Alkenes into carbonyl compounds

The perruthenate oxidation of alcohols has been incorporated into a one-pot conversion of alkenes into carbonyl compounds via their initial hydroboration [44], Overall yields can be as high as 98%. Where the initial alkene also contains carbonyl groups these are reduced in the first step and are reoxidized by the perruthenate. 

The deoxygenation of epoxides is not of great preparative value since it involves some loss of stereochemical integrity and the alkenes produced are more readily approached in other ways. Reductive cleavage of ozonides, for example, using triphenylphosphine, commonly forms part of the ozonolysis procedure for conversion of alkenes into carbonyl compounds. If a carbonyl compound is treated with an appropriate P(III) reagent then the reverse process may occur—reductive coupling to form a new C=C double bond. This has found a particularly important... 

Since nucleophilic addition to a metal-coordinated alkene generates a cr-metal species bonded to an -hybridized carbon, facile 3-H elimination may then ensue. An important example of pertinence to this mechanism is the Wacker reaction, in which alkenes are converted into carbonyl compounds by the oxidative addition of water (Equation (108)), typically in the presence of a Pd(n) catalyst and a stoichiometric reoxidant.399 When an alcohol is employed as the nucleophile instead, the reaction produces a vinyl or allylic ether as the product, thus accomplishing an etherification process. 

Substrates suitable for oxidative conversion into carbonyl compounds are alkenes, primary or secondary alcohols, and benzyl halides. Polystyrene-bound alkenes have been converted into aldehydes (with the loss of one carbon atom) by ozonolysis followed by reductive cleavage of the intermediate ozonide (Entry 1, Table 12.3). 

Sodium periodate (sodium metaperiodate), NaI04 (mp 300 °C dec), which is commercially available, is applied mainly in aqueous or aqueous-alcoholic solutions. Like the free periodic acid, sodium periodate cleaves vicinal diols to carbonyl compounds [762], This reaction is especially useful in connection with potassium permanganate [763, 764] or osmium tetroxide [765], Such mixed oxidants oxidize alkenes to carbonyl compounds or carboxylic acids, evidently by way of vicinal diols as intermediates. Sulfides are transformed by sodium periodate into sulfoxides [322, 323, 766, 767, 768, 769, 770, 771, 772], and selenides are converted into selenoxides [773]. Sodium periodate is also a reoxidant of lower valency ruthenium in oxidations with ruthenium tetroxide [567, 774],... 

Primary alcohols are oxidized to aldehydes or acids, and secondary alcohols are oxidized to ketones. Tertiary alcohols resist oxidation, unless they are dehydrated in acidic media to alkenes, which are subsequently oxidized. The conversion of alcohols into carbonyl compounds can be achieved by catalytic dehydrogenation or by chemical oxidation. Catalytic dehydrogenation is especially of advantage with primary alcohols, because it prevents overoxidation to carboxylic acids. Examples are tabulated in equations 223-227 and 265-268. 

The ethynyl moiety is a versatile group for numerous chemical transformations. It is readily introduced onto a variety of organic substrates via ethynylation or coupling reactions (see Chapter 7) and provides a reaction site for manifold further modifications. The following discussion will be centered on the conversion of alkynes into stereodefined alkenes and into carbonyl compounds. 

Otymercuration (Section 10.3) The mercury-catalyzed conversion of alkenes into alcohols. Addition is in the Markovnikov sense, and there are no rearrangements. A three-membered ring containing mercury is an intermediate in the reaction. Alkynes also undergo oxymercuration to give enols that are rapidly converted into carbonyl compounds under the reaction conditions. 

The aim of this Chapter is to examine the application of well-defined N-hetero-cyclic carbene (NHC) complexes as well as the systems prepared in situ which involve free NHCs or the precursor salt for the reduction of imsaturated organic molecules such as alkynes, alkenes and carbonyl compounds. The most active complexes for such reductions contain electron-rich, late transition metals in low oxidation states. Herein, reductions useful for organic synthesis will be classified into four types aeeording to reductants used (i) hydrogenations, (ii) transfer hydrogenation, (iii) hydrosilylation and (iv) hydroboration. For examples of reduction reactions with systems containing non-classical NHC ligands, the reader is referred to Chapter 5. 

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 ... 

Alkenes are reduced by addition of H2 in the presence of a catalyst such as platinum or palladium to yield alkanes, a process called catalytic hydrogenation. Alkenes are also oxidized by reaction with a peroxyacid to give epoxides, which can be converted into lTans-l,2-diols by acid-catalyzed epoxide hydrolysis. The corresponding cis-l,2-diols can be made directly from alkenes by hydroxylation with 0s04. Alkenes can also be cleaved to produce carbonyl compounds by reaction with ozone, followed by reduction with zinc metal. 

