Carbonyl compounds reactivity enhancement

The reaction occurs quite instantaneously at —78 °C with n-BuLi86) or tert-BuLi 35,99 jn tHF, or with /m-BuLi in ether87. The availability of selenocyclo-propyllithiyms in the last solvent is particularly important since, for example, their nucleophilicity towards carbonyl compounds is enhanced under these conditions 871 (vide infra). However in this solvent sec- or tert-BuLi must be used 87) in place of -BuLi in order to obtain quantitative cleavage of the carbon-selenium bond. For example, l,l-bis(methylseleno)cyclopropane is recovered unchanged after addition of n-BuLi in ether at —78 °C or —40 DC. However, l,l-bis(phenylseleno)-cyclopropane is more reactive since, under these conditions, 35% of 1-lithio-l-phenylseleno cyclopropane is produced ". ... 

It is well known that in nitrogen-containing heterocyclic compounds the reactivity of alkyl groups is enhanced. In the thiazole series, alkyl groups in the 2-position are reactive towards carbonyl compounds and condensations may be realized. 

Diborane also has a useful pattern of selectivity. It reduces carboxylic acids to primary alcohols under mild conditions that leave esters unchanged.77 Nitro and cyano groups are relatively unreactive toward diborane. The rapid reaction between carboxylic acids and diborane is the result of formation of a triacyloxyborane intermediate by protonolysis of the B-H bonds. The resulting compound is essentially a mixed anhydride of the carboxylic acid and boric acid in which the carbonyl groups have enhanced reactivity toward borane or acetoxyborane. 

Silyl enol ethers and silyl ketene acetals also offer both enhanced reactivity and a favorable termination step. Electrophilic attack is followed by desilylation to give an a-substituted carbonyl compound. The carbocations can be generated from tertiary chlorides and a Lewis acid, such as TiCl4. This reaction provides a method for introducing tertiary alkyl groups a to a carbonyl, a transformation that cannot be achieved by base-catalyzed alkylation because of the strong tendency for tertiary halides to undergo elimination. 

Nucleophilic addition of metal alkyls to carbonyl compounds in the presence of a chiral catalyst has been one of the most extensively explored reactions in asymmetric synthesis. Various chiral amino alcohols as well as diamines with C2 symmetry have been developed as excellent chiral ligands in the enantiose-lective catalytic alkylation of aldehydes with organozincs. Although dialkylzinc compounds are inert to ordinary carbonyl substrates, certain additives can be used to enhance their reactivity. Particularly noteworthy is the finding by Oguni and Omi103 that a small amount of (S)-leucinol catalyzes the reaction of diethylzinc to form (R)-l-phenyl-1 -propanol in 49% ee. This is a case where the... 

Rate constants and Arrhenius parameters for the reaction of Et3Si radicals with various carbonyl compounds are available. Some data are collected in Table 5.2 [49]. The ease of addition of EtsSi radicals was found to decrease in the order 1,4-benzoquinone > cyclic diaryl ketones, benzaldehyde, benzil, perfluoro propionic anhydride > benzophenone alkyl aryl ketone, alkyl aldehyde > oxalate > benzoate, trifluoroacetate, anhydride > cyclic dialkyl ketone > acyclic dialkyl ketone > formate > acetate [49,50]. This order of reactivity was rationalized in terms of bond energy differences, stabilization of the radical formed, polar effects, and steric factors. Thus, a phenyl or acyl group adjacent to the carbonyl will stabilize the radical adduct whereas a perfluoroalkyl or acyloxy group next to the carbonyl moiety will enhance the contribution given by the canonical structure with a charge separation to the transition state (Equation 5.24). 

Trimethylsilyl triflate (McsSiOTf) acts as an even stronger Lewis acid than Sc(OTf)3 in the photoinduced electron-transfer reactions of AcrCO in dichloro-methane. In general, such enhancement of the redox reactivity of the Lewis acid complexes leads to the efficient C—C bond formation between organosilanes and aromatic carbonyl compounds via the Lewis-acid-catalyzed photoinduced electron transfer. Formation of the radical ion pair in photoinduced electron transfer from PhCHiSiMes to the (l-NA) -Mg(C104)2 complex (Scheme 11) and the AcrCO -Sc(OTf)3 complex (Scheme 12) was confirmed by the laser flash experiments [113]. 

A wide variety of compounds having the primary amino group condense with carbonyl compounds to give )C=N— compounds by the elimination of water. The latter reactions are usually acid catalyzed because protonation of the carbonyl group enhances its reactivity toward nucleophilic attack by the amino group on the carbonyl carbon atom (Eq. 1). 

A significant enhancement of reactivity of the carbonyl compound by complexation with Mg2+ has also been applied to a novel type of carbon-carbon bond formation via photoinduced electron transfer from unsymmet-rically substituted acetal (5) with benzophenone (6) (Scheme 26) [211]. This photochemical reaction takes place in the absence of Mg2+ in MeCN. However, the yield of the desired carbon-carbon coupling product 7 is only 15% together with radical dimers 8 (28%) and 9 (2%). Addition of Mg(C104)2 to this system results in a much higher yield of 7 (e.g., 78%) at the expense of radical dimer formation [211]. Thus, the initial photoinduced electron transfer may be catalyzed by Mg2+ to produce a radical ion pair (6 "-Mg2+5 +), where 6 is stabilized by the complexation with Mg2+, as shown in Scheme 26 [211]. The efficient C-C bond formation occurs in the radical ion pair, followed by cyclization before and after desilylation to produce various types of products (Scheme 26). 

