Meso-l,2-diols

The new heterocyclic derivative 130 has been shown to be an efficient chiral auxilliary for asymmetric desymmetrization of cyclic meso-l,2-diols via diastereoselective acetal cleavage . 

This transformation to chiral products is also applicable to 2-alkyl-1,3-propanediols and meso-l,2-diols. 

The desymmetrisation of meso-l,2-diols has been achieved by Oriyama using enantiopure diamines including (12.103),and also atropisomeric 4-aminopyridines. Metal-based catalysts have also been used to good effect in... 

Scheme 13.8 One-pot des5nnmetrisation of meso-l,2-diols through acylation and oxidation.

Acetal Formation Involving C -Symmetric Bis-sulfoxide and meso-l,2-Diols (Step 1). Acetalization of meso-1,2-diols with this reagent should be conducted with TMSOTf and 2,6-lutidine in dichloromethane below 4 °C. Higher temperatures and prolonged reaction times cause undesirable racemization and decomposition of the reagent. When the reactivity of meso-1,2-diols with the chiral auxiliary is low, acetalization using the mono-TMS ether of meso-diols and TMSOTf is recommended. ... 

In another context, Cao and Qu showed that an enantioselective acylation catalysed by a chiral thioamide modified 1-methylhistidine methyl ester (Scheme 2.19) in combination with a DABCO-mediated racemisation of the substrate led to the efficient dynamic kinetic resolution (DKR) of meso-1,2-diol monodichloroacetates. As shown in Scheme 2.19, both cyclic and acyclic meso-l,2-diol monodichloroacetates could be transformed to the corresponding enantiomerically enriched (15, 2R)-heterosubstituted diol esters in good yields and moderate enantioselectivities of up to 74% ee. 

Scheme 2.19 DKR of meso-l,2-diol monodichloroacetates catatysed by a chiral thioamide and DABCO.

Buta-1,3-diene (10.101, Fig. 10.24) is a gaseous chemical used heavily in the rubber and plastics industry, the presence of which in the atmosphere is also a concern. Butadiene is suspected of increasing the risks of hematopoietic cancers, and it is classified as a probable human carcinogen. Butadiene must undergo metabolic activation to become toxic the metabolites butadiene monoepoxide (10.102, a chiral compound) and diepoxybutane (10.103, which exists in two enantiomeric and one meso-form) react with nucleic acids and glutathione [160 - 163], as does a further metabolite, 3,4-epoxybutane-l,2-diol (10.105). Interestingly, butadiene monoepoxide is at least tenfold more reactive than diepoxybutane toward nucleic acids or H20. Conjugation between the C=C bond and the oxirane may account for this enhanced reactivity. 

The chiral substrate trans- stilbene oxide (10.121) behaved differently, yielding meso-l,2-diphenylethane-l,2-diol (meso-10.122) [183], This means that, in both enantiomeric substrates, the enzyme does not discriminate between the two oxirane C-atoms, bringing about inversion of configuration at the C-atom attacked. Interestingly, the various stereoisomers of 1,2-diphenylethane-l, 2-diol can be interconverted metabolically by alcohol/ketone equilibria catalyzed by alcohol dehydrogenases. 

For further contributions on the dia-stereoselectivity in electropinacolizations, see Ref. [286-295]. Reduction in DMF at a Fig cathode can lead to improved yield and selectivity upon addition of catalytic amounts of tetraalkylammonium salts to the electrolyte. On the basis of preparative scale electrolyses and cyclic voltammetry for that behavior, a mechanism is proposed that involves an initial reduction of the tetraalkylammonium cation with the participation of the electrode material to form a catalyst that favors le reduction routes [296, 297]. Stoichiometric amounts of ytterbium(II), generated by reduction of Yb(III), support the stereospecific coupling of 1,3-dibenzoylpropane to cis-cyclopentane-l,2-diol. However, Yb(III) remains bounded to the pinacol and cannot be released to act as a catalyst. This leads to a loss of stereoselectivity in the course of the reaction [298]. Also, with the addition of a Ce( IV)-complex the stereochemical course of the reduction can be altered [299]. In a weakly acidic solution, the meso/rac ratio in the EHD (electrohy-drodimerization) of acetophenone could be influenced by ultrasonication [300]. Besides phenyl ketone compounds, examples with other aromatic groups have also been published [294, 295, 301, 302]. 

Incubation of the (1R,2R) diol 25 over a shorter time period of 4 days gave a mixture of the meso cis diol 26 (26%) and the trans diol 25 RR/SS 76 26) showing conversion over to the (1S,2S) diol. As with the previous examples, no conversion was observed when using the S,S diol 25 as a substrate. Although no intermediate a-hydroxyketone was observed for this substrate we proposed the operation of at least two dehydrogenase enzymes, DH-1 and DH-2, catalysing the (i )-selective oxidation and (S)-selective reduction respectively (Scheme 12). Incubation of cis cycloheptan-l,2-diol afforded only the (S)-2-... 

Obviously with the indan-l,2-diol substrates there is no symmetrical meso intermediate which makes interpretation of the mechanism more difficult. In both the cyclohexan-l,2-diol and the indan-l,2-diol series the trans diols react faster and cis diols (both enantiomers for indandiol) are seen as intermediates. The (IS,2R) cis indandiol 29 is faster reacting and on incubation of the racemate only a very small trace of the R,R)-trans 28 isomer is observed. 2-Hydroxyin-dan-1 -one 30, an observed intermediate in these biotransformations, undergoes kinetic resolution when incubated as a racemic substrate. The faster reacting enantiomer is reduced to the faster reacting cis (lS,2i )-indan-l,2-diol 29 which is subsequently transformed into both trans diols and ultimately the (S,S)-iso-mer. Current work is focussing on determining the absolute configuration of the intermediate a-hydroxyketone 30. 

