C–O Bond Silylation Catalyzed by Iron: A General Method for the Construction of Csp²–Si Bonds

Abstract

The iron-catalyzed construction of Csp 2 −Si bonds via unreactive C−O bonds possesses a challenging topic in organic chemistry. Herein we report an iron-catalyzed silylation of aryl and alkenyl carbamates via C−O bond activation. This protocol features high efficiency and a broad substrate scope, enabling the late-stage silylation of biorelevant compounds and thus providing a good method to access valuable motifs in medicinal chemistry. Moreover, this protocol enables orthogonal transformations of phenol derivatives and also allows for the synthesis of multisubstituted arenes through the carbamate group as the directing group.I ron catalysts have been widely used in cross-coupling reactions owing to their cheapness, abundance, and nontoxicity. 1 To facilitate the oxidative addition in ironcatalyzed cross-coupling reactions, a highly reactive, low-valent iron species always needs to be generated through sacrificial organometallic reagents via reductive elimination in situ. 2 Consequently, these reactions are mostly limited to the formation of C−C bonds through classical cross-coupling reactions, 3 and the iron-catalyzed construction of C− heteroatom bonds has lagged. 4 Organosilicon compounds are important reagents that are widely employed in organic synthesis, material science, as well as medicinal chemistry. 5 However, iron-catalyzed cross-coupling reactions to construct C−Si bonds have been less developed. 6,7 It is of great interest to develop an organometallic reagent-free and efficient ironcatalyzed method for the construction of C−Si bonds.Compared with organohalides, oxygen-based electrophiles, such as phenol and ketone derivatives, have become increasingly more attractive as the coupling partners. 8 Not only are phenols and ketones commercially available and easily produced but also the halide-containing waste is avoided by using oxygen-based electrophiles. The silylation of unreactive C−O bonds has been carried out by the Martin group, 9 but the formation of alkenylsilanes has been less explored. 9b The transmetalation process of silicon nucleophiles is more sluggish than that of other organometallic reagents. To address this issue, metal-based silicon nucleophiles are always used in crosscoupling reactions. For example, pioneering works were reported by the Oshima and Trost groups, 10 in which the aluminum-based silicon reagents were used (Scheme 1). Very recently, Oestreich and coworkers reported the copper-

Experimental and Computational Studies of the Iron‐Catalyzed Selective and Controllable Defluorosilylation of Unactivated Aliphatic gem‐Difluoroalkenes

“…These results suggest that iron catalysts have some special properties compared with other transition metals.E ncouraged by these results,w e continued our research on the highly selective synthesis of mono-silylated fluoroalkenes.H igher yield and selectivity of mono-silylated fluoroalkene (E)-4a was obtained with lower reaction temperature,( Table 1, entries 11,12). Thel igands were crucial for this reaction, and excellent selectivity and moderate yields could be achieved when dppb was used (Table 1, entries [12][13][14][15]. Furthermore,w hen FeI 2 was used as the catalyst, 80 %y ield of (E)-4a and excellent (Z)/(E)s electivity resulted (Table 1, entry 16).…”

“…Therefore,i ti sh ighly desirable to develop ah ighly efficient and selective catalytic system to access gem-disilylated alkenes and mono-silylated (Z)/(E)-fluoroal-kenes.E ven though the second CÀFb ond cleavage and the silylation of unactivated aliphatic gem-difluoroalkenes are very challenging via transition metal catalysis, [8] we envision that iron catalysis might achieve this novel transformation owing to ironsu npredictable reactivity. [12] Continuing our efforts in organofluorine chemistry [13] and iron catalysis, [14] we set out to develop an efficient method for selective silylation of gem-difluoroalkenes while exploring the unique reactivity of iron catalysis.S uch at ransformation might encounter significant challenges:1 )C À Fb ond cleavage in mono-silylated fluoroalkenes could likely be more sluggish than in difluoroalkenes due to its strong bond dissociation energy, [15,16] as well as the large steric hindrance of the silane group;2 )the stereoselective cleavage of the CÀFb ond is difficult because of the extremely similar energy between the two C À Fbonds.…”

Iron‐Catalyzed Cross‐Coupling Reactions for the Construction of Carbon‐Heteroatom Bonds

“…Very recently, the Feng group developed the first example of iron-catalyzed silylation of aryl and alkenyl carbamates via CÀ O bond activation (Scheme 20). [68] The inert substrates, such as monophenyl or alkenyl carbamates could undergo this transformation smoothly, affording the corresponding products in moderate to good yields. Importantly, this protocol enables the late-stage silyation of biomolecules, thus providing a good platform for the synthesis of multi-substituted arenes using the carbamate group as the directing group.…”

“…In 2016, the Rueping and Shi groups successfully reported the nickel‐catalyzed cross‐coupling of aryl carboxylates with Et 3 Si‐Bpin through the decarboxylation reaction, respectively. Very recently, the Feng group developed the first example of iron‐catalyzed silylation of aryl and alkenyl carbamates via C−O bond activation (Scheme ) . The inert substrates, such as monophenyl or alkenyl carbamates could undergo this transformation smoothly, affording the corresponding products in moderate to good yields.…”

On-Demand Electrochemical Synthesis of copper(I) Triflate and Its Application in the Aerobic Oxidation of Alcohols

“…5,6 Fe II or Fe III triflate salts have performed better than other Fe salts in oxidation, radical addition, and C-O bond silylation. [7][8][9] Despite these representative examples and their widespread use in catalysis, there remain challenges associated with the synthesis of metal triflates, which often involves reacting a metal halide with AgOTf. This can result in water being present in the product, halide impurities and difficult removal of silver salts.…”