Nucleophilic transformations of azido-containing carbonyl compounds via protection of the azido group.

Nucleophilic transformations of azido-containing carbonyl compounds are discussed. The phosphazide formation from azides and di(tert-butyl)(4-(dimethylamino)phenyl)phosphine (Amphos) enabled transformations of carbonyl groups with nucleophiles such as lithium aluminum hydride and organometallic reagents. The good stability of the phosphazide moiety allowed us to perform consecutive transformations of a diazide through triazole formation and the Grignard reaction.

Triazole formation of phosphinyl alkynes with azides through transient protection of phosphine by copper.

An efficient preparation method of functionalized phosphines by copper-catalyzed azide-alkyne cycloaddition (CuAAC) through the transient protection of phosphine from the Staudinger reaction is disclosed. Diverse phosphines were prepared from phosphinyl alkynes and azides by the click reaction at the ethynyl group without damaging the phosphinyl group. Double- and triple-click assemblies of azides were accomplished by triazole formations and robust azaylide formation.

(Hexafluoroacetylacetonato)copper(I)-cycloalkyne complexes as protected cycloalkynes.

A protection method for cycloalkynes by the formation of (hexafluoroacetylacetonato)copper(i)-cycloalkyne complexes is disclosed. Various complexes having functional groups were efficiently prepared, which are easily purified by silica-gel column chromatography. Selective click reactions were realized through the complexation of cycloalkynes with copper.

Selective strain-promoted azide-alkyne cycloadditions through transient protection of bicyclo[6.1.0]nonynes with silver or gold.

Complexation of bicyclo[6.1.0]nonynes with a cationic silver or gold salt results in protection from a click reaction with azides. The cycloalkyne protection using the silver or gold salt enables selective strain-promoted azide-alkyne cycloadditions of diynes keeping the bicyclo[6.1.0]nonyne moiety unreacted.

Facile assembly of three cycloalkyne-modules onto a platform compound bearing thiophene S,S-dioxide moiety and two azido groups.

An efficient method to assemble three cycloalkyne-modules onto a platform compound bearing a thiophene S,S-dioxide moiety and two azido groups has been developed. The sequential reactions without catalysis or additives enabled the facile preparation of trifunctional molecules by a simple procedure. One-pot assembly was also achieved using the platform and three cycloalkynes.

A facile preparation of functional cycloalkynes via an azide-to-cycloalkyne switching approach.

A facile method for preparing various functional cycloalkynes, including proteins incorporated with a cycloalkyne moiety, from the corresponding azides is developed. Treatment of diynes bearing strained and terminal alkyne moieties with a copper salt enabled terminal alkyne-selective click conjugation with azides, whereas a more azidophilic strained alkyne moiety was transiently protected from the click reaction via complexation with copper.

Transient Protection of Organic Azides from Click Reactions with Alkynes by Phosphazide Formation.

A method for protecting organic azides from click reactions with alkynes is reported. Treatment of azides with Amphos affords phosphazides, which are stable under click reaction conditions and are easily converted back to azides by treatment with elemental sulfur. Thus, the method allows for facile modification of azide compounds via site-selective click reactions.

Staudinger reaction using 2,6-dichlorophenyl azide derivatives for robust aza-ylide formation applicable to bioconjugation in living cells.

Efficient formation of water- and air-stable aza-ylides has been achieved using the Staudinger reaction between electron-deficient aromatic azides such as 2,6-dichlorophenyl azide and triarylphosphines. The reaction proceeds rapidly and has been successfully applied to chemical modification of proteins in living cells.