Diols reaction with carbonyl compounds

Tetrahydrofuran itself can be opened using either the stoichiometric or the catalytic version of arene-promoted lithiation, but both cases need the activation by boron trifluoride. The catalytic reaction was performed by treating the solvent THF 324 with the complex boron trifluoride-etherate and a catalytic amount (4%) of naphthalene. The intermediate 325 was formed. Further reaction with carbonyl compounds and flnal hydrolysis yielded the expected 1,5-diols 326 (Scheme 95), which could be easily cyclized to the corresponding substituted tetrahydropyrans under acidic conditions (concentrated FlCl). 

Carbonyl compound adducts have also been lithiated with lithium in the presence of a catalytic amount of d -di-ferf-butylbiphenyl (DTBB) at —78 °C to provide, after reaction with carbonyl compounds, the corresponding 1,3-diols 138 (Scheme 37)141,142. 

Pentadiene-l,5-diols. Alkynylepoxides undergo reductive ring opening to generate allenylsamarium iodides, which, on reaction with carbonyl compounds, deliver the unusual products. 

Acetylene is condensed with carbonyl compounds to give a wide variety of products, some of which are the substrates for the preparation of families of derivatives. The most commercially significant reaction is the condensation of acetylene with formaldehyde. The reaction does not proceed well with base catalysis which works well with other carbonyl compounds and it was discovered by Reppe (33) that acetylene under pressure (304 kPa (3 atm), or above) reacts smoothly with formaldehyde at 100°C in the presence of a copper acetyUde complex catalyst. The reaction can be controlled to give either propargyl alcohol or butynediol (see Acetylene-DERIVED chemicals). 2-Butyne-l,4-diol, its hydroxyethyl ethers, and propargyl alcohol are used as corrosion inhibitors. 2,3-Dibromo-2-butene-l,4-diol is used as a flame retardant in polyurethane and other polymer systems (see Bromine compounds Elame retardants). 

The enantioselective hetero-Diels-Alder (HDA) reaction of carbonyl compounds with 1,3-dienes represents an elegant access to optically active six-membered oxo-heterocycles. Since the pioneering work of Rawal et al. in 2003 [55], the enantioselective HDA reaction catalyzed by diols (such as TADDOLs) has become a flourishing field of research [56]. 

The reaction of oxiranes with carbonyl compounds in the presence of Lewis acids is an efficient way of preparing 1,3-dioxolanes (81S501). The reaction, shown in Scheme 33, proceeds with inversion of stereochemistry of the oxirane. A diol does not appear to be an intermediate even in the presence of water. Many Lewis acid catalysts are effective, but the use of anhydrous copper(II) sulfate in an excess of the carbonyl compound as solvent probably offers the mildest conditions. Since the copper(II) sulfate is insoluble, the reaction appears to be truly heterogeneous in nature and the mixture must be well stirred (78JOC438). 

Brown, M. J., Harrison, T., Herrinton, P. M., Hopkins, M. H., Hutchinson, K. D., Overman, L. E., Mishra, P. Acid-promoted reaction of cyclic allylic diols with carbonyl compounds. Stereoselective ring-enlarging tetrahydrofuran annulations. J. Am. Chem. Soc. 1991,113, 5365-5378. 

An example is offered by the room temperature cholinium chlorozincate ionic liquid 22, an efficient catalyst for the protection of carbonyl groups with diols under solvent-free conditions (Strategy C). An equimolar mixture of a diol (1,2- to 1,5-diol) and a carbonyl compound is stirred at room temperature for 10-20 h in the presence of 22. Very high yields of acetals are reported and the catalyst is easily recovered and recycled. A typical reaction is reported in Figure 22. 

A similar oxidation of olefins with sodium bismuthate in acetic acid at elevated temperature (100°C) leads to a mixture of v/c-diol diacetate and carbonyl compound arising from oxidative cleavage, together with molecular oxygen and carbon dioxide [71KKZ1807]. In the absence of an olefin, sodium bismuthate works destructively on acetic acid to generate molecular oxygen, carbon dioxide, methyl acetate and a trace amount of methane, while the bismuthate is converted to bismuth acetate when the reaction is complete. The proposed mechanism is shown in Scheme 5.6. 

Neutral nucleophiles, such as Grignard reagents (R-Mg-Br), also react readily with carbonyl compounds, as shown in reaction (4.21). The hydroxide ion will also react as a nucleophile (reaction 4.22), but here the overall equilibrium lies well to the left so that only a few percent of the diol 7 is present in an aqueous solution of acetone. 

The above shown methodology has found wide application in organic synthesis. For instance, the reaction of intermediates (18) with carbonyl compounds gives 1,4-diols that undergo cyclization leading to tetrahydrofurans (20) under acidic conditions (Table 1). 

The ease of acetal formation depends largely on the structures of the reacting carbonyl compounds and alcohol.905 Primary alcohols react better than secondary or tertiary ones the ease of reaction of carbonyl compounds decreases in the order formaldehyde, aliphatic aldehydes,, / -unsaturated aldehydes, aromatic aldehydes, ketones acetone gives cyclic ketals very readily with 1,2- and 1,3-diols. 

