Phosphates chiral 1,3-diols

Toluene (300 mL) was added to (i-PrO)2TiCl2 (1.40 g. 5.9 mmol), the chiral diol (above equation, 3.12 g, 5.9 mmol) and 4 A molecular sieves (powder, 3.0 g) at 0 C and the mixture stirred for 30 min. The acrylamide 43 (R = Me 10.0 g, 71 mmol) in petroleum ether (200 mL) was added. Subsequently, a petroleum ether soln (100 mL) of ketene dimethyl thioacetal (44 10.0 g, 83 mmol) was added and the mixture stirred at 0 C for 1 h. The reaction was quenched by adding pi I 7 phosphate buffer and inorganic materials removed by filtration. The organic materials were extracted with EtOAc and the extracts washed with brine and dried (Na,S04). After evaporation of the solvent, the crude product was purified by eolumn chromatography yield 14.8 g (80%). Optically pure 45 was obtained by two recrystallizations from benzene/hexane (80% recovery) mp 90.5 92.0 C. 

Chirality transfer in catalytic asymmetric hydrogenation can be achieved not only by using powerful chiral ligands such as BINAP or DuPhos but also by the formation of a dynamic conformational isomer. The availability of many enantiomerically pure diols allows the production of electron-deficient, bi-dentate phosphate in the form of 27. The backbone O-R -O can define the chirality of the 0-R2-0 in complex 28, hence realizing the chirality transfer.44... 

Considerable ingenuity was required in both the synthesis of these chiral compounds695 697 and the stereochemical analysis of the products formed from them by enzymes.698 700 In one experiment the phospho group was transferred from chiral phenyl phosphate to a diol acceptor using E. coli alkaline phosphatase as a catalyst (Eq. 12-36). In this reaction transfer of the phospho group occurred without inversion. The chirality of the product was determined as follows. It was cyclized by a nonenzymatic in-line displacement to give equimolar ratios of three isomeric cyclic diesters. These were methylated with diazomethane to a mixture of three pairs of diastereoisomers triesters. These dia-stereoisomers were separated and the chirality was determined by a sophisticated mass spectrometric analysis.692 A simpler analysis employs 31P NMR spectroscopy and is illustrated in Fig. 12-22. Since alkaline phosphatase is relatively nonspecific, most phosphate esters produced by the action of phosphotransferases can have their phospho groups transferred without inversion to 1,2-propanediol and the chirality can be determined by this method. 

Kano has studied extensively the recognition of anions and zwitterions by both native and derivatized cyclodextrins [ 16]. The native (3-cyclodextrin com-plexation properties were examined with respect to binaphthyl derivatives. For both l,T-binaphthalene-2,2,-dicarboxylic acid and l,T-binaphthalene-2,2 -diol phosphate almost no chiral recognition was observed. The enantiomers of binaphthyl-2,2 -dicarboxylic acid were better distinguished using a per-O-methylated (3-cyclodextrin derivative in place of the native (3-cyclodextrin. 

Preparative Methods racemic l,l -bi-2,2 -naphthol (BINOL) is most conveniently prepared by the oxidative coupling reaction of 2-naphthol in the presence of transition metal complexes (eq 1). The resolution of racemic BINOL with cinchonine may be performed via the cyclic phosphate (eq 2). An alternative procedure to provide directly optically active BINOL is the oxidative coupling of 2-naphthol catalyzed by Cu salt in the presence of chiral amines (eq 3). The best procedure uses (+)-amphetamine as the chiral ligand and provides BINOL in 98% yield and 96% ee. Above 25 °C the Cu /(+)-amphetamine/(5)-BINOL complex precipitates, while the more soluble Cu /(+)-amphetamine/(I )-BINOL complex is slowly transformed into the former complex. 9,9 -Biphenanthrene-10,10 -diol has also been prepared in 86% yield and with 98% ee by a similar asymmetric oxidative coupling of 9-phenanthrol in the presence of (I )- 1,2-diphenylethylamine. ... 

The first example of the asymmetric synthesis of P-chiral trialkyl phosphates (12) via trialkyl phosphite, in which the keystone is dynamic kinetic resolution in the condensation of a dialkyl phosphorochloridite (13) and an alcohol by the catalytic assistance of a chiral amine has been reported (Figure 2)." 2,4-Dinitrophenol (DNP) was employed as an activating reagent with ben-zyloxy-bis-(diisopropylamino) phosphite to synthesize the cyclic phosphate derivatives (14) from a series of alkane diols HO-(CH2)n-OH (n=2-6). Included was a cyclic phosphate derivative of carbohydrate (15). The mechanism of activation by 2,4-DNP and cyclization was also described (Figure 3). ... 

To explore the viability of chiral auxiliaries in the vinyl phosphate-p-ketophosphonate rearrangement, a series of vinyl phosphates derived from ephedrine, pseudoephedrine, (lR,2S,5R)-(-)-menthol, (15,25,35,57 )-(-i-)-isopinocampheol, (5)-(-)-2-methylbutanol, binaphtol, and (2R,4R)- or (25,45)-pentane-2,4-diol have been examined. (5)-(-)-2-methylbutanol and 2,4-pentane-2,4-diol derivatives appear as the most attractive chiral auxiliaries. 

Scheme 39 shows the procedures of chemical derivatization of the chiral phosphomonoesters analyzed by the 31P NMR method. The procedures for phosphopropane-1,2-diol (55), 5 -AMP (67), 5 -dAMP (70), 3 -TMP (73), and glucose-6-phosphate (76) all involve a cyclization step (with inversion of configuration at phosphorus), followed by methylation or ethylation. The dipal-mitoylphosphatidic acid (79) was first converted to dipalmitoylphosphatidyl-ethanolamine (135), which was then silylated and analyzed by 31P NMR (136). 

Hennecke developed enantioselective haloetherification reactions via desymmetrisation of in situ generated meso-iodonium intermediates (Scheme 2.37). Chiral sodium phosphate 58 was used for the cyclisation of symmetrical ene-diol substrates 59 with l-iodopyrrolidin-2-one (60), and the corresponding iodoetherification products 61 were obtained with up to 71% ee. 

Scheme 2.37 Enantioselective haloetherification of ene-diols with the use of chiral sodium(i) phosphate.

Biocatalytic formation of chiral furane-diols via route A. 40 mL phosphate buffer 50 mmol L-1, pH 8.0, 5% v/v 2-MeTHF, 1.6 mmol furaldehyde, 4.8 mmol formaldehyde, 2.5mmol L-1 MgS04, 0.15 mmol L-1 ThDP, 168 U BAL, 1500 U GDH, 95 U FDH, NADH/NAD+1 mmol L-1 each... 

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