Acylsilanes in Organic Synthesis Techniques

Acylsilanes, characterised by a silyl substituent bound to a carbonyl carbon, have emerged as versatile reagents in modern synthetic chemistry. Their unique reactivity stems from the electron-donating properties of the silicon centre, which facilitates cleavage of the carbon–silicon bond under thermal, photochemical or Lewis acid-promoted conditions. Central to acylsilane chemistry is the Brook rearrangement, in which a 1,2-shift of the silyl group to the oxycarbon generates a siloxycarbene intermediate capable of undergoing diverse bond-forming reactions. As a result, acylsilanes participate in carbon–carbon and carbon–heteroatom bond formation via cycloaddition, insertion and sigmatropic rearrangement pathways. Transition-metal catalysis has harnessed acylsilanes as carbene precursors for palladium-catalysed carbonylative cycloaddition, yielding lactams and complex ring systems. Photochemical strategies exploit excited-state energy transfer to suppress decomposition and effect cascade cyclisations. Organocatalytic and non-enzymatic asymmetric methods have delivered chiral acylsilane derivatives with high enantioselectivity. Beyond methodology, acylsilane transformations have been applied to the late-stage functionalisation of natural products and pharmaceutical scaffolds, highlighting their global significance in sustainable and selective synthesis.

Research from Nature Portfolio

Recent studies have demonstrated that acylsilanes can serve as precursors for catalytic Fischer–carbene intermediates, enabling carbonylative cycloaddition with imines to furnish highly substituted β-lactam derivatives. A key siloxycarbene–palladium complex was isolated and structurally characterised, illuminating the reaction mechanism and showcasing broad substrate scope. In parallel, energy-transfer photocatalysis has been exploited to achieve cascade cyclisation of alkene-tethered acylsilanes and allylic sulfones. By employing a photocatalyst with lower triplet energy, undesired photodecomposition is inhibited, allowing efficient construction of cyclopentanol frameworks bearing fused or bridged rings. Additionally, non-enzymatic catalytic asymmetric cyanation of acylsilanes has been realised using a chiral Lewis base and trimethylsilyl cyanide, affording optically active acylsilane cyanohydrins with high enantioselectivity. A subsequent development established robust conditions for protecting these sensitive intermediates, thereby facilitating their use in downstream synthesis.

Acylsilanes in Organic Synthesis Techniques publication trend

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

Technical terms

Acylsilane: An organosilicon compound featuring a silyl group directly attached to a carbonyl carbon.

Brook rearrangement: A 1,2-shift of the silyl group from carbon to oxygen, generating a siloxycarbene intermediate.

Siloxycarbene: A nucleophilic carbene species formed upon migration of a silyl group to the adjacent carbonyl oxygen.

Carbonylative cycloaddition: A process combining carbonyl insertion and cycloaddition to construct ring systems from acyl precursors and unsaturated partners.

Photocatalysis: The acceleration of chemical reactions through light-induced excitation of a catalyst, enabling novel reaction pathways under mild conditions.

References

1. Catalytic synthesis of β-lactam derivatives by carbonylative cycloaddition of acylsilanes with imines via a palladium Fischer-carbene intermediate. Nature Catalysis (2024).
2. Intramolecular photochemical [2 + 1]-cycloadditions of nucleophilic siloxy carbenes. Chemical Science (2022).
3. Cascade cyclization of alkene-tethered acylsilanes and allylic sulfones enabled by unproductive energy transfer photocatalysis. Nature Communications (2022).
4. Synthesis and Photochemistry of Tris(trimethoxysilyl)acyl-silanes and 1,4-Tetrakis(silyl)-1,4-bisacylsilanes. Organometallics (2024).
5. Non-enzymatic catalytic asymmetric cyanation of acylsilanes. Communications Chemistry (2022).
6. Friedel–Crafts Reaction of Acylsilanes: Highly Chemoselective Synthesis of 1-Hydroxy-bis(indolyl)methanes and 1-Silyl-bis(indolyl)methanes Derivatives. Molecules (2023).