Allylic Substitution (chapter 20)

• allylic substitutions must be catalyzed by complexes containing ligand that create a sufficiently electron poor allyl complex for nucleophilic attack to occur.
• The activity of electrophilie: allylic carbamate > phosphate > acetate, other nucleophiles including sulfonate, nitro, amine, acetal, geminal diacetate, halides. Especially, the allylic carbamate and vinyl epoxide/azaridine could in-situ generate bases (alkoxide).
• stable nucleophiles: retention of configuration; instable nucleophiles: inversion of configuration.
• usually, the reaction employ soft nucleophiles, such as beta-dicarbonyl compounds. Nucleophile-electrophile tethered substrates could be used in these reactions.
• Palladium and Nickel catalyzed reaction prefer linear (alpha-substitution) products, while other metals, including molybdenium, ruthenium, rhodium, tungsten, et al, trend to give branch product (gamma-substitution).
• Stable nucleophiles usually nucleophlic attack on allylic-metal complex (configuration retention), while the instable nucleophiles prefer to perform transmetallation, which followed by reductive elimination (configuration inversion). etta3-etta1-etta3 conversion is the very reason for the lose of stereoselectivity, when the rate of nucleophlic attack is much slower than these conversion.
• Although the palladium catalyzed reaction prefer the alpha position substitution, the regioselectivity could still be controlled by ligands, which generate a C+ center at more substituted position by making complex sufficient positive.
• Heteroatoms prefer branched product. However, amine participated reactions may give linear product as thermodynamic product. The resulting allylic amine is still a substrate for allylic substitution.
• The memory effect of Pd-MOP complex could retain stereocenter of substrates.
• Copper-catalyzed reaction usually use monoalkyl cuporate as intermediate. The reaction has high gamma-selectivity for orbital interaction reason. Besides, this type of reaction prefer to use main-group organometal reagent as nucleophlies.