Carbonyl compounds Subject

Chiral salen chromium and cobalt complexes have been shown by Jacobsen et al. to catalyze an enantioselective cycloaddition reaction of carbonyl compounds with dienes [22]. The cycloaddition reaction of different aldehydes 1 containing aromatic, aliphatic, and conjugated substituents with Danishefsky s diene 2a catalyzed by the chiral salen-chromium(III) complexes 14a,b proceeds in up to 98% yield and with moderate to high ee (Scheme 4.14). It was found that the presence of oven-dried powdered 4 A molecular sieves led to increased yield and enantioselectivity. The lowest ee (62% ee, catalyst 14b) was obtained for hexanal and the highest (93% ee, catalyst 14a) was obtained for cyclohexyl aldehyde. The mechanism of the cycloaddition reaction was investigated in terms of a traditional cycloaddition, or formation of the cycloaddition product via a Mukaiyama aldol-reaction path. In the presence of the chiral salen-chromium(III) catalyst system NMR spectroscopy of the crude reaction mixture of the reaction of benzaldehyde with Danishefsky s diene revealed the exclusive presence of the cycloaddition-pathway product. The Mukaiyama aldol condensation product was prepared independently and subjected to the conditions of the chiral salen-chromium(III)-catalyzed reactions. No detectable cycloaddition product could be observed. These results point towards a [2-i-4]-cydoaddition mechanism. 

This area of reactivity has been the subject of excellent reviews (J5). Silyl enol ethers are not sufficiently nucleophilic to react spontaneously with carbonyl compounds they do so under the influence of either Lewis acids or fluoride ion, as detailed above. Few clear trends have emerged from the somewhat limited number of definitive studies reported so far, with ambiguities in diastereoisomeric assignments occasionally complicating the issue even further. 

Carbonyl reactions are extremely important in chemistry and biochemistry, yet they are often given short shrift in textbooks on physical organic chemistry, partly because the subject was historically developed by the study of nucleophilic substitution at saturated carbon, and partly because carbonyl reactions are often more difhcult to study. They are generally reversible under usual conditions and involve complicated multistep mechanisms and general acid/base catalysis. In thinking about carbonyl reactions, 1 find it helpful to consider the carbonyl group as a (very) stabilized carbenium ion, with an O substituent. Then one can immediately draw on everything one has learned about carbenium ion reactivity and see that the reactivity order for carbonyl compounds ... 

Rates of addition to carbonyls (or expulsion to regenerate a carbonyl) can be estimated by appropriate forms of Marcus Theory. " These reactions are often subject to general acid/base catalysis, so that it is commonly necessary to use Multidimensional Marcus Theory (MMT) - to allow for the variable importance of different proton transfer modes. This approach treats a concerted reaction as the result of several orthogonal processes, each of which has its own reaction coordinate and its own intrinsic barrier independent of the other coordinates. If an intrinsic barrier for the simple addition process is available then this is a satisfactory procedure. Intrinsic barriers are generally insensitive to the reactivity of the species, although for very reactive carbonyl compounds one finds that the intrinsic barrier becomes variable. ... 

Et2Zn also participates in the reductive coupling as a formal hydride source. Results for the Ni-catalyzed, Et2Zn-promoted homoallylation of carbonyl compounds with isoprene are summarized in Table 7 [30]. Et2Zn is so reactive that for the reaction with reactive aromatic aldehydes it causes direct ethylation of aldehydes, and the yields of homoallylation are diminished (runs 1 and 2). Unsaturated aldehydes seem to be subject to the Michael addition of Et2Zn. Accordingly, for the reaction with cinnamaldehyde, none of the expected homoallylation product is produced instead, the 1,4-addition product of Et2Zn, 3-phenylpentanal is produced exclusively (run 3). 

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... 

To illustrate the overall magnitude of the mechanistic problem, let us consider the varied reactivity of a prototypical carbonyl compound such as acetone, which is subject to many diverse reactions such as addition, substitution, cycloaddition, oxidation, reduction, etc., as illustrated in Chart 2. 

Dimerizations of oc,/ -unsaturated carbonyl compounds are perhaps the most interesting reactions, and certainly are the subjects of the most wide-spread investigations. Many are photosensitized, including that of coumarin, Eq. 50. 123> Other reactions of simple enones also involve... 

The epoxidation of electron-deficient alkenes, particularly a,P-unsaturated carbonyl compounds, continues to generate much activity in the literature, and this has been the subject of a recent concise review <00CC1215>. Additional current contributions in this area include a novel epoxidation of enones via direct oxygen atom transfer from hypervalent oxido-).3-iodanes (38), a process which proceeds in fair to good yields and with complete retention of... 

