Aliphatic azides are a versatile
class of compounds found in a
variety of biologically active pharmaceuticals. These compounds are
also recognized as useful precursors for the synthesis of a range
of nitrogen-based scaffolds of therapeutic drugs, biologically active
compounds, and functional materials. In light of the growing importance
of aliphatic azides in both chemical and biological sciences, a vast
array of synthetic strategies for the preparation of structurally
diverse aliphatic azides have been developed over the past decades.
However, to date, this topic has not been the subject of a dedicated
review. This review aims to provide a concise overview of modern synthetic
strategies to access aliphatic azides that have emerged since 2010.
The discussed azidation reactions include (a) azidation of C–C
multiple bonds, (b) azidation of C–H bonds, (c) the direct
transformation of vinyl azides into other aliphatic azides, and (d)
miscellaneous reactions to access aliphatic azides. We critically
discuss the synthetic outcomes and the generality and uniqueness of
the different mechanistic rationale of each of the selected reactions.
The challenges and potential opportunities of the topic are outlined.
A silver‐catalyzed intermolecular aminosulfonylation of terminal alkynes with sodium sulfinates and TMSN3 is reported. This three‐component reaction proceeds through sequential hydroazidation of the terminal alkyne and addition of a sulfonyl radical to the resultant vinyl azide. The method enables the stereoselective synthesis of a wide range of β‐sulfonyl enamines without electron‐withdrawing groups on the nitrogen atom. These enamines are found to be suitable for a variety of further transformations.
A copper(I)-catalyzed, regioselective C-H α-trifluoromethylation of α,β-unsaturated carbonyl compounds using Togni's reagent was developed. Diverse substrates, including enones as well as α,β-unsaturated esters, thioesters, and amides, stereospecifically afforded the corresponding (E)-α-trifluoromethylated products in moderate to high yields. Further, this method was applied to the C-H trifluoromethylation of drugs.
An electron-withdrawing-group-generable radical-induced enamination of vinyl azides is reported, which results in a variety of β-functionalized N-unprotected enamines in a stereoselective manner. A plausible mechanism involving an unusual 1,3-H transfer of in situ generated iminyl radical intermediate was proposed on the basis of experimental results and DFT calculations.
An unprecedented 1,2-azide migration has been developed through gemdifluorination of the easily available a-vinyl azides with in situ-generated PhIF 2 ,HF. This approach provides a platform for the downstream synthesis of b-difluorinated alkyl azides in high yields with broad substrate scope and excellent functional group tolerance. The DFT calculations suggest 1,2-azide migration occur via a three-membered azacyclic transition state.
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