Designs and Strategies for the Halo‐Functionalization of Diazo Compounds

Abstract

Organo halides and their derivatives have received much attention in both the design and development of new synthetic reagents, drugs, and functional materials. In this review, we provide a comprehensive summary of recent advances and strategies in the halo‐functionalization of diazo compounds, including halogenation, dihalogenation, dihaloolefination, trifluoromethylation, trifluoromethylthiolation, and trifluoromethoxylation, using diverse halogenating agents. Special emphasis is placed on the challenges and achievements of these halogenation strategies. For selected examples, mechanisms leading to unusual reactivities and selectivities are discussed in detail to show the impressive and unique properties of these halogenation reactions. Furthermore, we hope to encourage the scientific community to explore the benefits of using diazo compounds as a straightforward and step‐economic alternative approach to the construction of carbon‐halogen bonds.

Emerging Applications of Aryl Trifluoromethyl Diazoalkanes and Diazirines in Synthetic Transformations

“…The addition of fluoride and fluoroalkyl-derived groups to aryl trifluoromethyl diazo compounds is an great example for the formation of various fluorinated alkanes ( Scheme 32 ). 84 − 86 The efficient trifluoromethylthiolation of diazo compounds through copper-carbene migratory insertion was reported by Wang et al 85 Gouverneur et al. notably demonstrated the versatility of the use of these diazo compounds, obtaining excellent yields on a wide range of compounds.…”

Metal-free aminofluorination of α-diazo 2H-benzopyran-4-one: convenient access to β-fluoramides

“…To date, significant advances have been achieved toward the reaction of diazoalkanes with fluorinating agents that allows introducing a fluorine atom together with other functional groups of the carbene intermediate. 3 a ,6 In this context, Szabó and co-workers reported the reaction of diazocarbonyl compounds with the fluoro-benziodoxole reagent and various alcohols for the important oxyfluorination of carbonyl compounds using a Rh( ii ) catalyst (Scheme 1b). 3 c The Doyle group disclosed the enantioselective monofluorination reaction of aryldiazoketones in the presence of a chiral Cu( i ) catalyst.…”

The Versatile Reaction Chemistry of an Alpha-Boryl Diazo Compound

“…Importantly, the annulation method involving potassium chloromethyltrifluoroborate and 2-aminostyrene to yield the chloromethyl BN naphthalenes is not applicable to the monocyclic benzene-type BN heterocycle. We envisioned that similar to how O -alkylation proceeds with protonation of the α-boryl carbon followed by nucleophilic attack of the oxygen nucleophile, treatment of 1 with a suitably matched proton/halide source should yield the corresponding halomethyl 1,2-azaborines 9 and 10 . After screening a number of conditions, we determined that 1-ethynyl-4-nitrobenzene as the proton source in combination with CuI as the iodide nucleophile works well for the iodination of diazomethyl-1,2-azaborine 1 (Scheme , eq 8).…”