2-substituted-1,2-diols

Other sterically more crowded and functionalized 2-substituted-1,2-diols are enzymatically acylated with high enantioselectivity as well (Scheme 56). In these cases selective acylation also occurs at the primary alcohol [244-246]. 

This reaction worked best with more highly substituted diols and give predominantly syn elimination. 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

In the Woodward-Modification, added water decomposes the above benzoxonium intermediate directly to a -substituted diol. 

It is often difficult to control the condensation reactions of silanediols so that only a single reaction occurs to give the disiloxanediol, but the sterically hindered ferrocenyl substituted diol 34 can be condensed to give 35 in good yield (equation 12). If 35 is subject to similar conditions but for 2 h at reflux temperature, then further condensation reactions... 

These observations suggest an interaction between the n electron cloud located at second and third carbon atoms of the diols and the lanthanide metal orbitals. Similar behaviour was observed in the mixed complexes of lanthanide /1-diketonates and the substituted diols [233],... 

The formation of diol-periodate esters is supported by physical evidence. The addition of ethane-1,2-diol to periodate solutions causes an initial rapid change in the uv absorption spectrum, followed by a slower change as the oxidation proceeds and lOJ is formed. Similar results are observed for other 1,2-diols except for highly substituted diols such as pinacol (Buist et al ). Buist and Bunton have shown that the cyclic periodate esters formed in alkaline solution from 1,2-diols and periodate can be detected by nmr. The initial fall in pH which occurs in the oxidations of ethane-1,2-diol and lightly substituted diols is also attributed to ester formation (Malaprade, Buist and Bunton ). Cyclic triesters, similar to the cyclic diesters formed from 1,2-diols, are formed from cyclic compounds containing the cis-l,2,3-triol system (Barker and Shaw , Dijkstra and from 1,2-0-isopropylidene-a-D-glucofuranose. In the latter case the presence of the triester has been demonstrated by nmr (Berlin and van Rudloff ). Monoesters of periodic acid have not been detected in any system, but they are postulated as intermediates in the formation of cyclic diesters from 1,2-diols (section 1.3.5). 

The optimum catalyst for the reaction of 175 and cyclopentadiene was generated in-situ from one equivalent of the diol and two equivalents of ethyl aluminum dichloride. Presumably this generates a Lewis acid with two dichloroalkoxy aluminum groups per molecule of catalyst. The catalyst generated from diol 181 and one equivalent of diethylaluminum chloride is not very active, possibly because here the catalyst is a di-alkoxy aluminum chloride. The highest induction was observed for a catalyst generated from the diamino substituted diol 187, which was prepared from tartaric acid. 

The acid-catalyzed hydrolysis of p-phenyl-substituted cyclohexene oxides 49a-d yields diols resulting from cis and "trans addition of water to the epoxide group (Scheme 14). It was initially reported that the cis/trans diol ratio correlates well with the electronic effect of the / -substituent, and varied from 7.5 93.5 for p-nitro-sub-stituted oxide 49d to 95.3 4.7 for p-methoxy-substituted epoxide 49a.56 58 Later work established that methoxy-substituted diols 50a and 51a underwent isomerization under the conditions of acid-catalyzed epoxide hydrolysis, and that the cis/ trans diol ratios for hydrolysis of 49a-c are quite similar.59... 

The selectivity can sometimes be rationalised on the basis of the mechanism illustrated in equation 14-45. The less substituted diol moiety, which is more reactive towards electrophiles in the diol, is also more prone to donate to tin in forming the dimer of the dioxastannolane, leaving the unassociated more substituted oxygen centre as the stronger nucleophile. However, the acylation reactions are complicated by the equilibration of the two possible isomers by the reaction 14-46, and by a suitable choice of reaction conditions, regioselectivities of <99% can often be obtained.41,94-96... 

T. Hudlicky et al. efficiently synthesized the prostaglandin PGE2 12 through an oxidative ring cleavage of the methyl-substituted diol 6 (R = CH ) 208, the vinyl... 

A comparative study of simple methyl-substituted diols (flow system or distillation, 448 K) showed that the reactivity of the diols increased with increasing substitution [36]. Under these conditions, however, especially when the distillation (batch) method is used, a secondary transformation occurs-the product car-... 

The pinacol rearrangement of simple methyl- and phenyl-substituted diols in the presence of different montmorillonites was examined by Gutierrez and Ruiz-Hitzky [33,37-39]. The transformations were performed in dry media without solvent, with the reacting diols intercalated into the interlamellar space of the montmorillonites. High catalyst/diol ratios (> 5) and mild reaction conditions were usually used. 

