Palladium-catalyzed asymmetric allylic alkylation (AAA) has proven to be an exceptionally powerful method for the efficient construction of stereogenic centers. In sharp contrast to many other catalytic methods, AAA has the ability to form multiple types of bonds (C–C, C–O, C–S, C–N) with a single catalyst system.
The Trost group at Stanford University has pioneered the use of C-2 symmetric diaminocyclohexyl (DACH) ligands in AAA, allowing for the rapid synthesis of a diverse range of chiral products with a limited number of chemical transformations. Reactions are typically high yielding, and excellent levels of enantioselectivity are observed.
In early examples of this methodology, Trost and co-workers demonstrated that diesters are competent nucleophiles for the deracemization of cyclic allylic acetates, to afford chiral malonate derivatives. Since that time, soft carbon nucleophiles such as barbituric acid derivatives, β-keto esters, nitro compounds, and many others have been employed in AAA for assembly of tertiary and quaternary asymmetric centers.
Carbon-oxygen bond-forming reactions using palladium-catalyzed asymmetric allylic alkylation have been well demonstrated in numerous natural product syntheses. Alcohols, carboxylates, and hydrogencarbonates have all been employed as O-nucleophiles.
A formidable challenge in asymmetric synthesis is the stereocontrolled construction of carbon-nitrogen bonds. Nitrogen nucleophiles such as alkylamines, azides, amides, imides, and N-heterocycles have all been employed in asymmetric allylic alkylation reactions.
The mechanism of molybdenum-catalyzed AAA reaction is presumed to be distinctly different from the analogous Pd-catalyzed reaction, and in some cases, levels regio-, enantio- and diastereoselectivity enhanced relative to the palladium-catalyzed reaction.
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