Diastereomer ratio

The effect of the counterion on the diastereomer ratio was investigated in detail for the Peterson condensation3 of phenyl(trimethylsilyl)methanide with benzaldehyde2 or substituted cyclohexanones4 and was found to be remarkably low. The variation of the solvent and the temperature has an influence of similar magnitude. 

Based on capillary GC analysis of the purified carbamates 12. Entries 2-6 The diastereomer ratios are minimal values calculated by comparison to the next largest peak in the GC. 

The benzylcarbamates are formed in higher yields (entry 8 83 %. entry 9 75%) with similar diastereomer ratios. 

The diastereomer ratio is determined by analysis of the Ml-NMR spectrum of the crude product if possible. 

Conjugate Addition. To a solution of 1.5 mmol of lithium dialkylcuprate at — 25 CC is added 1 mmol of methyl ( )-3-[(25,45,55)-3-benzyloxycarbonyl-4-methyl-5-phenyl-2-oxazolidinyl]-propenoate dissolved in 1 mL of dry diethyl ether. After 30 ntin at — 25 C, the mixture is treated with an aq NH3/NH4C1 pH 8 buffer solution and then stirred at r.t. for 15 min. After diethyl ether extraction, the organic layers are dried over Na,S()4 and filtered and the solvent is evaporated under reduced pressure. The crude products are checked by H- and l3C-NMR analyses in order to determine the diastereomer ratios (g 95 5) and then purified by flash chromatography (hexane/ethyl acetate 80 20) yield 70-72%. 

The reaction simply proceeds with retention of configuration, and the diastereomer ratio reflects that of the alkylation. 

Prior literature indicated that olefins substituted with chiral sulfoxides could indeed be reduced by hydride or hydrogen with modest stereoselectivity, as summarized in Scheme 5.10. Ogura et al. reported that borane reduction of the unsaturated sulfoxide 42 gave product 43 in 87 13 diastereomer ratio and D20 quench of the borane reduction mixture gave the product 43 deuterated at the a-position to the sulfoxide, consistent with the hydroboration mechanism [10a]. In another paper, Price et al. reported diastereoselective hydrogenation of gem-disubstituted olefin rac-44 to 45 with excellent diastereoselectivity using a rhodium catalyst [10b],... 

Boehm et al.100 have synthesised and studied a series of half-sandwich rhodium (III) and iridium (III) complexes, derivatives of salicylaldehyde and L-amino acid esters. The diastereoselectivity has shown strong dependence on the type of metal as well as amino acid residue. The labile configuration of the metal atoms was suggested because of changes in the diastereomers ratio with increasing temperature. Fast epimerisation at the metal atom was suggested for some S-phenylalanine complexes. 

The Diels-Alder addition of PTAD to 607 in dichloromethane at room temperature is immediate and a mixture of diastereomers 608 and 609 is formed. The diastereomer ratio 92 8 obtained at room temperature is further improved to 97 3 when the reactants are mixed at — 78 °C and then warmed up to room temperature (Equation 91) <2004TL1519>. 

Among heteroaromatic compounds able to react with nitrile oxides as dipo-larophiles, furan, probably, is the best known. Recently, a novel nitrile oxide was generated from a sulfoximine and converted in situ to a cycloadduct with furan (Scheme 1.25) (287). The starting racemic N-methyl-S-nitromethyl-S-phenylsul-foximine 124 was prepared in 87% yield via nitration of N,S-dimethyl-S-phenyl-sulfoximine. Reaction of 124 with p-chlorophenyl isocyanate and a catalytic quantity of triethylamine, in the presence of furan, afforded dihydrofuroisoxazole 125, the product of nitrile oxide cycloaddition, in 42% yield (65 35 diastereomer ratio). The reaction of 125 with phenyllithium and methyllithium afforded compounds 126, which are products formed by replacement of the sulfoximine group by Ph and Me, respectively. 

Second, the diastereomers ratio in C,C-coupling products of cation (349) with silyl ketene acetal exactly corresponds to the conformers ratio for this cation (349a 349a ), that is, it is evident that the interaction occurs through the distal approach of silyl ketene acetal to the C-6 atom of observed conformations a and a of the above mentioned cation. 