Mephenesin and meprobamate are substituted diols. Other compounds of the same class with muscle relaxant and sedative properties include phenaglycodol IX) and carisoprodol XI). They have little clinical usefulness. 

In many instances, the tetranaphthyl-substituted diol, the preparation of which is described here, gave the most effective chiral titanium catalysts. Three examples are the nucleophilic addition of diethylzinc to aldehydes (eq 1),10 the Diels-Alder reaction of 3-crotonoyl-1,3-oxazolidin-2-one to cyclopentadiene (eq 2),7 and the ring opening of a meso anhydride to a half ester (eq 3).11... 

A more refined model of stereoselectivity has been proposed on the basis of the X-ray structure of PPL and the stereoselectivity toward several aryl-substituted diols. This model proposes an important tt-tt stacking interaction between the aryl... 

A remarkable application of the stannylation procedure is the organotin-mediated monoacylation of diols with reversed chemoselectivity, by which monoesterification of unsymmet-rically substituted diols at the most substituted hydroxyl group can be achieved with acyl chlorides [60], In the reported mechanism [61], this unusual reversal of chemoselectivity rests on a fast intramolecular transesterification equilibrium in which the dibutylstannylene acetal plays the double role of reagent and catalyst. The knowledge of the reaction mechanism allows for adjustment of experimental conditions to achieve remarkable selective level which can be higher than 99% using appropriate reagents (Scheme 4). 

The creation of diastereoisomeric molecules which are epimeric at phosphorus presents no fundamental difficulties. Such molecules are readily available by means of reactions between the dichlorides RP(=Z)Cl2 (Z = O, S or Se) and an appropriate chiral difunctional compound. Many reactions that lead to such products were indicated in the previous chapter in connection with the synthesis of enantiomers of, particularly, (l-aminoalkyl)phos-phonic acids and related compounds. With regard to the preparation of diastereoisomeric thio- or seleno-phosphoryl compounds epimeric at phosphorus, the chiral reactants first used were modified carbohydrates and, less successfully, simple mono- or di-substituted diols. The latter provided simple monocyclic 1,3,2-dioxaphospholanes and 1,3,2-dioxaphosphorinanes which could provide (a) chiral centre(s) on (a) ring carbon atom(s), but also generated compounds epimeric at phosphorus their inconvenience often lay in lack of availability of cheap starting materials. In the case of the carbohydrates, the substrates were readily available from cheap starting materials thus, methyl 2,3-di-(9-methyl-... 

A collection of results obtained with the most effective catalyst systems is summarized in Figure 6.4. Noteworthy examples include the oxidation of a-aminoalcohols with no loss in enantiopurity and the oxidation of cis-allyhc alcohols without Z E isomerization. Stahl also demonstrated the chemoselective oxidation of primary diols to form lactones [22]. While ABNO provides efficient oxidation of symmetric diols, TEMPO discriminates between subtle steric differences in nonsymmetrical substituted diols. Cu/nitroxyl catalysts have also been applied to a variety of tandem reactions [23], perhaps the most noteworthy of which is the conversion of primary alcohols to nitriles via in situ condensation of ammonia with the aldehyde and subsequent dehydrogenation of the primary imine to the nitrile (Figure 6.5) [24]. 

Several useful one-pot procedures employing the reaction of tosyl chloride with vicinal diols have been used to form epoxides. Treatment of variously substituted diols with 1 equiv of tosyl chloride and sodium hydroxide in monoglyme provides access to a variety of 1-alkynyloxiranes (R and/or being terminal or substituted alkynes) in moderate to good yield (eq 15). ... 

Phase-transfer catalysis has also been successfully employed to achieve epoxidation. A variety of cyclic frawi -substituted diols in dichloromethane were treated with a 50% aqueous solution of sodium hydroxide in the presence of the phase-transfer catalyst... 

Heck arylation of allylic diols, with iodobenzene in the presence of potassium carbonate, resulted in phenyl-substituted diols. A selective /8-hydride elimination in a chelated ring intermediate may be responsible for this outcome (the authors suggest de-protonated cr-intermediates) (Scheme 30). Arylation of an aUylic substrate lacking the ho-moallylic hydroxy group under otherwise identical conditions furnished a mixture of products, suggesting that the aforementioned hydroxy group has an impact on the hydride elimination. 

---