Additions of Alcohols and Carboxylates

Intermolecular Additions of Alcohois and Carboxylates The intermolecular oxidations of olefins with alcohols as nucleophile typically generate ketals, whereas the palladium-catalyzed oxidations of olefins with carboxylic acids as nucleophile generates vinylic or allylic carboxylates. As a result, many of the oxidations with alcohols have been conducted with diols to generate stable cyclic acetal products. Both types of oxidations have been conducted on large industrial scale, and vinyl acetate is produced from the oxidative reaction of ethylene with acetic acid in the gas phase over a supported palladium catalyst.  

This divergent oxidative reactivity of alcohols and carboxylic acids with olefins is illustrated in Equation 16.103. Bofli reactions generate products from p-hydrogen elimination of an alkoxyalkyl or acetoxyalkyl complex. However, the vinyl ether product generated by p-hy-drogen elimination undergoes reaction with a second equivalent of alcohol to form the acetal in a process catalyzed by the acidic medium or the action of palladium(II) as Levris add. 

Simple examples of the reactions of olefins with diols are shown in Equations 16.104 and 16.105. Reactions of alkenes typically generate ketals, whereas reactions of olefins bearing electron-withdrawing groups, such as those in acrylates or acrylonitrile, tend to form acetals. This regioseJectivity is shown by the reactions of butene and 

Intermediates that control the selectivity of the Wacker-type oxidations of olefins. 

Examples of the oxidative reactions of olefins with carboxylic acids are shown in Equations 16.107-16.109. These examples illustrate the selectivities of the oxidations of ethylene, acylic alkenes, and cyclic alkenes. The reactions of alkenes with carboxylic adds generate either vinylic esters or allylic esters. 

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Copper The catalytic activity of copper(II) triflate for cyclizations of alkenols or intermolecular additions of alcohols and carboxylic acids to norbomene has been reported [62, 63]. In dioxane at 80°C, high conversions were achieved at prolonged reaction times, and those were superior to those obtained with Lewis acids such as Yb(OTf)3, though the latter also displayed catalytic activity [62]. In a control experiment with triflic acid (10 mol%) only little product (29%) resulted with low stereoselectivity. However, it is now clear that this control experiment was flawed, as too much triflic acid and overly long reaction times had been applied. The previously mentioned study by Carpentier and coworkers on copper triflate catalyzed hydroaUcoxylations has established that Cu(OTf)2 decomposes to CuOTf and triflic acid when heated in organic solvents [50]. Triflic acid is catalytically active in hydroaUcoxylation at levels down to 0.1 mol%, if a polymerization inhibitor is present to prevent consumption of the olefinic substrate. Indeed, Cu (OTf)2 is an excellent reagent for releasing small amounts of triflic acid in this case, because the coreleased CuOTf acts as polymerization inhibitor for the acrylic substrate (Scheme 12) [50]. Other metal triflates like Sc(OTf)3 or Yb(OTf)3 displayed catalytic activity at the 1 mol% level in the reaction of Scheme 12. Additional experiments were presented to support the conclusion that triflic acid is the actual catalyst in this and other Lewis acid catalyzed hydroalkoxylations [50]. 

Yang C-G, Reich NW, ShiZ, He C (2005) Intramolecular additions of alcohols and carboxylic acids to inert olefins catalyzed by sUver(I) triflate. Org Lett 7 4553-4556... 

Addition of Alcohols, Amines, Carboxylic Esters, Aldehydes, and so on. Hydro-acyl-addition, and so on. 

Ethyl 2-amino-A -dihydrothiopyran-3-carboxylate has been included in a spectroscopic study of the protonation of heterocyclic enamines, and the acid-catalysed addition of alcohols and thiols to A -dihydrothiopyran has been investigated. ... 

Application of AA vapour has been shown to lead to major changes in fruitripening processes in non-climacteric and climacteric fruit (Fidler 1968). Yamashita et al. (1975,1976) showed that intact strawberries were able to synthesize carboxylic esters on addition of alcohols and acids or aldehydes and acids. In... 

If a reaction is catalyzed by a proton add, a metal-catalyzed version may also be possible. Such is the case for addition of alcohols or carboxylic acids to alkenes and alkynes catalyzed by silver salts such as AgOTf. In hidden acid catalysis, the metal may liberate free protons that are the true catalyst. Careful control experiments are needed to test this possibility. 

Oxidative addition of the O-H bond to transition metal complexes gives hydrido(hy-droxo), hydrido(alkoxo) or hydrido(carboxylato) complexes (Eq. 6.1), but web-characterized complexes obtained as primary products from the reaction of the compound, XO-H (XO-H = water, alcohol, and carboxylic acid) with late transition metals are quite rare [1]. Furthermore, the crystal stractures of very few complexes of this type have been reported. In this section we will survey late transition metal complexes resulting from activation of water, alcohol, and carboxylic acid. 

In the sixth chapter the activation of O-H bonds of water, alcohols and carboxylic acids, and their addition to multiple bonds is reported. Since the formally oxidative addition of ROH gives rise to hydrido(hydroxo) complexes, [MH(OR)Ln] which are postulated as intermediates in many important reactions (water gas shift reaction, Wacker-chemistry, catalytic transfer hydrogenations etc.) the authors of this chapter,... 

Addition of nucleophilic solvents such as alcohols and carboxylic acids can be effected by using strong acids as catalysts.10... 

