Enantiofacial selection

Catalytic asymmetric hydrogenation was one of the first enantioselective synthetic methods used industrially (82). 2,2 -Bis(diarylphosphino)-l,l -binaphthyl (BINAP) is a chiral ligand which possesses a Cg plane of symmetry (Fig. 9). Steric interactions prevent interconversion of the (R)- and (3)-BINAP. Coordination of BINAP with a transition metal such as mthenium or rhodium produces a chiral hydrogenation catalyst capable of inducing a high degree of enantiofacial selectivity (83). Naproxen (41) is produced in 97% ee by... 

With C2-symmetric reagents (5,5)-2,5-dimethyl-l-trifluoromethylsulfonylborolane34 and (R,R)-l-chloro-2,5-diphenylborolane , (S)-(3-ethylpent-3-yl) thiopropanoate is added, via the corresponding enolates, to aldehydes with remarkable auxiliary-induced stereoselectivity. Thus, /1-hydroxy thioestcrs arc obtained with 87-94% ee when the borolanyl triflate auxiliary reagent is used. These ee values do not exactly reflect the enantiofacial selectivity since the borolane is not available in enantiomerically pure form (see Section 1.3.4.2.2.2.). Use of the chiral chloroborolane auxiliary gives the thioestcrs with 95-96% cc70,11. o... 

It was found, furthermore, that the substituent on the sulfonamide group of the chiral hgand strongly influenced the enantiofacial selectivity. Hence, ligand 81 bearing a tosyl substituent delivered the endo-(2il)-cycloadduct, whereas a trifluoromethanesulfonamide group afforded its enantiomer. The authors proposed that the latter substituent should increase the Lewis acid-... 

Figure 3.3 Rationale for predicting the enantiofacial selectivity in Sharpless s dihydroxylation.

Desimoni et al. have shown that the use of magnesium perchlorate or magnesium triflate, and three chiral to(oxazolines) and two equivalents of achiral auxiliary ligands such as water or tetramethylurea, induces a strong change of the enantiofacial selectivity with >94% ee in the... 

Ethyl 2-phenylcyclopropanecarboxylate, obtained in the presence of 207a, has S configuration at C-l in both the cis- and trans-isomer. As that carbon has been furnished by the diazo ester, this result indicates enantiofacial selection at the carbenoid. In contrast, hardly any discrimination between the enantiofaces of the prochiral olefin occurs. Only when the ester substitutents become bulkier, does this additional stereochemical feature gain importance, and the S configuration at C-2 of the cyclopropane is favored. 

The high level of enantiofacial selection is made in the hydride transfer step 7C -> 7D [2], The chelating geometry in the transition state 7F decreases the activation energy. The chiral environment derived from (R)-BINAP clearly differentiates diastereomeric Si-7F and Re-7F (Fig. 32.7b). The Si structure affording the R alcohol is much more favored than the Re structure, which suffers from the Ph/R repulsion. 

Their interactions with the more hindered side of an asymmetrical olefin determine the orientation of the substrate during its approach to the metal-oxo bond and the subsequent enantiofacial selective oxygen transfer. 

As pointed out by Hosoya et al.92 the enantiofacial selection of ra-olefins is mainly controlled by the asymmetric centers at the C-8(8 ) carbons, while that of trans-olefins is preferentially controlled by the asymmetric centers at the C-9(9 ) carbons in 119 or 120. Optically active Mn(III)-salen complexes have catalyzed the epoxidation of m-olelins with higher ee (>90%), especially when they are conjugated with an acetylene or phenyl group. However, the epoxidation of trans-olefins with these salen complexes shows rather poor enantio-selectivity (Table 4-18). 

These recent results illustrate for the first time that metallocene-based chiral Lewis acids can serve effectively in providing [4+2] cycloaddition products with excellent levels of enantiofacial selectivity. Perhaps more importantly, the reported NMR studies and the observed dramatic solvent effect should pave the way for future endeavors in the rational design of better chiral metallocenes. 

Scheme 6.39. Variations in enantiofacial selectivity in reactions catalyzed by (ebthi)Zrbinol/MAO.

Efforts have been made to apply r 3-allyltitanium chemistry to the asymmetric synthesis of homoallylic alcohols and carboxylic acids. The synthesis and reactions of chiral r 3 -allyl-titanocenes with planar chirality, or containing Cp ligands with chiral substituents, have been reported [6c,15,30—32]. The enantiofacial selectivity in the allyltitanation reactions has been examined for the complexes 12 [15], 13 [30], 14 [31], 15, 16, and 17 [32] depicted in Figure 13.2. 

