Stereochemistry comparing configurations

Nucleophilic substitution reactions that occur under conditions of amine deamination often differ significantly in stereochemistry, compared with that seen in halide or arenesulfonate solvolysis. The results of four key substrates are summarized in Table 5.13. It can be seen (entry 1) that displacement of nitrogen on the 1-butyldiazonium ion is much less stereospecific than the 100% inversion observed on acetolysis of the corresponding brosylate. Similarly, the secondary system (entry 2) affords 2-butyl acetate with only 28% inversion of configuration. Furthermore, a crossover to net retention of configuration is observed as the alkyl group becomes better able to stabilize a carbonium ion. The small net retention (10%) observed in deamination of 1-phenylethylamine increases to 28% retention in the tertiary benzylic system 2-phenyl-2-butylamine. 

The 5-configuration of the fluoro alcohol has opposite stereochemistry compared to the 5-isomer of a-phenethanol. This is an artifact of Cahn-Ingold-Prelog priority rules. Cahn, R. S. Ingold, C. Pielog, V. Aneew. Chem. Int. Ed. Enel. 1966.5.385. 

Tetrahedral complexes arc also common, being formed more readily with cobali(II) than with the cation of any other truly transitional element (i.e. excluding Zn ). This is consistent with the CFSEs of the two stereochemistries (Table 26.6). Quantitative comparisons between the values given for CFSE(oct) and CFSE(let) are not possible because of course tbc crystal field splittings, Ao and A, differ. Nor is the CFSE by any means the most important factor in determining the stability of a complex. Nevertheless, where other factors are comparable, it can have a decisive effect and it is apparent that no configuration is more favourable than d to the adoption of a tetrahedral as opposed to... 

The desilylacetylated qrcloadducts, produced from the reactions of trimethylsilyl-diazomethane with 3-crotonoyl-2-oxazolidinone or 3-crotonoyl-4,4-dimethyl-2-oxa-zolidinone, were transformed to methyl traws-l-acetyl-4-methyl-l-pyrazoline-5-car-boxylate through the reactions with dimethoxymagnesium at -20 °C. When the optical rotations and chiral HPLC data were compared between these two esters, it was found that these two products had opposite absolute stereochemistry (Scheme 7.39). The absolute configuration was identified on the basis of the X-ray-determined structure of the major diastereomer of cycloadduct derived from the reaction of trimethylsilyldiazomethane to (S)-3-crotonoyl-4-methyl-2-oxazolidi-none. 

The stereochemistry of acyclic anionic oxy-Cope rearrangements is consistent with a chair TS having a conformation that favors equatorial placement of both alkyl and oxy substituents and minimizes the number of 1,3-diaxial interactions.214 For the reactions shown below, the double-bond configuration is correctly predicted on the basis of the most stable TS available in the first three reactions. In the fourth reaction, the TSs are of comparable energy and a 2 1 mixture of E- and Z-isomers is formed. 

On the other hand, optically active telluroxides have not been isolated until recently, although it has been surmised that they are key intermediates in asymmetric synthesis.3,4 In 1997, optically active telluroxides 3, stabilized by bulky substituents toward racemization, were isolated for the first time by liquid chromatography on optically active columns.13,14 The stereochemistry was determined by comparing their chiroptical properties with those of chiral selenoxides with known absolute configurations. The stability of the chiral telluroxides toward racemization was found to be lower than that of the corresponding selenoxides, and the racemization mechanism that involved formation of the achiral hydrate by reaction of water was also clarified. Telluroxides 4 and 5, which were thermodynamically stabilized by nitrogen-tellurium interactions, were also optically resolved and their absolute configurations and stability were studied (Scheme 2).12,14... 

The wavelength dependence of specific rotation and/or molecular ellipticity is called the Cotton effect. The Cotton effect can provide a wealth of information on relative or absolute configurations. The sign of the Cotton effect reflects the stereochemistry of the environment of the chromophore. By comparing the Cotton effect of a compound of known absolute configuration with that of a structurally similar compound, it is possible to deduce the absolute configuration or conformation of the latter. 

