Addition of alcohols to carbonyl compounds

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... 

Addition of alcohol to carbonyl compounds preparation of acetal and ketal... 

In Chaptare we discussed the role of base and ecid catalysts in the direct addition of alcohols to carbonyl compounds to form hemiacetals. The reasoning—that base makes nucleophiles more nucleophilic and acid makes carbonyl groups more electrophilic—is the same here. 

The cyclizations of 85 to 86 and of 87 to 88 represent the simple cases in which the internal nucleophile is the OH group of an alcohol [64,65]. An in situ generated hydroxy group, as in the addition of alcohols to carbonyl compounds, can also participate in phenylseleno-etherification reactions. This is examplified by the conversion of 89 into 90 in the presence of benzyl alcohol [66]. Another type of OH, which gives rise to these reactions is the enolic OH of /1-dicarbonyl compounds. Thus, Ley reported that compounds like 91 and 93 can be transformed into the cyclic derivatives 92 and 94 by treatment with N-PSP 11 in the presence of zinc iodide [67]. The cyclization of 95 to 96 represents a simple example of the selenolactonization process [68, 69]. It is interesting to note that the various cyclization reactions indicated in Scheme 14, which require different electrophilic selenenylating agents, can all be effected with phenyselenyl sulfate [70]. 

The equilibrium constants for addition of alcohols to carbonyl compounds to give hemiacetals or hemiketals show the same response to structural features as do those for hydration reactions. The magnitude of the equilibrium constants is slightly smaller than for hydration. For example, whereas K for addition of water to acetaldehyde is 1.06, K s for addition of methanol and ethanol are 0.75 and 0.50 M respectively. The overall equilibrium constants for formation of the acetals are 0.03 and 0.0125 M , respectively. Because the position of the equilibrium does not favor product, the formation of acetals and ketals must be carried out in such a way as to compensate for the unfavorable equilibrium. One approach is to use a dehydrating reagent or azeotropic distillation so that the water that is formed is irreversibly removed, driving the reaction to completion ... 

Alcohols can be synthesized by the addition of carbanions to carbonyl compounds (W.C. Still, 1976) or epoxides. Both types of reactions often produce chiral centres, and stereoselectivity is an important aspect of these reactions. 

The basc-eatalyzcd addition of nilroalkancs to carbonyl compounds is a reversible reaction and proceeds under thermodynamic control. Thus low (R, R )/(R, S ) selectivities arc observed in the classical Henry reaction which leads to the silylated x-nitro alcohols 2. 

In the remainder of Chapter 12, the oxidation of alkenes, alkynes, and alcohols— three functional groups already introduced in this text—is presented (Figure 12.8). Addition reactions to alkenes and alkynes that increase the number of C—O bonds are described in Sections 12.8-12.11. Oxidation of alcohols to carbonyl compounds appears in Sections 12.12-12.14. 

Dimethyl sulfoxide (DMSO), (CH3)2SO, is a versatile reagent for the oxidation of alcohols to carbonyl compounds under gentle conditions. In addition to the previously mentioned dehydrogenations, it is capable of other oxidations acetylenes to a-diketones [997], alkyl halides to aldehydes 998, 999], tosyl esters to aldehydes [1000], methylene groups adjacent to carbonyl groups to carbonyls [1001, 1002], a-halocarbonyl compounds to u-dicarbonyl compounds [1003,1004,1005], aldehydes to acids [1006], and phosphine sulfides and selenides to phosphine oxides [1007]. 

Alcohols can be obtained from many other classes of compounds such as alkyl halides, amines, al-kenes, epoxides and carbonyl compounds. The addition of nucleophiles to carbonyl compounds is a versatile and convenient methc for the the preparation of alcohols. Regioselective oxirane ring opening of epoxides by nucleophiles is another important route for the synthesis of alcohols. However, stereospe-cific oxirane ring formation is prerequisite to the use of epoxides in organic synthesis. The chemistry of epoxides has been extensively studied in this decade and the development of the diastereoselective oxidations of alkenic alcohols makes epoxy alcohols with definite configurations readily available. Recently developed asymmetric epoxidation of prochiral allylic alcohols allows the enantioselective synthesis of 2,3-epoxy alcohols. 

Addition products of alcohols to carbonyl compounds (hemiacetals) can be isolated only in a few cases. They are stable only if the original carbonyl group is markedly electron-deficient, as is the case with chloral from which a series of semiacetals (1) has been isolated 901 Similarly the semiacetals (2) and (3) of ethyl glyoxalate902 and cyclopropenone,903 respectively, have been isolated. 

Addition of silylacetylenes to carbonyl compounds This salt catalyzes the addition of l-phenyl-2-trimethylsilylacetylene (1) to aldehydes or ketones at room temperature to form adducts which can be isolated in the silylated form (2) or as alcohols (3). The reaction of (a) with ,)S-unsaturated carbonyl compounds is generally not useful. See Ethyl trimethylsilylacelate-Tetra-ii-butylannnoniani fluoride, this volume. 

Catalytic amounts of TBAF promote the addition of organosilanes to carbonyl compounds. Examples of this approach include allylation of aldehydes to give allylic alcohols (eq 40) and the preparation of a-fluoroallylic alcohols from benzaldehyde (eq41). ... 

This addition of organometaUic to carbonyl compounds gives us a new and most versatile alcohol synthesis. Primary alcohols can be made through the reaction of an organometaUic reagent with formaldehyde (Fig. 16.62). Figure 16.62 also shows the shorthand form of the reaction, which emphasizes the synthetic utUity. 

Non-fluoride initiators have been employed satisfactorily as well, including Lewis bases (amines, amine A-oxides, carbonates and phosphates," LiOAc," " f-BusF ), Lewis acids," A-heterocyclic carbenes, or even without initiator in DMSO as solvent. The addition of TMSCF3 to carbonyl compounds in the presence of a chiral initiator allows the enantioselective preparation of trifluoromethyl alcohols. For this purpose, quaternary ammonium fluorides derived from cinchona alkaloids (1) have been employed, affording moderate (up to 51% ee) " to high enantioselectivities (up to 92% ee). Also, the corresponding bromides were used in combination with an external fluoride source (KF or TMAF, up to 94% ee) or with disodium (R)-binaphtholate (up to 71% ee), or simply a cinchonidine-derived ammoniumphenoxide (up to 87% ee). Moreover, the use of a chiral TASF derivative (2) has also been reported (up to 52% ee). ... 

Propargylic alcohols have been synthesized by the addition of alkynylsilanes to carbonyl compounds in a fluoride-catalysed procedure (Scheme 11), or under the influence of AICI3. ... 

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