Addition reactions chiral ligands

Over the last five years, we have designed, synthesized, and applied new ligands for asymmetric 1,2- and 1,4-addition reactions. Suitable ligands were found for the addition of alkyl-, aryl-, and alkenylzinc reagents to a,(3-unsaturated aldehydes and ketones, a-branched and unbranched aliphatic aldehydes, and imines. Although some substrates such as ketones and other carbonyl compounds have remained a challenge, we believe that this system provides an excellent entry into various classes of chiral intermediates. Application of these synthesized complex molecules is the current pursuit in our laboratories. 

Asymmetric Aziridination of Alkenes. The copper-catalyzed aziridination reaction can be rendered enantioselective by the addition of chiral ligands. The first example of an enantioselective aziridination of an alkene employed the bis(oxazoline) ligand (4) (R = f-Bu) and copper(I) trifluoromethanesulfonate as the metal catalyst (eq 14). This catalyst system affords the aziridine in 97% yield and 61% ee. Other reports have appeared subsequently regarding the extended scope of this reaction. " Important contributions to this area include the copper/bis-(oxazoline)-catalyzed aziridination of aryl acrylate esters (eq 15) and the copper/bis(imine)-catalyzed aziridination of cyclic cis-alkenes with the bis(imine) ligand (5) (eqs 16 and 17). ... 

In an extension of this work they developed a catalytic version of the reaction in which the chiral ligand (J ,J )-diisopropyltartrate (DIPT) was applied in 20 mol% [77]. In spite of the reduction of the amount of the chiral ligand similar high enantioselectivities of up to 93% ee were obtained in this work. The addition of a... 

Another important reaction associated with the name of Sharpless is the so-called Sharpless dihydroxylation i.e. the asymmetric dihydroxylation of alkenes upon treatment with osmium tetroxide in the presence of a cinchona alkaloid, such as dihydroquinine, dihydroquinidine or derivatives thereof, as the chiral ligand. This reaction is of wide applicability for the enantioselective dihydroxylation of alkenes, since it does not require additional functional groups in the substrate molecule ... 

A remarkable effect of the reaction temperature on the enantioselectivity of the addition of butyllithium to benzaldehyde was found with polystyrene-bound cvs-enofo-S-dimethylamino -(benzyloxy)bornane (8)12. When the soluble monomeric ligand 9 was tested, the enantioselectivity increased with decreasing temperature (53% ee at — 78 C). In contrast, the polymer-bound chiral additive 8 showed an optimum at — 20 C (32% ee). Although the enantioselectivity of this addition reaction is low, an advantage of a polymer-bound chiral auxiliary is that it can be removed by a simple filtration. 

Abstract The dirhodium(II) core is a template onto which both achiral and chiral ligands are placed so that four exist in a paddle wheel fashion around the core. The resulting structures are effective electrophilic catalysts for diazo decomposition in reactions that involve metal carbene intermediates. High selectivities are achieved in transformations ranging from addition to insertion and association. The syntheses of natural products and compounds of biological interest have employed these catalysts and methods with increasing frequency. 

In addition to the enhanced rate of hydroalumination reactions in the presence of metal catalysts, tuning of the metal catalyst by the choice of appropriate ligands offers the possibility to influence the regio- and stereochemical outcome of the overall reaction. In particular, the use of chiral ligands has the potential to control the absolute stereochemistry of newly formed stereogenic centers. While asymmetric versions of other hydrometaUation reactions, in particular hydroboration and hydrosi-lylation, are already weU established in organic synthesis, the scope and synthetic utiHty of enantioselective hydroalumination reactions are only just emerging [72]. 

In addition, Bryce and Chesney have developed chiral oxazolines linked to tetrathiafulvalene in order to use these ligands as redox-active ligands. When applied to the test reaction, these ligands gave only low enantioselec-tivities (<21% ee), as shown in Scheme 1.32. 

---