Assembly of four modules onto a tetraazide platform by consecutive 1,2,3-triazole formations.

Efficient consecutive 1,2,3-triazole formations using multiazide platforms are disclosed. On the basis of unique clickability of the 1-adamantyl azido group, a four-step synthesis of tetrakis(triazole)s was achieved from a tetraazide platform molecule. This method was applied to a convergent synthesis of tetrafunctionalized probes in a modular synthetic manner.

Synthesis of Diverse Aromatic Ketones through C-F Cleavage of Trifluoromethyl Group.

An efficient synthetic method of aromatic ketones through C-F cleavage of trifluoromethyl group is disclosed. The high functional group tolerance of the transformation and the remarkable stability of trifluoromethyl group in various reactions enabled multi-substituted aromatic ketone synthesis in an efficient route involving useful transformations such as ortho-lithiation, aryne chemistry, and cross-couplings.

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.

Expanding the synthesizable multisubstituted benzo[b]thiophenes via 6,7-thienobenzynes generated from o-silylaryl triflate-type precursors.

Various 2,3-disubstituted 6,7-thienobenzynes have been efficiently generated from the corresponding o-silylaryl triflate-type precursors by activation with fluoride ions. The method has expanded the scope of synthesizable multisubstituted benzothiophenes, including those with various heteroatom substituents, and can be applied to the synthesis of EP4 antagonist analogs.

Substituted 5,6,11,12-tetradehydrodibenzo[a,e]cyclooctenes: syntheses, properties, and DFT studies of substituted Sondheimer-Wong diynes.

Highly strained cyclic acetylenes 5,6,11,12-tetradehydrodibenzo[a,e]cyclooctenes (Sondheimer-Wong diynes) having various substituents on their benzene rings were synthesized successfully by one-pot treatment of the corresponding formyl sulfones with diethyl chlorophosphate/lithium hexamethyldisilazide (LiHMDS) and then lithium diisopropylamide (LDA). When mixtures of two types of formyl sulfones bearing different substituents were subjected to this protocol, the unsymmetrically substituted Sondheimer-Wong diynes could be synthesized in a stepwise manner by isolation of the heterocoupled vinyl sulfone intermediates followed by their treatment with LDA. The UV-vis absorption spectra and cyclic voltammograms of the substituted Sondheimer-Wong diynes were recorded. The electronic effect of substituents on the diynes was investigated in their click reactions and nucleophilic and electrophilic additions.

Modular synthesis of bis- and tris-1,2,3-triazoles by permutable sequential azide-aryne and azide-alkyne cycloadditions.

A modular synthetic method for bis- and tris-1,2,3-triazoles that include a benzotriazole structure was developed on the basis of sequential azide-aryne and azide-alkyne cycloadditions. The key to success was efficient halogen-metal exchange reaction-mediated generation of aryne from ortho-iodoaryl triflates bearing a base-sensitive terminal alkyne moiety, which was achieved using trimethylsilylmethyl Grignard reagent.