Dioxolanes from diols

This and other fluorous acetal derivatives are prepared from diols bearing 13 or more F atoms to make them soluble in fluorinated hydrocarbons. They are prepared by the standard methods of heating the ketone with the diol in the presence of an acid such as TsOH or pyridinium tosylate. As with most 1,3-dioxanes and 1,3-dioxolanes, they can be cleaved with aqueous acid. ... 

Because of the thermodynamic stability of the ring, 1,3-dioxanes derived from aldehydes are formed more easily from 1,3-diols than 1,3-dioxolanes from 1,2-diols [7]. Substituents may affect the yield of the cyclic acetals. In a ruthenium-catalyzed reaction, an increase of yields was noted in the following order depending on the diol used (Figure 5.14) [8]. Glycerol usually gives mixtures of five- and six-membered acetals. 

Unsaturated substituents of dioxolanes 36-38 and dioxanes 39-41 are prone to prototropic isomerization under the reaction conditions. According to IR spectroscopy, the isomer ratio in the reaction mixture depends on the temperature and duration of the experiment. However, in all cases, isomers with terminal acetylenic (36, 39) or allenic (37, 40) groups prevail. An attempt to displace the equilibrium toward the formation of disubstituted acetylene 41 by carrying out the reaction at a higher temperature (140°C) was unsuccessful From the reaction mixture, the diacetal of acetoacetaldehyde 42, formed via addition of propane-1,3-diol to unsaturated substituents of 1,3-dioxanes 39-41, was isolated (74ZOR953). 

The initial investigation focused on the use of threitol-derived auxiliaries with various substituent groups on the dioxolane ring (Table 3.3). However, it became evident that the oxygen atoms in the substituents had a detrimental effect on selectivity. Comparison of the diastereoselectivities for the ketals 69-71, which contain Lewis basic sites in the substituents at the 1 and 2 positions, with those from simpler diol derived ketals 72-74 demonstrates the conflicting effects of numerous coordination sites. The simpler, diol-derived ketals provide superior results compared to the threitol derived ketals. The highest diastereoselectivity is observed in the case of the 1,2-diphenyl ethane-1,2-diol derived ketal 74. 

The alkenyl oxonium ion dienophiles generated from dioxolanes can be made diastereoselective by use of chiral diols. For example, acetals derived from anti-pentane-2,4-diol react under the influence of TiCl4/Ti(/-OPr)4 with stereoselectivity ranging from 3 1 to 15 1. 

Dioxolanes derived from sy -l,2-diphenylethane-l,2-diol react with dienes such as cyclopentadiene and isoprene, but in most cases the diastereoselectivity is low. 

Enantiomerically pure tetrahydro-l//-pyrrolo[2, l -acrylamides derived from proline (see Section 11.11.7.4), are versatile intermediates for the synthesis of natural products or drugs. Compound 86a was submitted to debromination with Bu3SnH followed by ring opening in KOH and further reduction with BHj to give diol 89 that was then easily transformed into (A)-4-(2,2,4-trimethyl-l,3-dioxolan-4-yl)-lT>utanol 90, a key intermediate for )-frontalin, <2002TA155>,... 

Alkenes from vie -diols.2 The 2-dimethylamino-l,3-dioxolanes 1, obtained by reaction of a 1,2-diol with N,N-dimethylformamide dimethyl acetal in quantitative yield, when treated with ethyldiisopropylamine (4 equiv.) and triflic anhy-... 

Unsymmetrical vicinal diols can be prepared from a three-component reaction of aldehydes, CO, and aminotroponiminate-ligated titanium dialkyl complexes. Solutions of Me2TiL,2 (L = N -dimethylaminolroponiminalc) react rapidly with CO at room temperature. Double methyl migration to CO produces an 2-acclonc complex which inserts the aldehyde to afford a titana-dioxolane and releases the unsymmetrical diol upon hydrolysis [65]. 

The crude product consists mainly of the desired product protection of the cis-2,3-diol occurs only to a minor extent. The major side product from the reaction is the 1,3-dioxolane, which can be slowly converted to the required product under thermodynamic equilibrating conditions i.e., further treatment of the dioxolane with... 

The groups of Burczyk, Takeda, and others have made thorough studies of cyclic acetals, such as 1,3-dioxolane (five-membered ring) and 1,3-dioxane (six-membered ring) compounds, illustrated in Fig. 13. They are typically synthesized from a long-chain aldehyde by reaction with a diol or a higher polyol. Reaction with a vicinal diol gives the dioxolane [40-42] and 1,3-diols yield dioxanes [43,44]. 

Fig.13 Preparation of 1,3-dioxolane surfactant (a) and 1,3-dioxane surfactant (b) from a long-chain aldehyde and a 1,2-and a 1,3-diol, respectively...

Ozone oxidation of the trans-decal in di of benzylidene 133 has been carried out (71). Under kinetically controlled conditions, it produces the axial benzoate 134 in preference to the more stable equatorial benzoate 135. Similar results were obtained with an analogous case derived from cholestane-2e,3e-diol. These results are essentially identical to those obtained by King and Allbutt (60, 62) in their study on the hydrolysis of dioxolane orthoesters and dioxolenium salts (cf. p. 82), and can therefore be explained in the same manner. These results further confirm that the oxidation of acetals by ozone produces an intermediate which behaves like the hemiorthoester tetrahedral intermediate which is formed in the hydrolysis of orthoesters. 

One recent publication from the group of Abu-Omar reports on a condensation reaction involving glycerol and furfural, both renewables, to produce dioxolanes, formally a dehydration reaction. Here, a cationic oxorhenium(V) oxazoline species is used as the catalyst for the formation of various 1,3-dioxalanes from furfural with diols or epoxides under mild conditions (Scheme 21). Especially interesting is the reaction of furfural with glycerol to obtain a 70 30 mixture of the corresponding 1,3-dioxolane and 1,3-dioxane in solvent-free conditions [125]. 

Romo et al. have used Lewis acids to catalyze the formation of a-silyl-/ -lactones in their synthesis of potential inhibitors of yeast 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) synthase <1998BMC1255>. In addition to various Lewis acid catalysts, a chiral promoter based on the chiral diol (l/ ,2R)-2-[(diphenyl)hydroxymethyl]cyclo-hexan-l-ol was introduced to the reaction in an attempt to improve the stereoselectivity. A variety of chiral 2-oxetanones were formed, with enantioselectivities ranging from 22% to 85%. Dichlorotitanium-TADDOL catalysts 113 and 114 have also been used in an attempt to encourage the stereoselective [2+2] cycloaddition of silyl ketenes and aldehydes (TADDOL = (—)-/ra r-4,5-bis(diphenyl-hydroxymethyl)-2,2-dimethyl-l,3-dioxolane), although this method only afforded 2-oxetanones in moderate yields and optical purity (Equation 41) <1998TL2877>. 

Rings containing unsaturation may be synthesized from fragments in higher oxidation states. l,3-Dioxolan-2-ylium cations are obtained directly from tertiary 1,2-diols and acyl cations in excellent yields (80ZOR183). The reaction, shown in equation (37), is limited to tertiary alcohols since steric hinderance prevents nucleophilic ring opening by the counterion. Another synthesis of limited scope is the addition of monothiobenzils to diaryl-diazomethanes (equation 38). The reaction also works for the dicarbonyl derivatives. 

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