Dimethylnonyl propanoate 196 (Scheme 22), the female produced sex pheromone of several corn root worm species, Diabrotica spp. keeps ( -configuration at the methyl branching, whereas the stereochemistry at the oxygen function may vary with species (including the formation of mixtures) [359,360]. The structure of the pheromone of the southern corn root worm D. undecim-punctata, ( )-10-methyltridecan-2-one 197, is closely related to 196 [361,362]. Compared with 196 and 197, (6R, 122 )-6,10-dimethylpentadecan-2-one 198, the sex pheromone of D. balteata shows similar structural features [363,364]. 

The impressive increase in the ee values achieved in stoichiometric reactions compared to those in catalytic runs strongly indicates that the configuration at the metal correlates with the stereochemistry of the catalytic outcome only if (R, Rc)-9 and (Sj, Rc)-9 diverge in enantioselection, it is possible to achieve zero ee working with / jr,/ c/5ir,/ c mixtures and up to 93.5% ee using pure (Sir,Rc)-9 as catalyst. 

For convenience the imine is drawn here with a Z configuration, but in reality the favoured stereochemistry is thus, inversion of double bond geometry is necessary prior to ring closure. This requirement contributes to the relative severity o1 the conditions needed for cyclization compared to those needed (or the ring closure of the corresponding benzylamines. where there is free rotation about the C-N bond. 

In 1993, Evans and co-workers examined phe-box 6, /-pr-box 45, and bu-box 3 ligands in the Diels-Alder reaction of cyclopentadiene 68 and 3-acryloyl-l,3-oxazolidin-2-one 69 using a weak Lewis acid such as copper(II) triflate." The results are summarized in Table 9.9. The reaction was carried out between —50 and —78 °C for 3-18 h and achieved selectivities of up to 98 2 (endo/exo) with an endo ee of >98% (using bu-box 3). Interestingly, the enantiomer produced in these reactions was the (25) configuration, compared to the (2K) isomer obtained with iron(III) and magnesium(II) as reported by Corey. This observed stereochemistry was explained by the chelation model of the copper(II) complex 74 (Fig. 9.23)... 

When pyruvate with a chiral methyl group is carboxylated by pyruvate carboxylase the configuration at C-3 is retained. The carboxyl enters from the 2-si side, the same side from which the proton (marked H ) was removed to form the enolate anion (Eq. 14-12). Comparable stereochemistry has been established for other biotin-dependent enzymes.64 65... 

The relatively constant kinetic disadvantage experienced by an average vinylcyclopropane rearrangement, compared with a (kt + k2) stereomutation, amounts to a A A (7 of about 3 kcal moT1. This may well be associated with configurationally distinct sets of diradical structures with those of E stereochemistry favored thermodynamically over those of Z stereochemistry by about 3 kcal mol 1. Only the latter may lead to cyclopentene products212. 

The 3-(acetylsulfanyl)alkanoic acids 7 are obtained as a mixture of stereoisomers that are not separated in subsequent synthetic steps. In most cases, these sulfanylalkanoyl compounds are obtained as a mixture of four stereoisomers. The stereochemistry of one derivative [8, R1 = Bzl R2= iBu R3= Me) has been determined using HPLC and NMR data.1141 The ratio of the isomers is 3.5 3.5 1 1 for 8a/8b/8c/8d, respectively. This indicates that one set of enantiomers of the precursor 7, which is obtained by addition of thiolacetic acid to 6, is formed in a greater proportion than the other set of enantiomers. Therefore, it was concluded that isomers 8a and 8b are obtained from the major set of enantiomers of 7, while 8c and 8d are formed from the minor set of enantiomers. The NMR spectra of the separated isomers, 8a/8b/8c/8d, was compared to the spectrum of Phe-Ala. This allowed determination of the relative configuration of the benzyl group at the C5 asymmetric carbon of the 8 related to the adjacent Ala residue. The configuration at C5 of all four stereoisomers is shown in Scheme 2. The configuration at C6 has not been determined. 

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