Carbonyl compounds, addition reactions acetal formation

Durandetti et al. have described iron-catalyzed electrochemical allylation of carbonyl compounds with allylic acetates (Equation (27)).333 In the case of aldehydes, slow addition of the corresponding aldehyde is required in order to avoid pinacol formation. With crotyl acetate (R3 = Me), the reaction proved to be highly regioselective, providing almost exclusively branched homoallylic alcohols 150. 

The equilibrium constants for addition of alcohols to carbonyl compounds to give hemiacetals or hemiketals show the same response to structural features as the hydration reaction. Equilibrium constants for addition of metiianoHb acetaldehyde in both water and chloroform solution are near 0.8 A/ . The comparable value for addition of water is about 0.02 The overall equilibrium constant for formation of the dimethyl acetal of... 

Purely aromatic ketones generally do not give satisfactory results pinacols and resinous products often predominate. The reduction of ketonic compounds of high molecular weight and very slight solubility is facilitated by the addition of a solvent, such as ethanol, acetic acid or dioxan, which is miscible with aqueous hydrochloric acid. With some carbonyl compounds, notably keto acids, poor yields are obtained even in the presence of ethanol, etc., and the difficulty has been ascribed to the formation of insoluble polymolecular reduction products, which coat the surface of the zinc. The adffition of a hydrocarbon solvent, such as toluene, is beneficial because it keeps most of the material out of contact with the zinc and the reduction occurs in the aqueous layer at such high dilution that polymolecular reactions are largdy inhibited (see Section IV,143). 

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). 

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]. 

URECH CYANOHYDRIN METHOD. Cyanohydrin formation by addition of alkali cyanide to the carbonyl group in the presence of acetic acid (Urech) or by reaction of the carbonyl compound with anhydrous hydrogen cyanide in the presence of basic catalyst (Ultee). 

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). 

The most important reaction examples for the formation of IVW-acetals involve formaldehyde because it tends more than most other carbonyl compounds to undergo additions (Section 9.1.1). With ammonia formaldehyde gives hexamethylenetetramine (Figure 9.24). This compound contains six lYW-acetal subunits. 

The survey in Figure 9.23 shows that N nucleophiles can react with carbonyl compounds in the following ways (1) An addition to the C=0 double bond followed by an SN1 reaction leads to the formation of AW-acetals (details Section 9.2.4). (2) An addition to the C=0 double bond is followed by an El reaction by which, amongst others, enamines are formed (details Section 9.3). (3) Imines are produced. We still need to discuss whether the reaction of O nucleophiles with carbonyl compounds also gives us two options—parallel to the two possibilities (1) and (2) mentioned above. According to Figure 9.12 alcohols and carbonyl compounds always afford 0,0-acetals—through an addition and an SN1 reaction (details Section 9.2.2). 

The alternative to this 0,0-acetal formation is the sequence of addition and El reaction. As a matter of fact, this is familiar from the transformation of alcohols with carbonyl compounds, but only occurs in some (very rare) cases. This is illustrated by Figure 9.31 using acid-catalyzed transformations of ethanol with two /3-diketones as an example. Here, enol ethers, namely 3-ethoxy-2-cyclopentene-l-one and 3-ethoxy-2-cyclohexene-l-one, respectively, are... 

Although there exist numerous ground state reactions, photochemically induci asymmetric radical additions can be very efficient and even highly stereoselectr [125]. Furthermore, no particular functionalization of the starting material is n< essary prior to the formation of a C-C bond. In this context, the photosensiti addition of alcohols, cyclic acetals, and tertiary amines to electron-deficient kenes has been particularly studied. This will be illustrated by a few exampli First attempts to induce chirality in the photoinduced addition of ket radicals (e.g., U) involved a, 3-usaturated carbonyl compounds such as 208 rived from carbohydrates (Scheme 56) [126]. With benzophenone as sensitizi these radicals could be added stereoselectively, and similar reactions were carri out with dioxolane and a, 3-usaturated nitropyranones [127]. 

Addition of anionic nucleophiles to alkenes and to heteronuclear double bond systems (C=0, C=S) also lies within the scope of this Section. Chloride and cyanide ions are effieient initiators of the polymerization and copolymerization of acrylonitrile in dipolar non-HBD solvents, as reported by Parker [6], Even some 1,3-dipolar cycloaddition reactions leading to heterocyclic compounds are often better carried out in dipolar non-HBD solvents in order to increase rates and yields [311], The rate of alkaline hydrolysis of ethyl and 4-nitrophenyl acetate in dimethyl sulfoxide/water mixtures increases with increasing dimethyl sulfoxide concentration due to the increased activity of the hydroxide ion. This is presumably caused by its reduced solvation in the dipolar non-HBD solvent [312, 313]. Dimethyl sulfoxide greatly accelerates the formation of oximes from carbonyl compounds and hydroxylamine, as shown for substituted 9-oxofluorenes [314]. Nucleophilic attack on carbon disulfide by cyanide ion is possible only in A,A-dimethylformamide [315]. The fluoride ion, dissolved as tetraalkylammo-nium fluoride in dipolar difluoromethane, even reacts with carbon dioxide to yield the fluorocarbonate ion, F-C02 [840]. 

Coverage in this chapter is restricted to the use of alkenes or alkynes as enophiles (equation 1 X = Y = C) and to the use of ene components in which a hydrogen is transferred. Coverage in Sections 1.2 and 1.3 is restricted to ene components in which all three heavy atoms are carbon (equation 1 Z = C). Thermal intramolecular ene reactions of enols (equation 1 Z = O) with unactivated alkenes are presented in Section 1.4. Metallo-ene reactions are covered in the following chapter. Use of carbonyl compounds as enophiles, which can be considered as a subset of the Prins reaction, is covered in depth in Volume 2, Chtqiter 2.1. Addition of enophiles to vinylsilanes and allylsilanes is covered in Volume 2, Chapter 2.2, while addition of enophiles to enol ethers is covered in Volume 2, Chapters 2.3-2.S. Addition of imines and iminium compounds to alkenes is presented in Volume 2, Part 4. Use of alkenes, aldehydes and acetals as initiators for polyene cyclizations is covered in Volume 3, Chapter 1.9. Coverage of singlet oxygen, azo, nitroso, S=N, S=0, Se=N or Se=0 enophiles are excluded since these reactions do not result in the formation of a carbon-carbon bond. 

The Michael addition (1,4-conjugate addition) of an enolate to an ot, -unsaturated carbonyl system is another prevalent reaction for carbon-carbon bond formation (75, 76). However, its use in organic syntheses is occasionally restricted owing to a concurrent 1,2-addition reaction and polymerization of a, -unsaturated carbonyl compounds. A new methodology to overcome these problems has been devised by the use of lithium enolates (77-79). Another approach is to use silyl enol ethers and silyl ketene acetals as enolates. 

---