Diastereoisomeric excess

Given a good diastereoisomeric excess in the initial formation of the /3-hydroxysilane, either geometrical isomer of the alkene can be obtained. 

Chiral heterocyclic compounds containing vicinal oxygen and nitrogen atoms were achieved by an asymmetric Diels-Alder reaction [111] of chiral acylnitroso dienophiles 111. The latter were prepared in situ from alcohols 110, both antipodes of which are available from camphor, and trapped with dienes (Scheme 2.46). Both the yield (65-94 %i) and diastereoisomeric excess (91-96%) were high. 

A number of (S)- or (R)-2-aminoamides were independently obtained by running reactions between chiral 2-bromoamides 1 and an achiral primary or secondary amine, in both sets of conditions (ref. 5). Accordingly, either a diastereoisomeric mixture or a single diastereoisomer in high diastereoisomeric excess, resulted respectively when an (S,R)- or (S)-2-bromoamide is treated with a chiral amine, again in the two sets of conditions. 

Water, which can be taken to a minimum by the use of molecular sieves, can produce a lactamide either through direct reaction with the aziridinone intermediate, or upon hydrolysis of oxazolidinone self-condensation products, previously obtained also in the presence of a strong non-nucleophilic base (H ) (ref. 17). The recently reported 0-self-alkylation compound H bears the (S,S)-configurations at the unreacted C-Br and newly formed C-0 bonds. The presence of bromine was expedient for the x-ray assessment of configuration at the two chiral centers of 11 which forms in high diastereoisomeric excess (ref. 5). 

More recently, in light of the development of the Sharpless asymmetric dihydroxylation protocol [20], we have approached the synthesis of diols such as 14 (Scheme 2) from the alkene. Thus, treatment of the alkenyl D-glucosides 15 vmder the conditions of the Sharpless dihydroxylation gave a range of diols 16 with varying diastereoisomeric excesses (Table 1). One of these mixtures of diols, upon recrystallization, yielded the pure diastereoisomer, namely the diol 14. This procedure now gives a very rapid and efficient entry into one of the precursor diols for the synthesis of the optically-pure epoxides [21]. 

Table 1. Diols 16 with varying diastereoisomeric excesses obtained by treating alkenyl D-glucosides 15...

With (2) and furan at 0°C a yield of 50% could be achieved with an exo-endo ratio close to 1 but a very high diastereoisomeric excess (>98 d.e.) for each adduct. The accompanying scheme shows how the endo adduct (4) led to the oxanorbornenone (5), a useful synthon in asymmetric synthesis of sugars. 

Diarylethene switches are present in two, rapidly exchanging conformations (P and M helicity), which upon photochemical ring-closure lead to the RR or SS enantiomers in equal amounts. The authors showed that aggregation of a chiral diarylethene switch in the open form 283 leads to selection of only one of the helical forms of 283 in the gel state. Subsequent photochemical ring-closure of 283 to 284 in the gel state proceeds with 96% diastereoisomeric excess and a photosta-tionary state (PSS) of 40%, whereas in solution, no stereoselection is observed. 

When the /i-amino acid moiety is inserted into a monocyclic or bicyclic structure such as 70 and therefore possesses chiral centers at both the a and / positions, high diastereoisomeric excesses are sometimes observed, as reported in Scheme 1.26 [75],... 

Inspired by this work, Mukaiyama et al. [22] used the silylated chiral alcohol 53 and performed the same reaction using diphenylboryltriflate as the catalyst. In all cases, the yields were good and the diastereoisomeric excesses excellent, except for benzaldehyde (Scheme 13.20, entry 5). 

The first examples of the diastereoselective aminohydroxylation of chiral acryl amides, R3CH=C(R2)CONHCH (Me)R1, have been reported. The reaction is believed to proceed within the so-called second catalytic cycle with diastereoisomeric excesses (g) reaching >99 1. The reaction relies solely on the stereochemical information provided by the enantiomerically pure starting materials. A stereochemical model for the observed asymmetric induction has been proposed.128... 

Stereoselective reactions are those that result in the selective production of one of the stereoisomers of the product. The extent of the selectivity may be recorded as the enantiomeric excess (e.e.) when the reaction produces a mixture of enantiomers and the diastereoisomeric excess (d.e.) when it produces a mixture of diastereoisomers. These quantities are defined by the expression ... 

