Fluoroalkylacylsilanes as Novel Ambiphilic Donor–Acceptor Carbene Precursors

ConspectusCarbenes, as highly reactive intermediates, have emerged as pivotal tools in organic synthesis, catalysis, and materials science due to their versatile reactivity and broad applicability. Among the diverse classes of carbenes, donor-acceptor carbenes (DACs) have attracted significant attention owing to their unique electronic properties and exceptional reaction selectivity. The distinctive reactivity of DACs arises from the synergistic electronic interplay between electron-withdrawing and electron-donating groups attached to the carbene center, enabling a wide array of transformations. These attributes have established DACs as indispensable building blocks for constructing complex molecular architectures and achieving precise control over chemical transformation.This Account highlights our recent advancements in the development of fluoroalkylacylsilanes as novel precursors for DACs. Under photocatalytic conditions, these fluoroalkylacylsilanes generate fluoroalkyl siloxycarbenes via a radical Brook rearrangement. The fluoroalkyl group, known for its strong electron-withdrawing properties, imparts electrophilic characteristics, while the siloxyl group stabilizes the carbene center. Together, these functionalities render fluoroalkylacylsilanes ideal candidates for the generation of DACs, providing a versatile platform for a wide range of novel transformations, including cycloadditions, bond insertions, and the construction of new molecular structures.First, we developed a visible-light-induced, organocatalyzed [2 + 1] cyclization of alkynes and trifluoroacetylsilanes, leading to the synthesis of cyclopropenols. Mechanistic studies provided compelling evidence for the involvement of triplet carbene intermediates in this reaction, demonstrating the utility of DACs in the synthesis of highly functionalized cyclic compounds. Second, we explored cyclopropanation reactions and elucidated the diastereoselective transfer of trifluoroacetylsilane-derived DACs to alkenes. Density functional theory (DFT) calculations revealed key insights into the origins of the observed diastereoselectivity, offering a molecular-level understanding of the stereochemical outcomes. Additionally, we extended the scope of our reactions to include organoboronic esters, enabling the divergent synthesis of fluoroalkyl ketones. By modulating the reactivity of the in situ-generated organoboronate complexes─formed through the reaction of DACs with organoboronic esters─we achieved selective synthesis of both fluorine-maintaining and defluorinated ketones. This transition-metal-free approach is operationally simple and compatible with a broad range of substrates, including aryl, alkenyl, and alkyl boronic esters. Beyond cyclization and C-B bond functionalization, we applied our novel DACs to C(sp²)-H functionalization reactions of 1,3-azoles. Mechanistic investigations suggest that the success of these reactions stems from the dual role of trifluoroacetylsilanes under photocatalytic conditions: they not only generate carbenes that participate in cyclopropanation but also produce biradicals that facilitate the ring-opening aromatization of the in situ-generated fused cyclopropanes.We anticipate that our work on fluoroalkylacylsilanes as ambiphilic donor-acceptor carbene precursors will lay the groundwork for further advancements in the use of functionalized acylsilanes in carbene chemistry. These developments are expected to inspire new strategies for the design of DACs and expand the utility of silanes in complex synthetic transformations, opening new avenues for the construction of intricate molecular architectures.