Nitrogen-coordinated pentacoordinate complexes have been used as stereoselective reducing agents in the preparation of erythro-(meso)- 1,2-diols from diketones and a-hydroxyketones109. The reducing agent was the (l-naphthylamino-8)trihydridosilane 92e. After formation of the dioxo chelate from the diketone (equation 32), the diol was obtained from the pentacoordinate silicon complex by reduction with LiAlILt. 29 Si NMR spectroscopy was used for the product-ratio analysis in this reaction, which was found to yield primarily the erythro diols. 

An alternative approach from a noncarbonyl precursor starts from l,2-bis(methylamino)ethane-l,2-diol dihydrochloride 80, and is used to prepare racemic and meso-bidiaziridine 81 (Scheme 28) <2004RCB641>. 

Ole/m synthesis, Eastwood ei al. have reported a new method for conversion of W -diols into alkenes. For example, rut-1,2-diphenylethane-l,2-diol (1) is heated with N,N-dimcthylformamide dimethyl acetal to give 2-dimethylamino-/rani -4.5-diphenyl-1,.3-dioxolanc (2). When this dioxolane is heated with acetic anhydride at 165-180° rruns-stilbene (3) is formed in 80% yield. Similarly, meso-l,2-diphenylethane-l,2-diol is converted into m-stilbene (75%) and a trace of truns-stilbene if the elimination... 

Values of the rate coefficients and k have been determined for ethane-l,2-diol andmethyl-substituted ethane-l,2-diols (Buisteta/. ). The general effect of methyl substitution is to decrease k . For meso- and ( )-butane-2,3-diols the values of kf are practically identical, although the equilibrium constant for forming the diester is much larger for the latter. This result suggests that formation of a monoester as an intermediate is rate determining, viz. 

Later, Kiindig and coworkers extended the substrate scope of catalysts 24 and 25 from weso-l,4-diol complexes such as 26 to simple meso- 1,2-diols 28 [31c], In the presence of 2 mol% of the catalyst, all of the tested cyclic and acyclic 1,2-meso-diols, except for substrates incorporating phenyl groups, were efficiently desymmetrized to... 

Such an A2 mechanism (A stands for acid, 2 indicates a bimolecular rate-determining step) results in a stereospecific reaction. Thus ( )-butane-2,3-diol is formed from cz.s-2,3-dimethyloxirane and meso-butane-2,3-diol from ra 5-2,3-dimethyloxirane. The oxirane obtained by epoxidation of cyclohexene is ra .s -cyclohexane-l,2-diol. 

Also, the Schreiner group published in 2009 a desymmetrisation approach of meso-(cyclo)alkane-l,2-diols applying the lipophilic peptide catalyst 7 (Scheme 13.8) already successfully used in kinetic resolution processes (Scheme 13.5) as previously described. The desymmetrisation step was combined in one pot with a direct TEMPO oxidation to the corresponding ot-aceto)y ketone in order to avoid racemisation of the monoacelylated intermediate. 

Microbial stereoinversion has been shown to be extremely flexible, as it is also applicable to sec-diols possessing two stereocenters (Scheme 2.132) [958-960]. Thus, meso- or rac-/rans-cyclohexane-l,2-diol was deracemized by... 

Introduction. (l/ ,5i -2//-l,5-Benzodithiepin-3(4/ -one 1,5-dioxide (C2-symmetric his-sulfoxide 1) has been used as a chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols via diastereoselective acetal cleavage reaction. The procedure consists of three steps (eq 1), that is, acetalization (step 1), acetal cleavage reaction followed by benzylation (step 2), and hydrolysis of the vinyl ether (step 3). Due to the Ca-symmetry of 1, the chiral auxiliary gives only one product in step 1. In addition, no regio- or geometric isomers of the enol ether are formed in step 2. This reagent can be recovered by acid-promoted hydrolysis and reused. 

If X is weakly nucleophihc (e.g., X = S04 or Cl04 ), the protonated oxirane is attacked by H2O and 1,2-diols are formed. For symmetrically substituted systems like ds-and trans-2,3-dimethyl oxirane or cyclohexene oxide, the acid-catalyzed hydrolysis follows a bimolecular SN2-hke mechanism, as indicated by its stereospecific outcome Products are rac-butane-2,3-diol, meso-butane-2,3-diol, and trans-cyclohexane-l,2-diol, respectively. 

Acetal Fission in Desymmetrization of 1,2-DioIs. The asymmetric desymmetrization of cyclic icso-l,2-diols was accomplished via diastereoselective acetal fission. After acetalization of meso-1,2-diols with the C2-symmetric bis-sulfoxide ketone, the resulting acetal was subjected to base-promoted acetal fission, followed by acetylation or benzylation to give the desymmetrized diol derivatives. Interestingly, the counter-cation of the base had a remarkable effect on the diastereoselectivity of the reaction. While LHMDS produce the desired compound with low diastereoselectivity, 90% and >96% diastereomeric excesses were obtained with NaHMDS and KHMDS, respectively. The best results were obtained using 3 equiv of KHMDS and 18-crown-6 in THF, which led to the formation of the desired acetate in 90% yield and 96% de (eq 50). ... 

The thermoset PCL-related bioelastomers from PCL diol M 530, 1250 and 2000 g mol ), tricarballylic acid and meso-l,2,3,4-butanetetracarboxylic acid were prepared by polycondensation as shown in Scheme 8.9. The prepolymers... 

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