Asymmetric osmylation of alkenes.3 In the presence of 1 equiv. each of 1 and 0s04, alkenes undergo highly enantioselective ris-dihydroxylation. Highest enantiofacial selectivity (90-99%) is shown in osmylation of trans-di- and trisub-... 

In fact, the usefulness of chiral oxazoline enolates in asymmetric synthesis had been already demonstrated by Meyers [24]. Evans obtained enantiofacial selectivities (or enantiomeric excesses = e.e) equal to or greater than 99% (Table 9.4). 

Enantiofacial selectivity in the epoxidation of prochiral allylic alcohols (allylic alcohol drawn as it is shown OH down at the right side)... 

The presence of the stereogenic centre at C(l) introduces an additional factor in the asymmetric epoxidation now, besides the enantiofacial selectivity, the diastereoselectivity must also be considered, and it is helpful to examine epoxidation of each enantiomer of the allylic alcohol separately. As shown in Fig. 10.2, epoxidation of an enantiomer proceeds normally (fast) and produces an erythro epoxy alcohol. Epoxidation of the other enantiomer proceeds at a reduced rate (slow) because the steric effects between the C(l) substituent and the catalyst. The rates of epoxidation are sufficiently significative to achieve the kinetic resolution and either the epoxy alcohol or the recovered allylic alcohol can be obtained with high enantiomeric purity [9]. 

TScc is also the stage at which the enantiofacial selectivity of the reaction is determined [80]. This conflicts with the conventional assumption that the face selectivity is established in the initial Ti-complexation [40a], which is now shown to represent a preequilibrium state preceding TScc. The calculated activation energy taking the solvation of the lithium atoms into account shows reasonable agreement with recently determined experimental data [75]. 

The sense of the enantiofacial selection was predictable from the model complex of organolithium, imine and chiral diether 28, where the migrating C—Li bond is parallel to the 7T-system of the a,/3-unsaturated imine (Figure 4). From the favored complex the R group of the organolithium reagent is transferred to the less hindered face of the double bond of the unsaturated imine. 

Originally, it was proposed that lone pair repulsions between one of the tartrate ester carbonyl oxygens and the aldehyde oxygen in transition structure 60 were responsible for the preference for transition structure 59 and the consequent enantiofacial selectivity (Scheme 5). Recent theoretical calculations. 

The nonconventional tartrate esters 1-3 have been used to probe the mechanism of the asymmetric epoxidation process [20a]. These chain-linked bistartrates when complexed with 2 equiv. of Ti(0-f-Bu)4 catalyze asymmetric epoxidation with good enantiofacial selectivity. 

The scope of allylic alcohol stmctures that are subject to asymmetric epoxidation was foreshadowed in the first report of this reaction. Examples of nearly all the possible substitution patterns were shown to be epoxidized in good yield and with high enantiofacial selectivity [2], The numerous results that have appeared since the initial report have confirmed and extended the scope of the stmctures that have been epoxidized. This section of the chapter illustrates the structural scope without being exhaustive in coverage of the literature. Examples were chosen... 

Before commencing, the attention of the reader is drawn to the terms enantiofacial selectivity and diastereoselectivity. The usage in this chapter does not conform to the strictest possible definitions of these terms. In particular, enantiofacial selectivity is used with reference to the selection and delivery of oxygen by the epoxidadon catalyst to one face of the olefin in preference to the other. This usage extends to chiral allylic alcohols (primarily the 1-substituted allylic alcohols) when the focus of the discussion is on face selection in the epoxidation process. Diastereoselectivity is used in the discussion of kinetic resolution when the generation of diastereomeric compounds is emphasized. 

Several other allylic alcohols with primary C-2 substituents have been epoxidized with very good results (entries 7-10, 14). Epoxy alcohols have been obtained with 95-96% ee and, when the catalytic version of the reaction is used, as in entry 10, the yield is excellent. When the C-2 substituent is more highly branched, as in entries 11-13, there may be some interference with high enantiofacial selectivity by the bulky group, because the enantioselectivity in two cases (entries 11 and 12) is 86%. Another example that supports this possibility of steric interference to selective epoxidation is summarized in Eq. 6A.3a [39]. In this case the optically active allylic alcohol 12, (3/ )-3,7-dimethyl-2-methylene-6-penten-l-ol, was subjected to epoxidation with both antipodes of the Ti-tartrate catalyst. With (+)-DIPT, enantiofacial selectivity was 96 4... 

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