External chiral ligands

Table 5. Conjugate Addition to Acyclic Enones with External Chiral Ligands O, O...

To date, direct asymmetric synthesis of optically active chiral-at-metal complexes, which by definition leads to a mixture of enantiomers in unequal amounts thanks to an external chiral auxiUary, has never been achieved. The most studied strategy is currently indirect asymmetric synthesis, which involves (i) the stereoselective formation of the chiral-at-metal complex thanks to a chiral inductor located either on the ligand or on the counterion and then (ii) removal of this internal chiral auxiliary (Fig. 4). Indeed, when the isomerization of the stereogenic metal center is possible in solution, in-... 

It may be concluded from the different examples shown here that the enantioselective copper-catalyzed allylic substitution reaction needs further improvement. High enantioselectivities can be obtained if chirality is present in the leaving group of the substrate, but with external chiral ligands, enantioselectivities in excess of 90% ee have only been obtained in one system, limited to the introduction of the sterically hindered neopentyl group. 

An asymmetric Horner-Wadsworth-Emmons reaction has been developed which uses an external chiral ligand to avoid the need to prepare chiral phosphonate derivatives. ... 

The bis(oxazoline) S, 5)-(115) has been used as an external chiral ligand to induce asymmetric diastereoselective lithiation by r-BuLi during [2,3]-Wittig rearrangement of achiral substrates, (fj-crotyl propargylic ethers.It is believed that the enantios-electivity is determined predominantly at the lithiation step. 

VIII. REACTIONS MEDIATED BY AN EXTERNAL CHIRAL LIGAND A. Basic Concept... 

The C2 symmetric chiral diether 28" and the naturally occurring chiral diamine, (—)-sparteine (29), have been the most successful external chiral ligands for asymmetric conjugate addition of organolithium reagents. The rest of this review highlights organolithium addition, which is mediated or sometimes catalyzed by 28 or 29. 

AG small) this situation may arise from a chiral ligand external to the carbanion, or because there are additional stereocenters in the carbanion. 

Figure 2b shows the other extreme, whereby the rate of epimerization is fast relative to the rate of substitution. In this case, Curtin-Hammett kinetics apply, and the product ratio is determined by AAG. In the specific case of organolithium enantiomers that are rendered diastereomeric by virtue of an external chiral ligand, such a process may be termed a dynamic kinetic resolution. Both of these processes are also known by the more general term asymmetric transformation One should be careful to restrict the term resolution to a separation (either physical or dynamic) of enantiomers. An asymmetric transformation may also afford dynamic separation of equilibrating diastereomers, but such a process is not a resolution. "... 

When all chiral units have unknown configuration, both the relative and absolute configuration need to be determined. This situation is encountered in many asymmetric reactions performed under the influence of chiral catalysts or external chiral ligands. 

The aldol reaction of 3-pentanone with acetaldehyde provides an example52 of control by an external chiral ligand 9. The relative configuration at the newly created stereogenic centers (syn vs. anti) of the adduct 10 was determined by NMR, while the absolute configuration was assigned by a chemical correlation (see p 452)101 -I02. 

For a recent review on asymmetric synthesis utilizing external chiral ligands see K. Tomioka, Synthesis 1990, 541. 

The catalytic asymmetric Mannich reaction of lithium enolates with imines was reported in 1997 using an external chiral ligand [36]. First, it was found that reactions of lithium enolates with imines were accelerated by addition of external chiral ligands. Then, it was revealed that reactions were in most cases accelerated in the presence of excess amounts of lithium amides. A small amount of a chiral source was then used in the asymmetric version [(Eq. (8)], and chiral ligands were optimized to achieve suitable catalytic turnover [37]. 

Stoichiometric and catalytic asymmetric reactions of lithium enolate esters with imines have been developed using an external chiral ether ligand that links the components to form a ternary complex.36 The method affords /i-lactams in high enantiomeric excess. 

Radical Reaction by Using External Chiral Ligands.119... 

---