Stereochemical purity, determination

Squaric acid 3-Cyclobutene-1,2-dione, 3,4-dihydroxy- (2892-51-5), 76, 190 Stannanes, chiral a-alkoxyallylic, 77, 103 Stereochemical purity, determination of, 76, 52... 

In conclusion, the most important result is that the use of permethylated cyclodextrin as chiral solvating agent for NMR spectroscopy not only affords a simple and practical way for the determination of the stereochemical purities of trisubstituted allenes, but also allows one to simultaneously determine their absolute configuration. Indeed, TRIMEB induced only positive complexation shifts of all the allene protons, which are greater for the (S )-enantiomer than for the (R)-enantiomer, independent of the structure of the allene. This empirical correlation seems to be reliable since it has been satisfied by a large number of trisubstituted allenes. 

Further process optimization by Thiruvengadam and co-workers (Thimvengadam et al., 1999), led to a novel, stereoselective, scalable two-step process devoid of chromatography for chiral 2-azetidinone construction (Scheme 13.4). As above, the titanium-enolate of chiral oxazolidinone 11a was preformed, but now when reacted with well behaved imines of type 16, affords the unexpected anti-addition product. This surprising result was further supported by careful comparison to minor antiproducts obtained in the earlier aldol-addition methodology and determination that the major product was indeed 17a (undesired RSR series). Adjustment of the oxazolidinone absolute stereochemistry to the fortuitously less expensive 2S-series afforded the desired diastereo-mer 17b in 95% de and in 50-70% yield. Recrystallization improved the stereochemical purity to >99% de. 

Bomane-10,2-sultam (362) and its antipode, accessible from inexpensive (+)- and (-)-camphorsulfonic acid in two simple operations, were introduced in 1984 and rank today among the most practical auxiliaries (Scheme 88). Both chirophore enantiomers are commercially available in kg quantities. Almost all of their A -acyl derivatives are stable and can be (1) readily purified by crystallization, (2) directly analyzed by H NMR and/or GC to determine their stereochemical purity, and (3) cleaved e.g. with UAIH4, LiOH, LiOOH, MeOMgl, etc.) under mild conditions without loss of the induced chirality and with excellent recovery of the auxiliary. 

Optical rotation has the dual advantages of historical use and widespread recognition in the compendia. For an enantiopure material, it defines its configuration when used in conjunction with other valid chemical tests. However, optical rotation has been used ineffectively when the primary analytical goal is the determination of stereochemical purity. The limits selected for the specification seem to be unrelated to the purity required by other methods. For example, the compendial monograph for naproxen requires that the drug substance meet a specification of "between -f-63.0 and -1-68.5"" in a chloroform solution. Based on the published specific rotation, this corresponds to a stereochemical purity of 95.5 to 103.7%, compared to the assay limits of 98.5 to 100,5%, determined by titration with sodium hydroxide (5). 

The stereochemical purity of the product is determined by reacting a sample of the product (15 mg) with 2,4-dinitrofluorobenzene (13 pL) in CH2CI2 (5 mL). The yellow solution is diluted with ethanol (1 10), then analyzed by HPLC on an N-naphthylleucine column (4.6 x 25 mm, Regis) eluted with IPA/hexanes (8 92) at 1 mL/min while monitoring at 350 nm. The retention times of the trans enantiomers are 17.4 and 19.1 min, while those of the cis enantiomers are 24.4 (1R,2S) and 27.1 (1S,2R) min. The product is enantio- and diastereomerically pure after recrystallization from toluene. 

As an outsider in the chemistry of bicyclic aliphatic hydrocarbons, I have the feeling that these reactions are intrinsically so complex that it is too difficult to deduce from them generally applicable rules for deamination mechanisms. It would appear that concentration on reagents as simple in structure as possible would be more promising, as purity determinations by instrumental analyses of all types are easier to interpret and as the number of products would be smaller. This is clearly indicated by some of the reactions discussed in Section 7.3, particularly Brosch and Kirmse s stereochemical investigation (1991) of the [l- H]butylamine deamination and the reactions investigated by Fishbein s group, namely the first steps of the methylamine nitrosation (Hovinen and Fishbein, 1992 Hovinen et al., 1992), the decomposition... 

Determination of the eudismic ratio is obviously dependent on the stereochemical purity of the material under examination. This is particularly... 

The dehydration of lactic acid to make the prepolymer should start with an —OH to —COOH ratio of 1 1. All other components with —OH and —COOH functionality disrupt the stoichiometric balance and may be incorporated as comonomers during prepolymerization, which limits the final lactide production yield from lactic acid. Little public information is available on the technical and economic relationship between lactic acid quality and lactide synthesis. Only a few patents mention the effect of metal impurities on racemization [68,69]. Stereochemical purity is one of the key parameters determining lactic acid purity. 

The choice between distillation, crystallization, or novel separation methods such as absorption or membrane separation is determined by the desired stereochemical purity of the product. Crystallization yields highly pure lactide, suitable, for example, for high-melting PLLA homopolymer of high molecular weight. Affordable distillation equipment does not fully remove all mc.yo-lactide, and consequently, a lactide monomer mixture for PLA copolymers with other thermal properties is obtained upon ring-opening polymerization. 

The enantiomeric purity of vinylsilane (S)-3a and (R)-3c are determined to be >95% ee by 1H-NMR (400 MHz) on the derived mandelate ester, obtained by a DCC-promoted coupling to (R)-O-acetylmandelic acid, and absolute stereochemical assignment is accomplished by 1H NMR analysis of the derived (R)-O-acetyl-mandelate esters. For details of this procedure see the published method of Trost.3... 

CSAs have found stereochemical applications in areas other than those of enantiomeric purity and absolute configuration determination. 

Organosulfur chemistry is presently a particularly dynamic subject area. The stereochemical aspects of this field are surveyed by M. Mikojajczyk and J. Drabowicz. in the fifth chapter, entitled Qural Organosulfur Compounds. The synthesis, resolution, and application of a wide range of chiral sulfur compounds are described as are the determination of absolute configuration and of enantiomeric purity of these substances. A discussion of the dynamic stereochemistry of chiral sulfur compounds including racemization processes follows. Finally, nucleophilic substitution on and reaction of such compounds with electrophiles, their use in asymmetric synthesis, and asymmetric induction in the transfer of chirality from sulfur to other centers is discussed in a chapter that should be of interest to chemists in several disciplines, in particular synthetic and natural product chemistry. 

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