Prochiral nucleophiles, allylation

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. 

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... 

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]. 

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. 

Scheme 12.78 Mo-catalyzed asymmetric allylic alkylations with prochiral nucleophiles [173, 179].

The use of a prochiral nucleophile in allylic substitution reactions provides an additional opportunity for asymmetric indnction. Allyl acetate itself can be used as the electrophilic partner and the new stereogenic center is positioned further away from the allyl group (Scheme 28). 

When prochiral nucleophiles are employed with more complex allyl electrophiles, there is the possibility of forming two sterocenters in the product (Scheme 32). For example, imino phosphonate 147 has been used as the nucleophile in the reaction with allyl acetate 4. The control of enantioselectivity at the benzylic position is very high, but there is lower relative stereocontrol at the newly formed stereocenter a to the phosphonate group.f ... 

A comprehensive review of asymmetric allylic alkylation since our initial publication would be beyond the scope of this accotmt. Instead, we will highlight the use of prochiral nucleophiles in asymmetric allylic alkylation reactions. Unlike the majority of asymmetric allylic alkylation reactions, reactions involving prochiral nucleophiles generate a stereocenter on the nucleophile. Major advances have occurred with regard to the classes of prochiral nucleophiles that can be used in these reactions. 

Scheme 17 Non-ketone derived prochiral nucleophiles in asymmetric allylic alkylation...

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