Fluorinated diazoalkanes – a versatile class of reagents for the synthesis of fluorinated compounds

Abstract

Although diazoalkanes find regular application in organic synthesis, the synthesis and application of their fluorinated homologues was long neglected. First described in 1943, trifluorodiazoethane found its way into the organic synthesis repertoire only in the past decade for atom-economical and practical synthesis of fluorinated building blocks and currently emerges as a versatile reagent. The synthetic applicability of this reagent is currently being investigated in great detail and many interesting new reactivities, and procedures for the synthesis of fluoroalkyl-substituted building blocks have been developed. In this context, a range of new fluoroalkyl substituted diazoalkanes have been introduced in the past few years, ranging from perfluorinated diazoalkanes towards highly reactive difluorodiazoethane which was first described in 2015. This tutorial review covers historic milestones of fluoroalkyl substituted diazoalkanes and highlights recent examples which underscore their vast potential to the synthesis of fluorinated compounds.

Telescoping Reactions with Trifluorodiazoethane‐Derived Aza‐Wittig Reagents and Allenyl esters

“…For the purpose of generating molecular diversity from allenyl esters, we oriented our research to uncover new reactionp roducts with phosphazenes (aza-Wittig reagents) derived from trifluorodiazoethane (CF 3 CHN 2 ). [8] We envisioned that thesen ovel phosphazenes would react with allenyle sters in af ormal [3+ +2] cycloaddition to provide new trifluoromethylated 3H-pyrazoles, with unprecedented patterns,a nd further aromatic 1H-pyrazoles throught hermal [1,5]-sigmatropic rearrangement( Scheme 1a). [9][10][11][12] We thought it would be effective, but we weres urprised to obtain at otally different reaction product, which was identified as an iminophosphorane (Scheme 1b).…”

Substrate‐Controlled Cyclopropanation Reactions of Glycals with Aryl Diazoacetates

“…Based on our research interest in fluorinated diazoalkanes, [14,15] we next studied fluorinated donor acceptor diazoalkanes 9 a-c (Scheme 2b). Under otherwise identical conditions, the desired fluorinated cyclopropanes 10 a-c could be isolated in moderate to very good yields, now showcasing the first examples of cyclopropanation reactions of d-glucal with fluorinated diazoalkanes.…”

The Generation of Diazo Compounds in Continuous‐Flow

“…In a second, organic stream different aldehydes were added into the tube‐in‐tube reactor. Trifluorodiazoethane ( 40 ), generated in flow can diffuse through the AF‐2400 membrane and reacts with aldehydes to give the addition products, which, after passing through a cartridge of polymer‐supported DBU yields the desired diazo compounds ( 45 ) in moderate to good yields. It should be mentioned that trifluoro diazoethane was obtained in 33 % yield using this protocol.…”

“…In 2016, Koenigs and co‐workers described this concept using flow chemistry protocols . In this context, difluoro diazoethane ( 50 a ) proved to be a particularly useful reagent for flow protocols as it readily decomposes under aqueous conditions and suffers from low stability ,. In a first report, Koenigs et al.…”