As for the diols, the symmetric compounds have found most uses for nonsymmetric diols, a versatile synthesis via silyl ketones using the SAMP/RAMP methodology has been developedl5. Both enantiomers of the simplest symmetric diol, 2,3-butanediol (11), are often used in asymmetric synthesis, mostly for the formation of acetals and ketals with carbonyl compounds and subsequent reactions with acidic catalysts (Section D. 1.1.2.2.), Grignard reagents (Section D. 1.3.1.4.) and other carbanions (Sections D. 1.5.1., D. 1.5.2.4.), and diastereoselective reductions (Section D.2.3.3.). Precursors of chiral alkenes for cycloprotonations (Section D.1.6.1.5.) and for chiral allenes (Section B.I.), and chiral haloboronic acids (Section D. 1.1.2.1.) are other applications. The free diol has been employed as a chiral ligand in molybdenum peroxo complexes used for enantioselective epoxidation of alkenes (Section D.4.5.2.2.). 

This reagent can be prepared by reaction of 2-bromoallyl alcohol in ether with 2.5 eq. of f-butyUithium at -78 to 0°. It reacts with carbonyl compounds to form, after hydrolysis, unsaturated diols of type (1) in 65-75% yield. ... 

Polyacetals and polyketals are polyethers that form (1) through condensations of glycols with carbonyl compounds, (2) by exchange reactions of acetals or ketals, and (3) by additions of diols to dialkenes ... 

Percent product distribution Methylvinylketone (MVK) 49.0 1.1, metha-croleine (MAC) 44.3 1.6, 3-methyl-fiiran (MFU) 6.7 0.6 for isoprene mole fractions 400 ppm. The ratio of MVK to MAC under these conditions was 1.1 0.6. In the presence of NO the ratio is close to 1.4 [4]. Computer simulations based on our results for methylsubstituted 1-butenes showed that the observed [MVK]/[MAC] ratios are obtained with essentially equal probabilities for OH attack at the two double bonds of isoprene. This result contradicts predictions based on OH reaction rate coefficients for various methylsubstituted butenes [5]. Similar to results obtained for the 1-butenes, diols and hydroxy carbonyl compounds were found in small yields among the products. These are not included in the above product distribution because they are difficult to quantify. ... 

The vinylmagnesium derivatives (40), obtained by Cu -mediated anft-addition of Grignard reagents to primary a-acetylenic alcohols, can by hydrolysed to ( )-allylic alcohols (41) (Scheme 18) or, if = H, halogenated and then alkylated to yield (Z)-allylic alcohols (42)." Reaction of (40) with carbonyl compounds gives substituted but-2-ene-l,4-diols. ... 

The reaction of monodeprotonated [ C2]acetylene with carbonyl compounds has been exploited as a means of extension of the carbon chain of various terpenes and steroids by two [ " C]carbon atoms. In the simplest case, reaction of potassium [ C2]acetylide with steroid ketone 1 and subsequent acid catalyzed cleavage of the enol ether protecting group gave 17a-[ C2]ethynyltestosterone (2). The sequential addition of deprotonated [ C2]acetylene to carbonyl compounds opens access to symmetrical or unsymmetrical [2,3- C2]alkyn-l,4-diols is exemplified in the synthesis of all-tran -/3-[15,15 - C2]-carotene ([ C2]provitamin A). Thus, treatment of lithium [ C2]acetylide with terpene aldehyde 2 followed by double deprotonation of the resultant alkynol 4 and reaction with a second equivalent of 3 provided alkyne-l,4-diol 5 the requisite key intermediate. Subsequent acid-catalyzed dehydration of 5 followed by Lindlar s catalyst-mediated partial hydrogenation and photoisomerization afforded the final product". ... 

Thallium(III) acetate reacts with alkenes to give 1,2-diol derivatives (see p. 128) while thallium(III) nitrate leads mostly to rearranged carbonyl compounds via organothallium compounds (E.C. Taylor, 1970, 1976 R.J. Ouelette, 1973 W. Rotermund, 1975 R. Criegee, 1979). Very useful reactions in complex syntheses have been those with olefins and ketones (see p. 136) containing conjugated aromatic substituents, e.g. porphyrins (G. W. Kenner, 1973 K.M. Smith, 1975). 

Periodic acid oxidation (Section 15 12) finds extensive use as an analytical method m carbohydrate chemistry Structural information is obtained by measuring the number of equivalents of periodic acid that react with a given compound and by identifying the reaction products A vicinal diol consumes one equivalent of penodate and is cleaved to two carbonyl compounds... 

The oxidative cleavage of the central carbon-carbon bond in a vicinal diol 1, by reaction with lead tetraacetate or periodic acid, yields two carbonyl compounds 2 and 3 as products. 

Alkenes are reduced by addition of H2 in the presence of a catalyst such as platinum or palladium to yield alkanes, a process called catalytic hydrogenation. Alkenes are also oxidized by reaction with a peroxyacid to give epoxides, which can be converted into lTans-l,2-diols by acid-catalyzed epoxide hydrolysis. The corresponding cis-l,2-diols can be made directly from alkenes by hydroxylation with 0s04. Alkenes can also be cleaved to produce carbonyl compounds by reaction with ozone, followed by reduction with zinc metal. 

Nucleophilic addition of an alcohol to the carbonyl group initially yields a hydroxy ether called a hemiacetal, analogous to the gem diol formed by addition of water. HcmiacetaJs are formed reversibly, with the equilibrium normally favoring the carbonyl compound. In the presence of acid, however, a further reaction occurs. Protonation of the -OH group, followed by an El-like loss of water, leads to an oxonium ion, R2C=OR+, which undergoes a second nucleophilic addition of alcohol to yield the acetal. The mechanism is shown in Figure 19.12. 

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