Nucleophiles prochiral

It should be noted that Trost s DPPBA-derived ligand 21 possesses considerable utility in many other situations of allylic substitution, for example with substrates which are cyclic or which possess enantiotopic leaving groups, or with prochiral nucleophiles.1171... 

Nitroalkanes react with allylic carbonates in the presence of iridium catalysts [83]. However, nitroalkanes are prochiral, and products are formed with poor diastereo-selectivity. Nitroalkanes and other prochiral nucleophiles are discussed further in Sect. 6. 

The scope of reactions catalyzed by metalacychc iridium-phosphoramidite complexes is remarkably broad, but reactions with some substrates, such as allylic alcohols, prochiral nucleophiles, branched allylic esters, and highly substituted allylic esters, that would form synthetically valuable products or would lead to simpler symthesis of reactants occur with low yields and selectivities. In addition, iridium-catalyzed allylic substitution reactions are sensitive to air and water and must be conducted with dry solvents under an inert atmosphere. Several advances have helped to overcome some, but not aU of these challenges. 

Williams group observed low enantioselectivities for the Michael addition of a prochiral nucleophile, ethyl 2-cyanopropionate 623, to methyl vinyl ketone 624 catalyzed by chiral platinum complexes (Scheme 8.196)." The NMR analysis indicated that these cationic Pt complexes act as Lewis acids toward nitriles. The X-ray crystal structure as well NMR analysis showed that the solvent ligand that is readily displaced by an organic substrate is situated cis to the nitrogen donor in the Pt complex and, therefore, is in a chiral pocket created by the oxazoline ring. 

Allylic alkylations using a benzophenone imine of glycine methyl ester as a prochiral nucleophile and chiral phosphine ligands on palladium produced optical yields up to 57% (equation 354).436... 

When a prochiral nucleophile is reacted with 1,3-disubstituted allylic systems, the issue of diastereo- as well as enantioselectivity arises. In the alkylation of a tetralone, both the acyclic... 

In general, reactions involving prochiral nucleophiles are rare however, examples using activated dicarbonyl compounds and carbonyl compounds that can form only a single enolate under the base-mediated reaction conditions have recently been reported. 

Attack by different enantiofaces of prochiral nucleophiles if the nucleophile is an enolate ion, it has two prochiral faces that could attack the i(]3-allyl ligand attack from the top face will lead to one enantiomer and attack from the bottom face will lead to the other (step c, Scheme 12.10a or b). 

A two component catalyst system has provided promising results in the alkylation of a 7t-allyl moiety with a prochiral nucleophile (Scheme 44). 

Kagan was the first to study reactions in which enantioselectivity at a prochiral nucleophile was examined. In the reaction of 2-acetyltetralone with allylic ethers in the presence of a chiral DIOP-Pd catalyst, Eq. (10), the allylated products were obtained with ee s of only 10% [34]. 

This reinforced the expectation that simple chiral ligands would not be able to produce useful levels of enantioselectivity at the nucleophilic center. Since then a number of workers have devised chiral ligands specifically designed for inducing enantioselectvivity at the nucleophilic center of prochiral nucleophiles in allylic alkylations [35]. In 1982 Kumada and coworkers constructed a series of lig-... 

A-(Diphenylmethylene)glycine t-butyl ester (t-butyl glycinate-benzophenone Schiff base) (171) is a reactive prochiral nucleophile and a-allyl-a-amino acids can be prepared by allylation and hydrolysis of the allylated product. Asymmetric allylation of 171 with cinnamyl acetate (41) afforded 172 regioselec-tively with high % ee when the reaction was carried out in presence of achiral phosphite P(OPh)3, and a ehiral phase-transfer catalyst of alkaloid [0-allyl-(9-anthracenylmethyOcinchonidinium iodide] [65,66]. 

In addition to coupling reactions that occur with aryl and vinyl nucleophiles and electrophiles, coupling reactions that occur with sp -hybridized nucleophiles or electrophiles have been developed. These reactions include those that form tertiary and quaternary stereocenters from racemic or prochiral nucleophiles, as shown in Equation 19.4. Substitution reactions at propargylic and benzylic electropliiles have also been reported, and several groups have reported in recent years progress in metal-catalyzed substitutions of alkyl electrophiles, including enantioselective substitutions of aliphatic organic halides. 

Finally, these reactions can be conducted with prochiral nucleophiles. In this case, shown as Equation F of Scheme 20.10, a stereocenter is generated at the nucleophile, instead of the electrophile. If the nucleophile and the electrophile are both prochiral, then control of both absolute and relative stereochemistry is necessary. 

A final approach to enantioselective allylic substitution is the reaction of prochiral nucleophiles with allylic esters. In this case, the stereocenter is not generated on the allyl unit it is generated at the nucleophilic carbon. This chemistry has been conducted with cyanoesters and related unsymmetrical stabilized carbon nucleophiles, including azlactones, which are a protected form of ammo acids. This generation of a stereocenter in the nucleophile is thought to be particularly challenging because the position at which the stereocenter is formed is further from the metal than it is in reactions that form a stereocenter at the allyl group. 

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