In all cases, superelectorophilic dicationic intermediates3 5 were suggested to be involved in the activation of carbonyl compounds based on the observation that protonated /V-heterocycles significantly enhance the reactivity of adjacent carbo-cationic centers. For example, cyclohexanone and acetophenone are unreactive toward benzene in triflic acid, whereas 4-piperidones252 and acetylpyridines254 react readily. Likewise, 3-pyridinecarboxaldehyde is able to alkylate deactivated... 

Without protonation of the carbonyl group, weak nucleophiles (TV,/V-dime-thylaniline and phenol) would only react slowly or not at all with the carbonyl groups. Similarly, complexation with Lewis acids can enhance the electrophilic reactivities of carbonyl compounds. This occurs by decreasing participation (using Winstein s concept) of the neighboring oxygen... 

The polar properties of the alpha-C-H bonds and their reactivity towards hydrogen atom abstraction in acetals are enhanced by the presence of two ether groups. These hydrogens are susceptible to abstraction by excited carbonyl compounds (77). Cleavage of C—0 bonds in acetals occurs readily when an acetal radical is formed (38) even at room temperature. It has been shown that irradiation of cyclic acetals of aldehydes at room temperature in the presence of acetone leads to the appropriate carboxylic esters (22),... 

Aldol reaction. Quantitative yields of 1,2-adducts of alkyllithiums to ketones can be obtained at -65° in the presence of Cel,. Cerium enolates, formed by reaction of CeCl, with lithium enolates, also show enhanced reactivity in reactions with carbonyl compounds, particularly ketones. Yields of aldols are increased, but the stereoselectivity remains moderate. ... 

Assessment of the role of the cation in MPV reduction is difficult, Conversion of alcohol to alkoxide certainly enhances the reactivity towards hydride donation, and aluminum ions aid via chelation in arranging alkoxide and carbonyl compound properly for reaction. However, alkoxides bearing cations other than aluminum may also exhibit good hydride-donating tendencies. Lithium isopropoxide reduces steroidal ketones efficiently and magnesium alkoxides derived from chiral alcohols have been used extensively in chiral syntheses. Isobomyloxy magnesium bromide (52) has been used widely for this purpose (equation 27). ... 

The enhanced reactivity of oxiranes due to geometric strain is manifested in their acid- and base-catalyzed reactions, in their rearrangements in the presence of metals and metal compounds, and in their thermal and photocatalytic transformations. These reactions permit the development of new and varied methods of synthesis and the preparation of derivatives that in many cases are difficult to obtain by other routes. The main products of the isomerization reaction are unsaturated alcohols and carbonyl compounds. Great progress has been made in this area of organic chemistry during the past 20 years (The reader is referred to some relevant... 

The above-mentioned requirements of low basicity and fast alkyl transfer are combined in alkylzirco-nium(IV) species, like tetramethylzirconium which readily methylates enolizable and highly hindered carbonyl compounds such as (62 equation 26). The presence of several alkyl groups on the metal atom imparts enhanced reactivity to the species due to the absence of ir-bond-forming electron-donor heteroatoms. In fact, tetramethylzirconium can be regarded as a supermethylating agent, evidenced by the conversion of (65) into (66 equation 27). ... 

Because of its enhanced reactivity, diethoxyvinylidenetriphenylphosphorane adds a variety of CH acids, even those which do not react with 0x0-, thioxo- and imino-vinylidenetriphenylphosphorane. Irreversible loss of ethanol from the initially formed Michael adduct gives phosphoranes which are vinylogs of 3-keto ylides if the starting material is an acidic carbonyl compound (equation lOS). CH-acidic carbonyl compounds also may add to diethoxyvinylidenetriphenylphosphorane via the enolate oxygen, thus leading to orthoester phosphoranes which can undergo intramolecular Wittig reaction. ... 

Domingo, L. R., Andres, J. Enhancing Reactivity of Carbonyl Compounds via Hydrogen-Bond Formation. A DFT Study of the Hetero-Diels-Alder Reaction between Butadiene Derivative and Acetone in Chloroform. J. Org. Chem. 2003, 68, 8662-8668. 

The intermediates formed in AOPs sometimes are more toxic than the parent compounds and are required to be decomposed completely using either combination of AOPs or combination of AOP and some other treatment methods such as adsorption and biodegradation. Carbonyl compounds, particularly aldehydes, are quite toxic, and some of the secondary compounds formed from aldehydes, especially peroxyacylnitrates are more dangerous than the parent compounds. Organic peroxy radical (ROj) reactions are of significance because they represent an important class of intermediates formed in the oxidation process of hydrocarbons (15). Intermediates such as ethers and alcohols have enhanced reactivity toward hydroxyl radical. The rate constant of oxidation of these compounds is of similar order of magnitude as of the alkanes. 

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