Ihmels H, Otto D (2005) Intercalation of Organic Dye Molecules into Double-Stranded DNA - General Principles and Recent Developments. 258 161-204 Iida H, Krische MJ (2007) Catalytic Reductive Coupling of Alkenes and Alkynes to Carbonyl Compounds and Imines Mediated by Hydrogen. 279 77-104 Imai H (2007) Self-Organized Formation of Hierarchical Structures. 270 43-72 Indelli MT, see Chiorboli C (2005) 257 63-102 Inoue Y, see Borovkov VV (2006) 265 89-146 Ishii A, Nakayama J (2005) Carbodithioic Acid Esters. 251 181-225 Ishii A, Nakayama J (2005) Carboselenothioic and Carbodiselenoic Acid Derivatives and Related Compounds. 251 227-246... 

Insertion of carbon monoxide into Csp2—Zr bonds occurs readily at ambient temperatures or below to produce a,(5-unsaturated, reactive acyl zirconocene derivatives [27—29]. Early work by Schwartz demonstrated the potential of such intermediates in synthesis [5d], as they are highly susceptible to further conversions to a variety of carbonyl compounds depending upon manipulation. More recently, Huang has shown that HC1 converts 16 to an enal, that addition of a diaryl diselenide leads to selenoesters, and that exposure to a sulfenyl chloride gives thioesters (Scheme 4.11) [27,28]. All are obtained with (F)-stereochemistry, indicative of CO insertion with the expected retention of alkene geometry. 

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. 

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... 

Generation of the carbon based radical in these processes involves the prior formation of a complex between manganese(lll) and the enol of the carbonyl reactant. Intramolecular electron transfer occurs within this complex. Addition to the olefin then takes place within the co-ordination sphere of manganese. When manganese is present in catalytic amount, the relative values of the equlibrium constants between manganese and both the carbonyl compound and the alkene arc important. If the olefm is more strongly complexed then no radical can form and reaction ceases. Reactions are usually carried out at constant current and the current used must correspond to less than the maximum possible rate for the overall chemical steps involved. Excess current caused the anode potential to rise into a region where Kolbe reaction of acetate can occur and this leads to side reactions [28]. 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

One of the most important features of the ozonolysis reaction of alkenes is one in which ozone adds to the C=C bond to form a primary ozonide (1,2,3-trioxolane). The Criegee mechanism suggests that this unstable intermediate decomposes into a carbonyl compound and a carbonyl oxide that recombine to form a final isomeric ozonide (1,2,4-trioxolane). Direct spectroscopic evidence for a substituted carbonyl oxide has only recently been reported by Sander and coworkers for the NMR characterization of dimesityl carbonyl oxide. Kraka and coworkers have theoretically modeled dimesityl carbonyl oxide and confirmed the structural aspects reported by Sander and coworkers on the basis of NMR data. 

The role of titanium salt is to activate the carbonyl compounds as Lewis acid. As described above, bis(iodozincio)methane (3) is nucleophilic enough to attack the carbonyl group of aldehydes or ce-alkoxyketones. In the reaction with simple ketones or esters, however, the addition of titanium salt is necessary to facilitate the nucleophilic attack. Instead of this Lewis acid activator, simple heating may induce the nucleophilic attack. Treatment of 2-dodecanone with 3 without titanium salt at higher temperature, however, does not improve the yield of alkene (Scheme 13). The reason for the low reactivity of 3 at higher temperature comes from the structural change of 3 into the polymeric methylene zinc 4 through the Schlenk equilibrium shown in equation 740. 

By far the most widespread type of photocycloaddition in synthetic applications employs the afkene unit of an c. p u nsaturated carbonyl compound as one of the addends. Simpleexamplesof such reactions are the dimerization of cyclopent-2-ennne (2.71), and the photo-addiiion of 2-methylptopene to cyclohex-2-enone (2.72). The function of the carbonyl group is to bring the absorption of the alkene into... 

Dipolar cycloaddition reactions between nitrile oxides and alkenes produce 2-isoxazolines. Through reductive cleavage of the N—O bond of the 2-isoxazolines, the resulting heterocycles can be readily transformed into a variety of important synthetic intermediates such as p-hydroxy ketones (aldols), p-hydroxy esters, cc,p-unsaturated carbonyl compounds, y-amino alcohols, imino ketones and so forth (7-12). 

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