Enantiomerization pathways

Propellers of the type A13ZX may be analyzed in an analogous manner.9) The four classes of rotational mechanisms are retained, and an additional non-rotational pathway is added inversion at Z along the Z—X bond. Such inversion changes the configuration only with respect to the center of chirality, and has no effect on the other elements of isomerism. Enantiomerization pathways for an AraZX molecule of type 3 thus must include an odd number of inversions. 

The enantiomerization of 6,7-dihydro-dibenzo[///][l,2]diazocine-5,8-dione 2 was investigated using quantum-mechanical methods. At the density functional theory (DFT) B3LYP/6-31G(d,p) level, two enantiomeric -symmetric transition states (TSs) and two enantiomeric pathways were found with a calculated barrier of 155.6 kj mol-1. The pathways can be divided into two steps one involving primarily inversion of the amidic bridge and the other movement of the aromatic rings <2004TA537>. 

Returning to the evaluation of stereoisomers for candidates as ultimate phosphoranes, the isomer number is further reduced from four to two in each sector since ring strain effectively prevents access to the star-points (eering). Accordingly, the ultimate phosphoranes derived from cis-18 via 15 and 25 are identified as 24 and 14, respectively, for retention and 14 and 24, respectively, for inversion. The ultimate phosphoranes are the same, but the stereochemistry of displacement is reversed, when one starts from trans 18 via 25 and 15. Since enantiomers are indistinguishable under achiral conditions, further discussion need only consider one of the two enantiomeric pathways, e.g., the pathway on the top of the hexagon. 

Warshel and Shakked have calculated (56) the energies of exclmer formation for the two enantiomeric pathways In the phenyl compound. Because of the nonplanarlty of the molecule and the nonequallty of enantiomeric Intermolecular contacts In the chiral crystal, these energies are not equal this difference Is felt particularly for small displacements along the reaction coordinate, and one may well expect that the effect will be amplified by relaxation of the environment. Thus this approach may Indeed give an acceptable Interpretation of the source of the asymmetric Induction. 

Only reaction 1 provides a direct pathway to this chiral molecule the intermediate 2-methyl-butanal may be silylated and reacted with formaldehyde in the presence of the boronated tartaric ester described on page 61. The enantiomeric excess may, however, be low. 

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

Similar methodology has been applied in the syntheses of 2-amino-3-hydroxycarboxylic acids in high diastereomeric and enantiomeric purity. Two separate pathways give either the antt- or. WM-products. The first strategy relies on haloacetate precursors derived either from (S )-valine 17"- oi or from norephedrine 18102, which are converted into the boron enolates103 and subsequently reacted with aldehydes to deliver. ym-adducts99 102. The diastereomeric ratio, defined as the ratio of the desired diastereomer/the sum of all others, is 50 1 for the former and about 95 5 for the latter adducts. 

The reactions of trans- and m-Co(en)2Cl7 (recall that the cis isomer can be resolved into an enantiomeric pair) can be considered.18 The question is whether a common intermediate prevails along the pathway for the reaction in which a single Cl is lost ... 

An enantioconvergent transformation leads to a single enantiomeric product from a racemate [51]. Each enantiomer is transformed via independent pathways by the same catalyst or by two different catalysts (Figure 6.6). For example, the hydrolysis of epoxides may proceed with high regio- and stereoselectivity vdth inversion or retention of configuration. Several enantioconvergent transformations of epoxides are reported in the last section of this chapter. 

The catalytic enantioselective desymmetrization of meso compounds is a powerful tool for the construction of enantiomerically enriched functionalized products." Meso cyclic allylic diol derivatives are challenging substrates for the asymmetric allylic substitution reaction owing to the potential competition of several reaction pathways. In particular, S 2 and 5n2 substitutions can occur, and both with either retention or inversion of the stereochemistry. In the... 

With a common intermediate from the Medicinal Chemistry synthesis now in hand in enantiomerically upgraded form, optimization of the conversion to the amine was addressed, with particular emphasis on safety evaluation of the azide displacement step (Scheme 9.7). Hence, alcohol 6 was reacted with methanesul-fonyl chloride in the presence of triethylamine to afford a 95% yield of the desired mesylate as an oil. Displacement of the mesylate using sodium azide in DMF afforded azide 7 in around 85% assay yield. However, a major by-product of the reaction was found to be alkene 17, formed from an elimination pathway with concomitant formation of the hazardous hydrazoic acid. To evaluate this potential safety hazard for process scale-up, online FTIR was used to monitor the presence of hydrazoic acid in the head-space, confirming that this was indeed formed during the reaction [7]. It was also observed that the amount of hydrazoic acid in the headspace could be completely suppressed by the addition of an organic base such as diisopropylethylamine to the reaction, with the use of inorganic bases such as... 

Kinetic resolution can also be accomplished via eliminative pathways. Thus, the enantiomerically enriched allylic alcohol 102 can be prepared from the meso epoxide 96 with up to 96% ee by the action of LDA in the presence of the chiral diamine 101 and 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU). The DBU is believed to function as an aggregation modifier, and the active catalyst is theorized to be a heterodimer of the lithium amide (deprotonated 101) and DBU, although some nonlinear effects have been observed at low DBU concentrations <00JA6610>. Dipyrrolidino derivatives (e.g., 104) have also demonstrated utility with regard to kinetic resolution <00H1029>. 

The mechanism of the stereoselective syntheses of (K)-3-aryl-5-(hydroxy-methyl)oxazolidinones via the Mannenin reaction of aryl carbamic acid esters with (Jt)-glycidyl butyrate has been explored in detail by Brickner et al. [60]. Namely, N-lithiated carbamate derivatives of anilines are allowed to react with the commercially available (K)-glycidyl butyrate (96-98% enantiomeric excess ee) under appropriate conditions to obtain enantiomerically pure (Jt)-3-aryl-5-(hydroxymethyl)oxazolidinones in 85-99% yields, according the pathways depicted in Scheme 19. 

Qin S, Gan J (2006) Enantiomeric differences in permethrin degradation pathways in soil and sediment. J Agric Food Chem 54 9145-9151... 

Zirconocene-catalyzed kinetic resolution of dihydrofurans is also possible, as illustrated in Scheme 6.8 [18]. Unlike their six-membered ring counterparts, both of the heterocycle enantiomers react readily, albeit through distinctly different reaction pathways, to afford — with high diastereomeric and enantiomeric purities — constitutional isomers that are readily separable (the first example of parallel kinetic resolution involving an organome-tallic agent). A plausible reason for the difference in the reactivity pattern of pyrans and furans is that, in the latter class of compounds, both olefmic carbons are adjacent to a C—O bond C—Zr bond formation can take place at either end of the C—C 7T-system. The furan substrate and the (ebthi)Zr-alkene complex (R)-3 interact such that unfavorable... 

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