Racemic diols

Bis(phe nylthiomethyl)dihydropyran, CSA, CHCI3, 54-93% yield. This dihydropyran can be used for the resolution of racemic diols or for regio-selective protection, which is directed by the chirality of the dihyropyran. Other 2,2 -substituted bisdihydropyrans that can be cleaved by a variety of methods are available, and their use in synthesis has been reviewed. ... 

Whereas the chiral TEMPO analog 87 was used to resolve racemic secondary alcohols, the D-fructose-derived ketone 88 [137] proved useful for oxidative resolution of racemic diols (Table 10.13) [138, 139], Persulfate in the form of Oxone, Curox, etc., served as the final oxidizing agent, and the dioxirane generated from the ketone 88 is the chiral active species. Because of the relatively low conversions (except for unsubstituted dihydrobenzoin) at which the ee stated were achieved, the method currently seems to be of less practical value. Furthermore, typically 3 equiv. ketone 88 had to be employed [138, 139]. 

As summarized in Schemes 12.9 and 12.10, kinetic resolution of propargylic [21] and allylic [22] alcohols work equally well. The DMAP-ferrocene hybrid 21c was also used for kinetic resolution of racemic diols and for the desymmetrization of meso diols [20]. These two applications are discussed in Section 13.3. 

When racemic diol 10 is crystallised from small solvents, an extraordinary type of inclusion compound is formed. These compounds, (10)4-(guest), have a unit cell in space group IA acd containing 32 molecules of the host diol and... 

KINETIC RESOLUTION OF DIOLS 5.5.1. Desymmetrization of racemic diols... 

In an enzymatic resolution approach, chiral (+)-tra .s-diol (60) was prepared by the stereoselective acetylation of racemic diol with lipases from Candida cylindraceae and P. cepacia. Both enzymes catalyzed the acetylation of the undesired enantiomer of racemic diol to yield monoacetylated product and unreacted desired (+)-trans-diol (60). A reaction yield of 40% and an e.e. of >90% were obtained using each lipase [104],... 

A Sharpless asymmetric epoxidation features in a synthesis of (S)-chromanethanol (15). In the key cyclisation step, the absolute configuration of the diol is retained by a double inversion (95SL1255). trans-6-Cyano-2,2-dimethylchroman-3,4-diol is obtained from the racemic diol with excellent optical purity by the stereoselective acylation using Candida cylindraceae lipase (95TA123). 

Reetz and coworkers tested catalysts for different reactions such as enantiose-lective acylation of a chiral secondary alcohol by lipases, the enantioselective ring opening of epoxides to non-racemic diols, and metathesis reactions [11, 12]. The two first examples are exothermic reactions and catalyst activity is revealed by hot spots in the IR image. The catalytic performance found by use of time-resolved IR-thermography correlated well with already known activity of the tested catalysts [11]. The metathesis reaction is particularly interesting, because it is the first example of the monitoring of endothermic reactions by means of an IR camera [12]. 

Figure 18.24. Microbial dynamic kinetic resolution of the racemic diol 65 to (5)-dioL...

In 1994, Hanessian and co-workers [50] reported the first examples of metal-free three-dimensional triple-stranded helicates through spontaneous self-assembly of chiral C2-symmetrical diols and chiral C2-symmetrical diamines. The initial observation resulted from the utilization of enantiopure C2-symmetrical vicinal trans-1,2-diaminocyclohexane [51,52] as ligands in the asymmetric dihydroxylations of olefins [53] and as reagents for asymmetric synthesis [54], When equimolar amounts of (5,5)-frfl x-l,2-diaminocyclohexane (28) and its (i ,i )-enantiomer (29) were individually mixed with (5,5)-frfl x-l,2-cyclohexanediol and heated in refluxing benzene, crystals of the respective supraminol complexes 28 30 and 29 30 were formed quantitatively (Scheme 12). This was the physical basis for the separation of racemic diols with tr[Pg.104]

Synthesis of Chiral Non-racemic Diols from (S.SJ-1,2,3,4-Diepoxybutane. 

Of the three types of racemates,11 conglomerate, racemic compound, and solid solution, 3-(1,2-dihydroxyethyl)-1,5-dihydro-3H-2,4-benzodioxepine shows melting point behavior characteristic of a racemic compound. The racemic diol is much higher melting than the enantiomerically enriched diol as shown in the Figure 1. Therefore the diol of lower ee precipitates first during recrystallization and the enantiomerically enriched diol remains in the mother liquor. High ee diol (97% ee) is then obtained upon recrystallization of this mother liquor. 

The enzyim o-galactose oxidase has been reported to oxidize some racemic diols with kinetic resolution to provide the corresponding hydroxy aldehydes with high enantiomeric excesses. A list of successful and unsuccessful substrates is given in Scheme 4. 

The use of enzymes for the enantioselective oxidation of prochiral (or racemic) diols has proved to be of significant synthetic interest. A range of simple racemic 1,2-diols proved to be good substrates for a system involving coimmobilized horse liver alcohol dehydrogenase (HLADH) and aldehyde dehydrogenase (AldDH) with NAD cofactor recycling. This produced enantiomerically pure a-hydroxycarbox-ylic acids (Scheme 12). 

Resolution of Racemic Diols and Amino Alcohols via Diastereomeric Borate Complexes... 

The racemic 2,3-diphenylbutane-1,4-diol 8, can be prepared via oxidative coupling of phenylacetic acid esters using TiCVEtaN10 followed by NaBHt/k reduction.11 We have examined the resolution of this valuable racemic diol using B(OH)3 and S-proline. The results are outlined in Scheme 4.llb... 

A complete study concerning a new class of supramolecular structures (supraminols) has been recently published. These supramolecular structures are formed by an enantiodifferentiating self-assembly between (If , 2f )-diaminocyclohexane and various trans-1,2-cyclohexane diols. An example is shown in eq 27. When racemic diols were used, a homochiral cristalline adduct is formed with an efficient kinetic resolution. 

The Katsuki-Sharpless asymmetric epoxidation of racemic diol ( )-496 (obtained by allylation of ( )-crotonaldehyde) gives, after chromatographic separation, the erythro-epoxidc (+)-497 (33% yield, >95% ee). Its urethane undergoes assisted epoxide ring opening under acidic conditions, providing a 10 1 mixture of araZ mg-carbonate (+)-498 and the nZ 6>-stereomer. Carbonate hydrolysis and subsequent ozonolysis generates D-olivose (Scheme 13.114). Asymmetric epoxidation of the kinetically resolved dienol (—)-496 (72%) leads to (—)-497... 

Recently, Osa and coworkers [502] have reported highly enantioselective electroca-talytic oxidation of racemic monoalcohols using a TEMPO-modified graphite felt electrode in the presence of (—)-sparteine. Optically almost pure i -isomeric alcohols remained unreacted. Highly enantioselective lactonization of racemic diols was also achieved by using the same TEMPO-modified electrode to give (S)-isometric lactones [503]. 

The reaction can also be run using catalytic amounts of a tin reagent which results in acylation of the least hindered alcohol or monoacylation of symmetrical diols is also possible. The use of a chiral tin reagent gives modest levels of kinetic resolution of racemic diols. ... 

---