The nucleophiles that are used for synthetic purposes include water, alcohols, carboxylate ions, hydroperoxides, amines, and nitriles. After the addition step is complete, the mercury is usually reductively removed by sodium borohydride, the net result being the addition of hydrogen and the nucleophile to the alkene. The regio-selectivity is excellent and is in the same sense as is observed for proton-initiated additions.17... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

The first commercial Fischer-Tropsch facility was commissioned in 1935, and by the end of the Second World War a total of fourteen plants had been constructed. Of these, nine were in Germany, one in France, three in Japan, and one in China. Both German normal-pressure and medium-pressure processes (Table 18.1) were employed. The cobalt-based low-temperature Fischer-Tropsch (Co-LTFT) syncrude produced in these two processes differed slightly (Table 18.2), with the product from the medium-pressure process being heavier and less olefinic.11 In addition to the hydrocarbon product, the syncrude also contained oxygenates, mostly alcohols and carboxylic acids. 

The most characteristic and useful reaction is the dimerization with incorporation of certain nucleophiles. It is well-known that simple olefins coordinated by Pd2+ compounds undergo nucleophilic substitutions [Eq. (9)] or addition reactions [Eq. (10)] (16, 17). Water, alcohols, and carboxylic acids are typical nucleophiles which attack olefins to form aldehydes, ketones, vinyl ethers, and vinyl esters. 

The nucleophilic addition of alcohols [130, 204-207], phenols [130], carboxylates [208], ammonia [130, 209], primary and secondary amines [41, 130, 205, 210, 211] and thiols [211-213] was used very early to convert several acceptor-substituted allenes 155 to products of type 158 and 159 (Scheme 7.25, Nu = OR, OAr, 02CR, NH2, NHR, NRR and SR). While the addition of alcohols, phenols and thiols is generally carried out in the presence of an auxiliary base, the reaction of allenyl ketones to give vinyl ethers of type 159 (Nu = OMe) is successful also by irradiation in pure methanol [214], Using widely varying reaction conditions, the addition of hydrogen halides (Nu= Cl, Br, I) to the allenes 155 leads to reaction products of type 158 [130, 215-220], Therefore, this transformation was also classified as a nucleophilic addition. Finally, the nucleophiles hydride (such as lithium aluminum hydride-aluminum trichloride) [211] and azide [221] could also be added to allenic esters to yield products of type 159. 

Cation-exchanged bentonites have been shown to be effective catalysts for addition of water, alcohols, and carboxylic acids to carbon-carbon double bonds under relatively mild conditions (75,... 

In this section, you were introduced to some of the main types of organic reactions addition, substitution, and elimination reactions oxidation and reduction and condensation and hydrolysis reactions. In the next section, you will take a close look at each type of reaction. You will find out how organic compounds, such as alcohols and carboxylic acids, can react in several different ways. 

The stoichiometric composition of the halogenoborane complexes is 1 1, as a rule. However, in some cases, 2 1 and 4 1 complexes are also obtained (Table 4). In the latter instances additional ligands are bonded to the 1 1 complex through hydrogen bonds.2,11 55 With ammonia only the 1 1 complex is stable, whereas (H20)2-BF3 is more stable than H20-BF3. BF3 produces 2 1 complexes of similar stability with alcohols and carboxylic acids.2,55,57 At low temperatures some tertiary amines give complexes with halogenoboranes and complexes of... 

Acid-catalyzed addition of water and alcohols to 4/f-chromenes gives the expected products as predicted by Markovnikov s rule (56JCS4785) an anti-Markovnikov addition of methanol followed by the reintroduction of a double bond in the alternative position gives an overall effect of substitution of hydrogen by methoxy and this is effected by treating methyl 2if-chromene-3-carboxylate (166) with triphenylmethyl perchlorate and addition of methanol to the resulting benzopyrylium salt (167) (72CR(C)(274)650). 

The first step in the overall synthetic scheme (Scheme 6) is the condensation of an appropriate carboxylic acid with trifluoroacetaldehyde. The carboxylic acid is chosen to impart specificity for the target enzyme. In one example,[28 the dianion of cyclohexanepropanoic acid (29) was formed by the addition of LDA and then quickly condensed with trifluoroacetaldehyde to form the p-hydroxy acid 30 as a racemic mixture of erythro- and threo-isomers. The p-hydroxy acid 30 is then protected with TBDMSOTf forming 31. Diphenyl phosphorazidate, TEA, and benzyl alcohol were then utilized in a Curtius rearrangement of the protected alcohol 31, which proceeds through an isocyanate intermediate that yields the protected amino alcohol 32 upon reaction with benzyl alcohol. In order for this step to occur at an appreciable rate, a second equivalent of triethylamine had to be added. The amino alcohol 32 was then deprotected and coupled with Boc-Phe-Leu-OH to give the trifluoromethyl alcohol 33, which was oxidized to the corresponding trifluoromethyl ketone 34 as a 1 1.2 mixture of diastereomers using the Dess-Martin periodinane procedure. Thus far, the compound shown in Scheme 6 is the only compound that has been synthesized by this method, but it is reasonable to assume that many other similar fluoro ketones can be produced by this scheme. 

Diphenyl diselenide is an especially useful co-reagent with [bis(acetoxy)-iodo]benzene. For example, the BAIB/PhSeSePh (2 1) combination has been employed for trans, Markovnikov additions of PhSeOAc and PhSeOH to alkenes [35]. Such formal additions appear to be regulated by seleniranium intermediates, and were extended to intramolecular cyclizations of olefinic alcohols, carboxylic acids, and / -dicarbonyl compounds (Scheme 12). 

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