Ligand-controlled stereoselective reaction

Reactions through chelated TS Reactions of a- or (3-oxy-substituted aldehydes often show chelation-controlled stereoselectivity with Lewis acids that can accommodate five or six ligands. Chelation with substituents in the allylic reactant can also occur. The overall stereoselectivity depends on steric and stereoelectronic effects in the chelated TS. 

This type of additive (or ligand) control of stereoselectivity has three advantages. First of all, after the reaction has been completed, the chiral additive can be separated from the product with physical methods, for example, chromatographically. In the second place, the chiral additive is therefore also easier to recover than if it had to be first liberated from the product by means of a chemical reaction. The third advantage of additive control of enantioselectivity is that the enantiomerically pure chiral additive does not necessarily have to be used in stoichiometric amounts catalytic amounts may be sufficient. This type of catalytic asymmetric synthesis, especially on an industrial scale, is important and will continue to be so. 

In 1981, a stereoselective palladium-catalyzed 1,4-diacetoxylation of conjugated dienes was reported [51-53]. By ligand control it was possible to direct the reaction to either 1,4-trans- or 1,4-cw-diacetoxylation (Scheme 8-7). 

Kochi s study of the copper salt-catalyzed oxidation of butenes by peresters (17) is interesting because the role of a ligand in controlling stereoselectivity was clearly demonstrated. This reaction, which involves the oxidation of allylic radicals by cupric ion, results in the formation of high yields of allylic ester in which the double bond is terminal, and it is described as occurring within a metal complex. When phenanthroline... 

Although many of the effects that control stereoselectivity arc known, general rules for the choice of chiral ligands and their effects on catalytic activity, measure and direction of stereoselectivity cannot be given. Several attempts have been made to establish rules for individual reaction types. These are discussed in the corresponding section. 

Chiral samarium (II) complexes have also been applied towards the hydrodimerization of acrylic acid amides [16]. Such reactions involve the ligand-controlled dimerization of conjugated ketyl radicals in the enantioselective formation of 3,4-tra .y-disubstituted adipamides (Eq. 11). Yields were mainly low, often under 40% and enantiocontrol was modest with selectivities ranging from around 50-85% ee. A nine-membered chelated transition state 37 is used to rationalize the stereoselectivity of the dimerization where the ligand-bound conjugated ketyl radicals are oriented cis to each other on the metal assuming an octahedral geometry. 

With the above-mentioned new developments, theoretical calculations should be able to use more realistic models of elementary reactions and homogeneous catalysts and utilize many important aspects of transition-metal-catalyzed reactions, including the role of different ligands, the role of different transition-metal atoms, chemo-, and stereoselectivity, and other factors controlling the reactions. Predictions of catalytic reactivities based on theoretical calculations should be forthcoming. Collaboration between experimentalists and theoreticians is strongly encouraged. 

Either ammonia or a variety of amine substrates can be used to prepare the product 2, widely called a Betti base. Various substitution patterns are tolerated on both the naphthol and aryl aldehyde component. While the reaction was classically performed in ethanol, a variety of solvents, and using the substrates neat are also possible. Increased rates have been observed using acid catalysis. The reaction results in a product 2 with a benzylic chiral center, which as such can be resolved into its enantiomers. Alternatively, chiral amines can be used to control the stereoselectivity of the process. Enantiomerically pure Betti bases have shown potential as chiral auxiliaries and as ligands in asymmetric reactions. ... 

Abstract The basics of stereoselective reactions and reaction stereochemistry—the relation of stereoselectivity to the topology of tetrahedral and planar units in organic molecules—are discussed. The kinetic control of enantioselective reactions and characteristics of enantioselective and diastereoslective reactions is presented. Asymmetric syntheses are exemplified by the hydrogenation of C=0 and C=NR bonds in prochiral substrates catalyzed by organometallic complexes with chiral phosphine ligands. The mechanism of asymmetric alkylation of stabilized carban-ions in specifically designed chiral substrates and the practicability of this mefliod in the preparation of optically pure a-alkyl carboxylic acids are discussed. The synthetic approach to chiral auxiliaries and importance of recycling are presented. 

Ananikov VP, Orlov NV, Kabeshov MA, Beletskaya IP, Starikova ZA. Stereoselective synthesis of a new t)fpe of 1, 3-dienes by ligand-controlled carbon-carbon and carbon-heteroatom bond formation in nickel-catalyzed reaction of diaryldichalcogenides with alkynes. Organometallics 2008 27 4056 061. 

An interesting way to control the stereoselectivity of metathesis-reactions is by intramolecular H-bonding between the chlorine ligands at the Ru-centre and an OH-moiety in the substrate [167]. With this concept and enantiomerically enriched allylic alcohols as substrates, the use of an achiral Ru-NHC complex can result in high diastereoselectivities like in the ROCM of 111-112 (Scheme 3.18). If non-H-bonding substrates are used, the selectivity not only decreases but proceeds in the opposite sense (product 113 and 114). 

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