activation of vinyl C-H bonds with RuH2(CO)(PPh3)3 catalyst has allowed the formal insertion of a,/l-unsaturated ketones or esters into the C-H bond of vinylsilanes and led to a regioselective C-C coupling at the -position [9] (Eq. 6). Activation of the sp2 C-H bond occurred with the aid of chelation of a coordinating functional group and provided vinylruthenium hydride 14. Insertion of olefin afforded the tetrasubstituted alkene 13. The ruthenium activation of a variety of inert C-H bonds has now been performed by Murai [10]. 

A similar selectivity was obtained by Nakazaki and coworkers for the cis-trans isomerization of doubly bridged alkenes in diethyl-( 4- )-tartrate. Upon irradiation at room temperature in this chiral solvent, m-bicyclic a,p-unsaturated ketone 13 was transformed into optically active (-)-trans-ketone 14 (Scheme... 

The overall mechanism of chromium(VI) allylic oxidation appears to craisist of removal of a hydrogen atom or hydride ion from the alkene, forming a resonance-stabilized allylic radical or carbocation, which is ultimately converted into die unsaturated ketone (Scheme 17). ... 

Terpenoids are subjected to aminomethylation in order to intrtxiuce a basic moiety into the molecule. The reactive site of the substrate is usually an alkene or alkyl ketone group however, unsaturated derivatives of type 490 arc obtained from terpenes suitably functionalized by the alkyne moiety. ... 

The alkene reduction reactions most frequently observed are of a,3-unsaturated aldehydes, ketones, acids and esters. Examples of stereospecific reductions of acyclic substrates are given in Scheme 50.148.157-159 (j, (, e formation of (123), the double bond of (122) is reduced prior to the aldehyde function. The conversion of (124) to (125) involves oxidation of the intermediate alcohol to the carboxylic acid by bubbling air into the fermentation medium. Stereospecific reductions of a, 3-unsaturated ketones may be similarly effected (Scheme 61). The reduction of the chloro ketone (126) gives (127) initially. This epimerizes under the reaction conditions, and each enantiomer is then reduced further to (128) and (129), with the predominance of the (128) stereoisomer increasing with the size of the R-group. Reduction of ( )-(130) leads to (131) and (132). ... 

The reduction of a carbon-carbon multiple bond by the use of a dissolving metal was first accomplished by Campbell and Eby in 1941. The reduction of disubstituted alkynes to c/ s-alkenes by catalytic hydrogenation, for example by the use of Raney nickel, provided an excellent method for the preparation of isomerically pure c -alkenes. At the time, however, there were no practical synthetic methods for the preparation of pure trani-alkenes. All of the previously existing procedures for the formation of an alkene resulted in the formation of mixtures of the cis- and trans-alkenes, which were extremely difficult to separate with the techniques existing at that time (basically fractional distillation) into the pure components. Campbell and Eby discovered that dialkylacetylenes could be reduced to pure frani-alkenes with sodium in liquid ammonia in good yields and in remarkable states of isomeric purity. Since that time several metal/solvent systems have been found useful for the reduction of C=C and C C bonds in alkenes and alkynes, including lithium/alkylamine, ° calcium/alkylamine, so-dium/HMPA in the absence or presence of a proton donor,activated zinc in the presence of a proton donor (an alcohol), and ytterbium in liquid ammonia. Although most of these reductions involve the reduction of an alkyne to an alkene, several very synthetically useful reactions involve the reduction of a,3-unsaturated ketones to saturated ketones. ... 

Excess hydridocobaltcarbonyl reduces a, -unsaturated ketones and aldehydes in moderate yield and good regioselectivity. The reaction involves complexation of the double bond to cobalt, followed by migratory insertion of hydride into the enone, forming an oxaallyl cobalt complex. Poor chemoselectivity is one of the major drawbacks of this reaction, as simple alkenes are rapidly hydroformylated to the corresponding aldehyde under the reaction conditions (25 °C, 1 atm of CO). 

Urea-hydrogen peroxide (UHP) has been found to epoxidize electron-deficient alkenes under various conditions <90SL533,93MI 103-03) for example, methyl methacrylate is epoxidized with UHP-Na2HP04 in the presence of (CF3C0)20 a,//-unsaturated ketones and nitroalkenes are cleanly transformed into the corresponding oxiranes with UHP-NaOH in methanol (Equation (37)). 

Into Alkenes, Allyl Alcohols, and a,P-Unsaturated Ketones (Decyanation Reaction)... 

Steroidal unsaturated ketones such as the 3-keto-4-enes were hydroxylated in the axial allylic C-6(3 position, possibly via the intervention of the enol. Several other fungal biotransformations of steroids have also been observed. These include epoxidation of alkenes, the conversion of the cyclopentanone of ring D into a 8-lactone and the degradation of the side-chain. 

Several examples are known of the enantioselective conversion of alkenes into epoxides with the use of polymer-supported oxidation catalysts. This can be traced to the pioneering work by Julia and Colonna in 1980. They demonstrated that highly enantioselective epoxidations of chalcones and related a, 3-unsaturated ketones can be achieved with the use of insoluble poly(a-amino acids) (116, Scheme 10.20) as catalysts [298-301]. The so-called Julia-Colonna epoxidation has been the object of several excellent reviews [302-306]. The terminal oxidant is H202 in aq. NaOH. With lipophilic amino acids as the components, such as (SJ-valine or (SJ-leucine, enantioselectivities as high as 96-97% ee were obtained. The enan-tioselectivity depends of several factors, including the side-chain of the amino acid, the nature of the end groups and the degree of polymerization. Thus, for instance,... 

Although it is not possible to prepare a,p-unsaturated dihydro-1,3-oxazines (84) by mere dehydration of the adducts (78), these alkenes can be prepared in good overall yields by Wittig-type reactions of carbonyl compounds with the phosphorus-substituted dihydro-1,3-oxazines (80-83 Scheme 30). Generally, better yields of (84) are obtained when aldehydes are employed as the reaction partners for the phosphoranes (80) and (81) and ketones are the reactants for the phosphonates (82) and (83). The a,p-unsaturated dihydrooxazines (84) are highly useful intermediates since they can be converted into a,p-unsaturated aldehydes (Scheme 30) as well as a,p-unsaturated ketones and carboxylic acids (Scheme 31).54... 

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