Iron‐Catalysed Carbene Transfer to Isocyanides as a Platform for Heterocycle Synthesis

Abstract

An iron-catalysed carbene transfer reaction of diazo compounds to isocyanides has been developed. The resulting ketenimines are trapped in situ with various bisnucleophiles to access a range of densely functionalized heterocycles (pyrimidinones, dihydropyrazolones, 1H-tetrazoles) in a onepot process. The electron-rich Hieber anion ([Fe(CO) 3 NO] À ) facilitates efficient catalytic carbene transfer from acceptortype α-diazo carbonyl compounds to isocyanides, providing a cost-efficient and benign alternative to similar noble metalcatalysed processes. Based on DFT calculations a plausible reaction mechanism for activation of the α-diazo carbonyl carbene precursor and ketenimine formation is provided.

Dearomative Spirocyclization of Tryptamine-Derived Isocyanides via Iron-Catalyzed Carbene Transfer

“…In contrast, in the analogous Pd-catalyzed reaction, these carbenes were converted to indolenines 23aa and 23ba in good to excellent yield . A similar limitation in scope of α-diazo esters was observed in the recently reported iron-catalyzed intermolecular carbene transfer to isocyanides, where we used amidines to trap the ketenimine intermediate . Next, we employed diethyl 2-diazosuccinate ( 18b ) of the acceptor-type carbene class, which was reacted with isocyanides 1a and 1b to give the corresponding spiroindolenines 23ab and 23bb in moderate yield.…”

“…Shifting from Pd-catalyzed processes to base metals, such as iron, is highly desired, due to their high abundancy on Earth and low cost. Recently, our group developed an iron-catalyzed carbene transfer reaction to isocyanides for the construction of multiple heterocycles . The ferrate complex, Bu 4 N­[Fe­(CO) 3 NO] (also known as the Hieber anion), was demonstrated to effectively catalyze the transfer of carbenes to isocyanides to give a ketenimine intermediate.…”

Green and effective synthesis of multisubstituted α-pyrones via K2CO3 catalyzed formal insertion of ketenimines into C(CO)–C bonds of 1,3-diketones

“…Ketenimines could be easily prepared from isocyanides and α-diazo esters according to our previous work. 18 To simplify the operation for accessing α-pyrones, we therefore attempt to merge the Pd-catalyzed cross-coupling reaction and K 2 CO 3 -catalyzed Mannich/lactonization/acyl transfer reaction into a one-pot sequential protocol. Since CH 3 CN was the suitable solvent for both cross-coupling and Mannich/lactonization/acyl transfer reaction, a facile one-pot cascade sequence was developed.…”

“…We have recently developed an efficient protocol to construct polycyclic spiroindolines by a tandem cross-coupling/spirocyclization/Mannich-type reaction of tryptamine-derived isocyanides with α-diazo esters (Scheme 1b). 17 However, attempts to isolate the reactive ketenimine 18 intermediate Int-I of this transformation proved to be difficult because of its facile consumption through further intramolecular spirocyclization reaction to generate tricyclic spiroindolenine Int-II . More recently, we 19 and Bi 20 have successively discovered that the replacement of indole group with a less electron-rich aromatic ring could make the resulting ketenimines chromatography-stable and directly isolable.…”

Recent Advances in Non-Precious Metal Catalysis

“…Iron-catalyzed carbene transfer reaction for accessing isocyanides was developed by Orru and colleagues (Scheme ). A nucleophilic, low-valent iron complex Bu 4 N­[Fe­(CO) 3 NO], also known as the Hieber anion, was found to be a suitable catalyst for carbene transfer from diazo compounds to isocyanides. The resulting ketenimine intermediates could be used directly in situ with nitrogen-containing nucleophiles in a one-pot procedure.…”