Catalytic Asymmetric Synthesis of Alkynes and Enol Esters

The catalytic asymmetric synthesis of alkynes and enol esters encompasses a suite of methods that employ chiral transition-metal complexes to forge carbon–carbon triple bonds and install ester functionalities with high stereochemical fidelity. Strategies range from direct enantioselective conjugate additions of alkynyl nucleophiles to α,β-unsaturated acceptors, through to hydroacyloxylation of alkynes that yields enol esters in one step. Sequential catalysis combines cross-coupling of terminal alkynes with acetylenic partners followed by enantioselective reduction, allowing access to a broad array of chiral β-alkynyl carbonyl derivatives. Key to these processes are bespoke chiral ligands, synergistic ligand–metal interactions and carefully engineered directing groups, which together govern both regioselectivity and enantioselectivity. Advances in ligand design, mechanistic insight and catalyst development have extended substrate scope to include heteroaromatic acids, internal alkynes and functionalised enyne scaffolds. The resulting chiral products have found application as precursors to natural products, pharmaceutical candidates and advanced materials, underscoring the global significance of these atom-economical, tunable methodologies.

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Catalytic Asymmetric Synthesis of Alkynes and Enol Esters publication trend

The graph below shows the total number of articles in catalytic asymmetric synthesis of alkynes and enol esters across all publications each year (not limited to Nature Index journals).

Technical terms

Catalytic asymmetric synthesis: Use of chiral catalysts to produce enantiomerically enriched products.

Alkynes: Organic molecules containing a carbon–carbon triple bond.

Enol esters: Esters derived from enol tautomers, often formed by addition of carboxylic acids to alkynes.

Enantioselectivity: Preference for formation of one enantiomer over its mirror image in a chiral reaction.

Regioselectivity: Preference for reaction at one position on a molecule over other possible positions.

Chiral ligand: A ligand possessing asymmetry that induces chirality in a metal catalyst’s coordination sphere.

References

1. Metal-Catalyzed Intra- and Intermolecular Addition of Carboxylic Acids to Alkynes in Aqueous Media: A Review. Catalysts (2017).
2. Highly enantioselective copper( i )-catalyzed conjugate addition of 1,3-diynes to α,β-unsaturated trifluoromethyl ketones. Chemical Communications (2015).
3. Asymmetric synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives via sequential palladium and copper catalysis. Chemical Science (2016).
4. Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes. ACS Catalysis (2022).