Fig. 31.4 Solvate dihydrides characterized at low temperature [S = CH3OH or CD3OD]. Dihydrides formed in situ react rapidly with the common substrates of enantioselective hydrogenation, and the reduced product is formed with high enantios-electivity. At ambient pressure, the proportion of dihydrides is 45% at -100°C for (a) with a 10 1 diastereomer ratio, and 40% for (b) at —40°C, with a 2 1 diastereomer ratio.

Reduction of diketones such as pentane-2,4-dione using (RfBiNAP-RuCF under hydrogen (75 100 atm) gives the corresponding diol, in this case (R),(R)-2,4-pentanediol with an excellent diastereomer ratio (98 %) and optical purity (>99 %)[48]. 

By quenching the aminolysis reaction at various times and examining the diastereomer ratios in the unreacted Co(III)-ester and Co(III)-dipeptide products it has been possible to build up complete concentration-stereochemistry-time profiles for several couplings. One such example is given in Fig. 7, and kinetic analysis of these data allows the rate constants for epimerization (ku k2) and aminolysis (k3, ki) to be found. Some results obtained in this way are listed in Table X. 

Diastereomer Ratios" in the Formation of Tetrahydro-1,3-oxazin-4-ones 133 and 134... 

For the diastereomer ratios see text. In all cases, only two diastereomers were isolated. - Reaction was performed in THF/CH2CI2 mixture. 

It is noteworthy that the substituent at C-2 appears to be very important for the diastereoselectivity at C-2. The unsubstituted methyl 2-chloro-2-cyclopro-pylideneacetate 1-Me and the spirocyclopropanated analogs 2c-Me, 2c-Bn add the oxazolidinone 100 to form 102a-Me, 102c-Me and 102c-Bn only with moderate selectivities (diastereomer ratios were 3 1, 42 11 34 13 and 27 59 14, respectively) [10b,21]. 

Greene and coworkers showed that deprotonation of Af-Boc-iV-benzylamine with a threefold excess of s-BuLi and twofold excess of TMEDA yields a dilithiated species which adds in a 1,2-fashion to acrolein in 49% yield. The syn anti diastereomer ratio is 86 14 (Scheme 49). The racemic mixture of diastereomers can be protected, oxidized and resolved to yield the enantiomerically pure (>99%) acid shown in 46% overall yield. This molecule is a precursor to the side chain of Taxol. ... 

The mechanism of this sequence is enlightening when contrasted with the mechanism of the formamidine auxiliary (Scheme 56). Scheme 59a illustrates the results of some deprotonation-alkylation experiments on deuteriated diastereomers. ° ° Two features of the product of these experiments were examined the diastereomer ratio and the percent deuterium incorporation. The deuterium incorporation in the product reveals that there is a preference for removal of the -proton. When deuterium is in the -position, this selectivity is opposed by the isotope effect, and the product has about half the original deuterium remaining. When deuterium is in the a-position, the selectivity for the -proton (imposed by the chiral auxiliary) and the isotope effect act in concert, and virtually all the... 

Our preliminary experiments have provided the first example of Lewis acid promoted C-C bond heterolysis of epoxides and productive cycloaddition (eq 7). Under the influence of TiCl4-(THF)2 (2 equiv), epoxide 26 reacts with methyl pyruvate to provide acetal 27 (52% isolated yield), along with C-O cleavage product 28 (23 °C, 3 h). The diaste-reoselectivity for formation of 27 is 2.3 1. We have performed the analogous reaction in the absence of a Lewis acid the thermal reaction requires several days at 110 °C and gives a diastereomer ratio (dr) of ca. 1.3 1... Although not optimized from the standpoint of chemoselectivity, these results are promising because of the relatively low reaction temperature and potential for enhanced diastereocontrol. 

Diastereomer ratios were determined by gas chromatography. Since the aldol adduct undergoes retroaldol reaction on the column, it must be silylated prior to injection. Approximately 5 mg of the crude adduct is filtered through a short plug of silica gel to remove any trace metals. The material is taken up into 1-2 mL of dichloromethane in a 2-raL flask or small test tube. To this solution are added 4-5 drops of N,N-diethyl-1,1,1-trimethylsilylamine and a small crystal of 4-(N,N-dimethylamino)pyridine (Note 11), The solution is stirred for 2 hr and injected directly onto the column. (Column conditions 30 m x 0.32 mm fused silica column coated with OB 5, 14 psi hydrogen carrier gas, oven temperature 235°C). 