This article shows a variety of patterns of electrochemical oxidation of oxygen-containing compounds (alcohols, carbonyl compounds, and carboxylic acids), aiming to be helpful for both electroorganic and organic chemists to cover this field from a synthetic viewpoint. Since there have been excellent books [1-5] published on the subject, this article quotes only some typical and important papers from before 1990. 

Another advantage of this method is that no catalyst is needed for the addition reaction this means that the base-catalyzed polymerization of the electrophilic olefin (i.e., a,j8-unsaturated ketones, esters, etc.) is not normally a factor to contend with, as it is in the usual base-catalyzed reactions of the Michael typCi It also means that the carbonyl compound is not subject to aldol condensation which often is the predominant reaction in base-catalyzed reactions. An unsaturated aldehyde can be used only in a Michael addition reaction when the enamine method is employed. 

Whilst reactions of a, -unsaturated carbonyl compounds with 2 have been the subject of a number of studies, the corresponding reactions of their enolic tautomers have received little attention. Reaction of the /S-hydroxy-a, /i-unsaturated ketones... 

A range of nitrogen, phosphorus, chalcogen (O, S, Se) and halogen electrophiles react with enamines, resulting in a net a-functionalization of the carbonyl compound. In the past five years, all of these reaction variants have been subjected to asymmetric enamine catalysis, with excellent results. 

The Bingel reaction is not restricted to C-H-acidic carbonyl compounds such as malonates. Various other substrates have also been used. Some C-H-acidic compounds, which were successfully subjected to the Bingel reaction, are shown in Table 3.1. 

An alternative method to TBARS for determination of MDA is formation of the DNP derivative and quantitation by RP-HPLC with DA-UVD, recording in the 195 to 500 nm range. Other carbonyl compounds present in the sample also form the corresponding DNP compounds and are also determined. The method was applied to MDA determination in plasma of rats, after they were subjected to oxidative stress by intraparental injection of a dose of bacterial lipopolysaccharide" . 

Meerwein-Pondorf-Verley reduction, discovered in the 1920s, is the transfer hydrogenation of carbonyl compounds by alcohols, catalyzed by basic metal compounds (e.g., alkoxides) [56-58]. The same reaction viewed as oxidation of alcohols [59] is called Oppenauer oxidation. Suitable catalysts include homogeneous as well as heterogeneous systems, containing a wide variety of metals like Li, Mg, Ca, Al, Ti, 2r and lanthanides. The subject has been reviewed recently [22]. In this review we will concentrate on homogeneous catalysis by aluminium. Most aluminium alkoxides will catalyze MPV reduction. 

Recall that the LUMO shows which regions of a molecule are most electron deficient, and hence most subject to nucleophilic attack. One such region is over the carbonyl carbon, consistent with the observation that carbonyl compounds undergo nucleophilic addition at the carbonyl carbon. Another region is over the P carbon, again consistent with the known chemistry of a,P-unsaturated carbonyl compounds, in this case conjugate or Michael addition. 

In general, carbonyl compounds that are reactive in the photocycloaddition reaction are also reduced upon irradiation in isopropyl alcohol.17 Subject to the limitation of triplet-triplet transfer to the olefin mentioned previously, the converse is also true. That is, carbonyl compounds that are photoreduced in isopropyl alcohol can form oxetanes unless their triplet energies are high enough for the olefins to act as quenchers. Thus, the two reactions are characteristic of the same type of excited state. (This is not an exclusive generalization.) The quenching experiments mentioned on pp. 308-311 provide evidence that the reactive state can be the triplet and, in some cases, only the triplet. Evidence for this state being n,ir comes from the fact that carbonyl compounds which are reactive usually emit from the n,n triplet, while those which are unreactive emit from some other excited state. 

New synthetic routes (Scheme 9) to photosensitive linear and angular furocoumarins, furoquinolones, furoquino-lines, and their analogs were the subject of a review <2004MOL50>. It focuses on the Fries rearrangement of acyloxyheteroarenes, like 70 — 71, the condensation of acylhydroxyheteroarenes with a-carbonyl compounds, like 72 73, and the transformations of dihydrofuroheteroarenes, like 74 75. 

Reduction of aldehydes and ketones. Earlier work on amine borane reagents was conducted mainly with tertiary amines and led to the conclusion that these borane complexes reduced carbonyl compounds very slowly, at least under neutral conditions, and that the yield of alcohols is low. Actually complexes of borane with primary amines, NHj or (CH3)3CNH2, reduce carbonyl compounds rapidly and with utilization of the three hydride equivalents. BH3 NH3 is less subject to steric effects than traditional complex hydrides. A particular advantage is that NH3 BH3 and (CH3)3CNH2 BH3 reduce aldehyde groups much more rapidly than keto groups, but cyclohexanone can be reduced selectively in the presence of aliphatic and aromatic acyclic ketones. 

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