Blue‐Light‐Induced Carbene‐Transfer Reactions of Diazoalkanes

Abstract

Carbenes are very important reactive intermediates to access a variety of complex molecules and are applied widely in organic synthesis and drug discovery. Typically, their chemistry is accessed by the use of transition metal catalysts. Herein, we describe the application of low‐energy blue light for the photochemical generation of carbenes from donor–acceptor diazoalkanes. This catalyst‐free and operationally simple approach enables highly efficient cyclopropenation reactions with alkynes and the rearrangement of sulfides under mild reaction conditions, which can be utilized for both batch and continuous‐flow processes.

Stoichiometric Photochemical Carbene Transfer by Bamford–Stevens Reaction

“…In recent years, the visible‐light photolysis of diazoalkanes attracted the interest of organic synthetic chemists to conduct metal‐free carbene‐transfer reactions, and first reports already accentuate its high potential in photochemical, metal‐free cycloaddition, rearrangement, olefination, X−H, and C−H functionalization reactions . Despite these advances, applications are mainly limited to the use of a large excess of one reaction partner due to rapidly occurring side reactions of the carbene intermediate with remaining unreacted diazoalkane molecules, for example, in diazine ( 3 ) formation (Scheme ).…”

Blue Light‐Promoted N−H Insertion of Carbazoles, Pyrazoles and 1,2,3‐Triazoles into Aryldiazoacetates

“…Upon irradiation in the blue/ violet region of the visible spectrum, the photoexcited diazo compound liberates N 2 , thus generating a highly reactive carbene intermediate, which can be trapped with several reacting partners. [4] Examples of cyclopropanations with styrene and arenes; and XÀ H insertions (X=C, N, O) involving carboxylic acids, amines, alkanes and arenes have been reported; [5,6] they have been also reacted with ethyl diazoacetate to afford trisubstituted olefins; [7] underwent cyclopropenation reaction with alkynes; [8] sigmatropic shifts involving sulfur ylides; [8,9] cyclopropenations with hindered propargyl alcohols; [10] or cyclopropanations with indoles. [11] In this context, and as an alternative to metal catalyzed processes, we became also interested in the possibility of developing blue light-promoted NÀ H insertion protocols of carbazoles, pyrazoles and 1,2,3triazoles into aryldiazoacetates.…”

Synthesis of gem‐Difluoro Olefins through C−H Functionalization and β‐fluoride Elimination Reactions

“…A reaction sequence comprising CÀH functionalization and subsequent b-fluoride elimination [14] should enable the direct one-step synthesis of analogues of antitubulin agents (3). Fluorinated diazoalkanes are important reagents for the introduction of trifluoromethyl or difluoromethyl groups into small organic molecules, [15] however applications of this important group of diazoalkanes in C À H functionalization reactions are scarce. Molander and Ryu studied the reaction of 2,2,2-trifluoro diazoethane with indole heterocycles, yet no reaction product was observed.…”