The applied catalytic system consisted of a Ru-Noyori-type racemization catalyst 1 (Fig. 12b) and Novozym 435. This catalyst combination tolerates a wide range of acyl donors, and it was expected that it would allow the use of bifunctional acyl donors for the formation of polycondensates. Before the start of the reaction, the monomer mixture showed the expected diastereomer ratio of (S,S) R,R) R,S) of 1 1 2 of the 1,4-diol employed. After 30 h of reaction the (5,5)-enantiomer almost completely disappeared, whereas the ratio of [R,R)- to (/ , 5)-monomer was ca. 3 1 (R S ca. 7 1). At a hydroxyl group conversion of 92% after 70h, no further conversion was observed and a final ratio of R,R) to R,S) of 16 1 (R S ca. 33 1) was obtained. Unfortunately, the molecular weights of the polymer were moderate at best (Mw = 3.4kDa) and Novozym 435 had to be added every few hours to compensate for the activity loss of the lipase. This suggests that Ru-catalyst 1 and Novozym 435 are not fully compatible. 

Some additional examples, where the stereochemical outcome of the cycloaddition to chiral alkenes has been explained in terms of the Honk—Jager model, should also be mentioned. The diastereomer ratio found in the reaction of y-oxy-a,p-unsamrated sulfones (166), with Morita-Baylis-Hillman adducts [i.e., ot-(a -hydro-xyalkyl)-acrylates (167)] (Scheme 6.27), with dispiroketal-protected 3-butene-l,2-diol (168), and with a,p-unsamrated carbonyl sugar and sugar nitroolefin (169) derivatives, all agree well with this model. 

The use of chiral auxiliaries to induce (or even control) diastereoselectivity in the cycloaddition of nitrile oxides with achiral alkenes to give 5-substituted isoxazolines has been investigated by a number of groups. With chiral acrylates, this led mostly to low or modest diastereoselectivity, which was explained in terms of the conformational flexibility of the vinyl-CO linkage of the ester (Scheme 6.33) (179). In cycloadditions to chiral acrylates (or acrylamides), both the direction of the facial attack of the dipole as well as the conformational preference of the rotamers need to be controlled in order to achieve high diastereoselection. Although the attack from one sector of space may well be directed or hindered by the chiral auxiliary, a low diastereomer ratio would result due to competing attack to the respective 7i-faces of both the s-cis and s-trans rotamers of the acrylate or amide. 

The reactions generally produce a 1 1 mixture of diastereomeric isoxazoline adducts (Table 6.10), except for a few cases with diastereoselectivity of 70 30 (221). A selection of results concerning diastereomer ratios and yields is gathered in Table 6.10. 

Yamamoto and co-workers (135,135-137) recently reported a new method for stereocontrol in nitrile oxide cycloadditions. Metal ion-catalyzed diastereoselective asymmetric reactions using chiral electron-deficient dipolarophiles have remained unreported except for reactions using a-methylene-p-hydroxy esters, which were described in Section 11.2.2.6. Although synthetically very useful and, hence, attractive as an entry to the asymmetric synthesis of 2-isoxazohnes, the application of Lewis acid catalysis to nitrile oxide cycloadditions with 4-chiral 3-(2-aIkenoyl)-2-oxazolidinones has been unsuccessful, even when > 1 equiv of Lewis acids are employed. However, as shown in the Scheme 11.37, diastereoselectivities in favor of the ffc-cycloadducts are improved (diastereomer ratio = 96 4) when the reactions are performed in dichloromethane in the presence of 1 equiv of MgBr2 at higher than normal concentrations (0.25 vs 0.083 M) (140). The Lewis acid... 

Diastereomeric Excess (de) - This measure for characterization of mixtures of diastereomers should not be used. This volume uses the diastereomer ratio (d.r.) normalized to 100 whenever possible (see Section 1.2.2.2.). 

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