Superbase-Promoted Organic Synthesis of Acetylenic Compounds

Superbases—conventionally defined as bases stronger than hydroxide—have transformed the preparation and manipulation of acetylenic compounds by enabling the deprotonation of weakly acidic sp-hybridised C–H bonds under mild conditions. Typical superbase systems include alkali metal alkoxides or amides in polar aprotic media (for example, potassium tert-butoxide in dimethyl sulfoxide), phosphazene bases and proton-sponges. Their exceptional basicity permits rapid formation of alkynyl anions, which may be coupled to electrophiles, engaged in cycloadditions or induced to undergo rearrangements such as Favorsky and retro-Favorsky processes. Advances in superbase-promoted methodologies have unlocked access to functionalised alkynes with applications in drug discovery, agrochemicals and materials science. Control of solvent, temperature and moisture content has emerged as a critical parameter to steer selectivity between allenes and alkynes, while mechanistic studies—both experimental and computational—are illuminating the interplay between solvation and acid–base equilibria that underlie these transformations.

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Superbase-Promoted Organic Synthesis of Acetylenic Compounds publication trend

The graph below shows the total number of articles in superbase-promoted organic synthesis of acetylenic compounds across all publications each year (not limited to Nature Index journals).

Technical terms

Superbase: An exceptionally strong base capable of deprotonating very weak acids such as terminal alkynes under mild conditions.

Acetylenic compound: An organic molecule containing a carbon–carbon triple bond (alkyne), often serving as a versatile building block.

Favorsky reaction: A base-catalysed nucleophilic addition of alkynyl anions to carbonyl compounds to form acetylenic alcohols.

Retro-Favorsky reaction: The reverse fragmentation of acetylenic alcohols under strong basic conditions to regenerate alkynes and carbonyl fragments.

References

1. Unexpected Decarbonylation of Acylethynylpyrroles under the Action of Cyanomethyl Carbanion: A Robust Access to Ethynylpyrroles. Molecules (2023).
2. Quantum Chemical Investigations of the Mechanisms of Carbo- and Heterocycles Assemblies Based on Acetylenes Reactions in Superbasic Media. Russian Journal of Organic Chemistry (2023).
3. 1-Methylimidazole as an Organic Catalyst for [3+3]-Cyclodimerization of Acylethynylpyrroles to Bis(acylmethylidene)dipyrrolo[1,2-a:1′,2′-d]pyrazines. Catalysts (2022).
4. Why base-catalyzed isomerization of N-propargyl amides yields mostly allenamides rather than ynamides. Beilstein Journal of Organic Chemistry (2015).
5. Choosing a solvation model for simulating reactions in KOH(KOBu t )/DMSO superbasic media. Journal of Physics Conference Series (2021).