The high-yield synthesis of the racemate via a Strecker synthesis is elegantly combined with the asymmetric transformation process. Addition of the resolving agent (S)-mandelic acid results in the formation of both diastereoisomeric salts. In the presence of benzaldehyde these salts are in equilibrium with the Schiff base, which racemizes readily. The low solubility of the diastereoisomeric salts (in apolar solvents) eventually allows obtainment of a >95% yield of the (/f) (.S )-salt in more than 99% diastereoisomeric excess. After decomposition of this salt by hydrochloric acid, pure (Ah-phenylglycine amide is obtained, and the resolving agent can be recycled. 

The asymmetric Strecker reaction of (f )-PGA (1), pivaldehyde (2), and HCN generated in situ21 from NaCN/AcOH in methanol as solvent gave the (R,S)-3 and (R,R)-3 aminonitriles in 80% yield. However, the diastereoisomeric excess was only 30%. It was found that by performing the reaction in water and heating for 24 hours at 70°C, the de of aminonitrile (R,S)-3 could be increased to >98%. The isolated yield was 93%. 

Table 2 Diastereoisomeric excesses for chiral racemic softballs as a function of different chiral enantiopure guests ...

The use of chiral phenylglyoxylate gave better results. The use of chiral alcohols gave diastereoisomeric excess in the range of 4-80% (Scheme 3.33) [66— 68]. The authors observed also an important variability of the diastereoisomeric excess in function of the temperature, with the presence of an inversion temperature. These results were explained assuming that the diastereoselection is produced on two levels (1) the preferred formation of the diastereoisomeric 1,4-biradical intermediate 34 and (2) the preferred retrocleavage of the energetically... 

The diastereoisomeric excess in the high-temperature region (T > Tinv) is dominantly controlled by steric effects of the chiral auxiliaries, whereas in the low-temperature region (T < Tinv), the nature of the olefin has a dominating influence. When the reaction is carried out on 2-methylfuran, a 2 1 regioisomeric... 

The best results can be obtained considering the energy of the triplet biradical intermediates (Fig. 3.19). Calculations on these biradical intermediates showed that the first (the precursor of the observed product) was more stable than the other by 0.73 kcal mol-1. Furthermore, the first and the second possible biradical intermediate in the reaction of the ester of (S)-2-methyl-l-butanol and differed by only 0.02 kcal mol-1, in agreement with the observed no stereoselectivity of the reaction. Finally, the first biradical intermediate in the reaction of 8-phenyl-menthol ester proved to be more stable than the other one by 21.9 kcal mol-1. This result is also in agreement with the observed high diastereoisomeric excess. 

Griesbeck and Mattay described photocycloaddition of methyl and ethyl trimethyl pyruvates (25) with di-isopropyl-1,3-dioxol. In contrast to the reaction with ethyl pyruvate, the bicyclic oxetane 26 was formed with very high (>98%) diastereoisomeric excess (Sch. 7) [29]. An X-ray analysis revealed the unusual endo-tert-butyl configuration. Semiempirical calculation indicated that this clearly is the kinetic product formed by a biradical... 

The major adduct exo(c)-195 was isolated by crystallization from the reaction mixture (33% yield) and its stereochemistry was unequivocally established as exo with respect to the sulfinyl group by X-ray diffraction studies. The other three adducts could not be separated, but traces of one of them could be identified as a regioisomer of compound 195. From this fact and consideration made on the H NMR spectra obtained from the reaction mixture, the authors conclude that this reaction takes place with a high diastereoisomeric excess, the exo adducts being favored. This stereochemical course was explained by assuming that the approach of the 1,3-dipole takes place from the face supporting the lone... 

Optical purity is defined by the terms enantiomeric excess(tt) and diastereoisomeric excess de) given by the formula shown below. 

The reaction of the silyloxypyrroles 47 possessing a chiral substituent at the nitrogen atom, with cyclobutanone in the presence of a Lewis acid, followed by an acid induced ring expansion of the cyclobutanol intermediate 48, offers an asymmetric route to the l-azaspiro[4.4]nonanes 49 in good diastereoisomeric excess <02SL1629>. In this context it might also be interesting to... 

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