Diols cyclic acetals from

Reaction is acid catalyzed Equilibrium constant normally favorable for aide hydes unfavorable for ketones Cyclic acetals from vicinal diols form readily... 

Gross and Dicesare43 have described a preparation of cyclic acetals from vicinaldiols and methylene chloride using PTC. The method is of special interest in carbohydrate chemistry where these acetals are usually obtained under acidic conditions by the reaction of the diol with an aldehyde. 

This type of reaction attracted broad interest when it was discovered that high regioselectivity can also be effected with organoaluminum compounds and other nucleophiles in the presence of Lewis acids and that by employing chiral cyclic acetals (from optically active 1,2- or 1,3-diols) diastereoselective transformations can be realized. - Such reactions are synthetically very valuable when considering that the overall process represents an enantioselective Michael addition, where the chiral auxiliary can be recycled (Scheme 39). ... 

DMAP-Initiated Protecting Group Strategies. DMAP has also been utilized as a key component in several protecting group strategies. The formation of cyclic acetals from 1,2-diols and alkyl propynoates in the presence of DMAP has been demonstrated. These acetals are stable to acid-catalyzed hydrolysis, unlike other acetals, and methanolysis. These acetals can be deprotected by heating in neat pyrrolidine. 

Formals. Paraformaldehyde added at room temp, to a soln. of 2,2,2-tribromo-ethanol in 89.6%-H2SO, and the product isolated after 0.5 hr. -> bis- (2,2,2-tri-bromoethyl) formal. Y 87%. — Acetal formation by the usual methods is difficult to achieve with negatively-subst. alcohols. F. e., also cyclic acetals from negatively-subst. diols, s. K. G. Shipp and M. E. Hill, J. Org. Ghem. 31, 853 (1966). 

This reaction looks much like the formation of a cyclic acetal from a 1,2-diol and a ketone. The intermediate breaks down to form the two carbonyl compoimds. As you can see from the mechanism (Fig. 16.74), only vicinal diols can imdeigo this cleavage reaction. 

In Section 17.9 we explored the use of diols to protect carbonyl groups. Entry 5 shows how carbohydrates can function as the diol component in forming a cyclic acetal from benzaldehyde, thereby protecting two of the carbohydrate s hydroxyl groups. This is yet another example of acetal formation, in this case involving the aldehyde group of benzaldehyde and the C-4 and C-6 hydroxyl groups of the carbohydrate. 

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

Diols that bear two hydroxyl groups m a 1 2 or 1 3 relationship to each other yield cyclic acetals on reaction with either aldehydes or ketones The five membered cyclic acetals derived from ethylene glycol (12 ethanediol) are the most commonly encoun tered examples Often the position of equilibrium is made more favorable by removing the water formed m the reaction by azeotropic distillation with benzene or toluene... 

In 1970, it was disclosed that it is possible to achieve the conversion of dimethylformamide cyclic acetals, prepared in one step from vicinal diols, into alkenes through thermolysis in the presence of acetic anhydride." In the context of 31, this two-step process performs admirably and furnishes the desired trans alkene 33 in an overall yield of 40 % from 29. In the event, when diol 31 is heated in the presence of V, V-dimethylforrnamide dimethyl acetal, cyclic dimethylformamide acetal 32 forms. When this substance is heated further in the presence of acetic anhydride, an elimination reaction takes place to give trans olefin 33. Although the mechanism for the elimination step was not established, it was demonstrated in the original report that acetic acid, yV, V-dimethylacetamide, and carbon dioxide are produced in addition to the alkene product."... 

Smaller aldehydes form cyclic acetal-type oligomers readily in aqueous conditions.60 Diols and polyols also form cyclic acetals with various aldehydes readily in water, which has been applied in the extraction of polyhydroxy compounds from dilute aqueous solutions.61 E in water was found to be an efficient catalyst for chemoselective protection of aliphatic and aromatic aldehydes with HSCH2CH2OH to give 1,3-oxathiolane acetals under mild conditions (Eq. 5.7).62... 

Acetal handle 78 synthesized from Merrifield resin and 4-hydroxy-benzaldehyde was applied to the solid-phase synthesis of carbohydrates and 1-oxacephams (Scheme 41) [90]. For the latter, a 1,3-diol was initially anchored to the support to form a cyclic acetal. A ring opening reaction with DIBAL generated a resin-bound alcohol which was converted to the corresponding triflate for A-alkylation with 4-vinyl-oxyazetidin-2-one. A Lewis acid catalyzed ring closure released 1-oxa-cephams from the support. 

