Asymmetric Allylic Transformations in Organic Synthesis

Asymmetric allylic transformations encompass a suite of reactions in which an allylic substrate undergoes selective bond formation to generate enantioenriched products. Central to these processes is the formation of a metal–π-allyl intermediate, which can engage nucleophiles or electrophiles under chiral catalysis to build carbon–carbon or carbon–heteroatom bonds with high stereocontrol. Over the past decade, advances in catalyst design, reaction engineering and mechanistic understanding have expanded the scope of allylic alkylations, allylic arylations, allylborations and related processes. Tailored ligands and dual‐catalytic systems now allow precise control of regio- and enantioselectivity even in challenging acyclic and densely functionalised substrates. These developments have found broad application in the synthesis of natural products, pharmaceuticals and fine chemicals, where the assembly of chiral centres in a single step enhances step economy and reduces waste.

Research from Nature Portfolio

Recent studies have uncovered an unprecedented migratory behaviour of π-allyl intermediates in nickel-catalysed allylic arylations. Under dual catalysis with a lanthanide Lewis acid, the π-allyl nickel species undergoes sequential β-hydride elimination and reinsertion to “walk” along a carbon chain, delivering arylated products with strict regio- and stereocontrol from 1,n-enol substrates. The broad substrate tolerance and mechanistic insight provided by computational studies highlight new pathways for remote functionalisation.

In parallel, enantioconvergent Suzuki–Miyaura-type arylations of acyclic allylic electrophiles have been realised through chelation-enabled selectivity control. By exploiting the coordinating ability of an ester functionality, reactions of racemic precursors with aryl boronic acids proceed with high chemo-, regio- and enantioselectivity. This strategy has been applied to the efficient synthesis of bioactive molecules, including clinically relevant antidepressants and natural products.

Asymmetric Allylic Transformations in Organic Synthesis publication trend

The graph below shows the total number of articles in asymmetric allylic transformations in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

π-allyl complex: A reactive intermediate in which an allylic fragment binds to a metal centre through a delocalised three-carbon unit, facilitating subsequent bond-forming events.

Enantioconvergent transformation: A process that converts both enantiomers of a racemic mixture into a single enantiomer of the product.

Regioselectivity: The preferential formation of a bond at one position over other possible positions in a substrate.

Enantioselectivity: The preferential formation of one enantiomer over its mirror image in a chiral reaction.

Allylboration: The addition of an allylic boron species to an electrophile, typically a carbonyl or imine, to form a new C–C bond with control over stereochemistry.

References

1. Migratory allylic arylation of 1,n-enols enabled by nickel catalysis. Nature Communications (2023).
2. Chelation enables selectivity control in enantioconvergent Suzuki–Miyaura cross-couplings on acyclic allylic systems. Nature Chemistry (2024).
3. Ligand-enabled Ir-catalyzed intermolecular diastereoselective and enantioselective allylic alkylation of 3-substituted indoles. Chemical Science (2015).
4. Synthesis of Adjacent Quaternary Stereocenters by Catalytic Asymmetric Allylboration. Journal of the American Chemical Society (2015).
5. Ligand-controlled diastereodivergent, enantio- and regioselective copper-catalyzed hydroxyalkylboration of 1,3-dienes with ketones. Chemical Science (2019).