The hydroformylation of acrolein cyclic acetals has received considerable attention in the recent patent literature as a route to 1,4-butanediol (76-52). This diol is a comonomer for the production of polybutylene terephthalate, an engineering thermoplastic. The standard method for its manufacture has been from acetylene and formaldehyde, as shown in Eqs. (37) and (38) ... 

Cyclic acetals derived from diols and o-nitrobenzaldehyde produce hydroxynitrosobenzoates upon irradiation (see Scheme 26). Early studies of this reaction demonstrated that acetals involving carbohydrates and o-nitrobenzaldehyde experience facile, photochemical... 

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]. 

The 6,7-dihydro-5/f -1,4-dioxepin (266) has been prepared (54CR(38)982). and more recently it has been shown that the 2,3-dihydro-5jF/-l,4-dioxepins (263) and (265) can be produced from 1,4-dioxine-halocarbene adducts (264), either by heating under reflux in xylene or by treatment with bases. The allylic chlorine atom in (263) is readily substituted by alkoxide or cyanide ions (77ZC331, 76UKZ968). Saturated rings of type (267) have been prepared by the treatment of cyclic acetals of ethane-1,2-diol with vinyl ethers in the presence of boron trifluoride, and l,4-dioxepan-5-one (268) has been prepared by the reaction of bromoform and silver nitrate with aqueous dioxane (60AG415). 

C of the acetal and the Lewis acid. Enantiomerically pure cyclic acetals 49 deriving from chiral diols open a route to adducts 50, which can be successively elaborated to chiral /9-hydroxyesters upon oxidation of the alcoholic group followed by alkaline elimination (equation 33). 

An alternative strategy for preparation of monoacylated 1,2- and 1,3-diols is oxidative deavage of cyclic acetals prepared from a diol and an aliphatic or aromatic aldehyde (Scheme 10.7). For this purpose the required acetal does not need to be isolated, but can be generated in situ [25]. Acetals prepared from strongly electrophilic aldehydes, for example nitrobenzaldehydes, will, however, usually be difficult to oxidize (and to hydrolyze). 

Generally intramolecular reactions are easier than intermolecular reactions entropy being a major factor. If you want to make an acetal from a ketone (chapter 6) it is better to use a diol 47 rather than, say methanol. The equilibrium is in favour of the cyclic acetal 48 but not in favour of the methyl acetal 46. Two molecules—one of each—go into 48 but three—two alcohols and one ketone—go into 46. Entropy is a thermodynamic factor. 

During the time frame covered by this chapter, stannanes have been reported to have been involved in radical chemistry not involving the more traditional functionalities. For example, Marzi and coworkers reported that the reduction of cyclic thionocarbonates (e.g. 82) with BusSnH under standard radical conditions affords cyclic acetals that can then be further transformed into 1,2-diols (equation 57)219. This transformation represents a new approach to the protection of these diols. Zehl and Cech described the use of Bu3SnH in the reduction of azide (83) to the corresponding amine (equation 58)305, while Hanessian and his associates reported the Ph3SnH-mediated free-radical reduction of the tertiary oxalate (84) (equation 59)309. This transformation represents a departure from the more typical reduction of a pyridinethioneoxycarbonyl (PTOC) oxalate ester321. 

Cyclic acetals like this are more resistant to hydrolysis than acyclic ones and easier to make—they form quite readily even from ketones. Again, we have entropic factors to thank for their stability. For the formation of a cyclic acetal, two molecules go in (ketone plus diol) and two molecules come out (acetal plus water), so the usually unfavourable AS0 factor is no longer against us. And, as for hemi-acetals (see the explanation above), equilibrium tends to lie to the acetal side because the intramolecular ring-closing reaction is fast. 

Chiral diols have also been prepared starting from meso-compounds [68-71]. Since meso-compounds are, in essence, symmetric molecules, the same applies as for the other symmetric starting materials. Indeed, this is exactly what was found Even though the stereocenters of the protected heptane tetrol are far away from the ester groups that are to be hydrolysed stereoselectively, this is what happens [69, 70]. The high selectivity is partly due to the fact that the secondary alcohol groups are protected as a cyclic acetal, giving additional structural information to the enzyme (Scheme 6.20 A). A cyclic acetal also provides additional structural information in the enantioselective hydrolysis of a pentane tetrol derivative (Scheme 6.20 B) [71]. In both cases Pseudomonas fluorescens lipase (PFL) proved to be the enzyme of choice. 

---