Rapid Biomolecular Trifluoromethylation Using Cationic Aromatic Sulfonate Esters as Visible-Light-Triggered Radical Photocages

Described here is a photodecaging approach to radical trifluoromethylation of biomolecules. This was accomplished by designing a quinolinium sulfonate ester that, upon absorption of visible light, achieves decaging via photolysis of the sulfonate ester to ultimately liberate free trifluoromethyl radicals that are trapped by π-nucleophiles in biomolecules. This photodecaging process enables protein and protein-interaction mapping experiments using trifluoromethyl radicals that require only 1 s reaction times and low photocage concentrations. In these experiments, aromatic side chains are labeled in an environmentally dependent fashion, with selectivity observed for tryptophan (Trp), followed by histidine (His) and tyrosine (Tyr). Scalable peptide trifluoromethylation through photodecaging is also demonstrated, where bespoke peptides harboring trifluoromethyl groups at tryptophan residues can be synthesized with 5–7 min reaction times and good yields

Enantioselective Synthesis of Cyclobutanes via Sequential Rh-catalyzed Bicyclobutanation/Cu-catalyzed Homoconjugate Addition

Enantiomerically enriched cyclobutanes are constructed by a three-component process in which <i>t</i>-butyl (<i>E</i>)-2-diazo-5-arylpent-4-enoates are treated with Rh₂(<i>S</i>-NTTL)₄ to provide enantiomerically enriched bicyclobutanes, which can subsequently engage in homoconjugate addition/enolate trapping sequence to give densely functionalized cyclobutanes with high diastereoselectivity. This three-component, two-catalyst procedure can be carried out in a single flask. Rh₂(<i>S</i>-NTTL)₄-catalyzed reaction of <i>t</i>-butyl (<i>Z</i>)-2-diazo-5-phenylpent-4-enoate gives the Büchner cyclization product in excellent enantioselectivity

Enantioselective Synthesis of Cyclobutanes via Sequential Rh-catalyzed Bicyclobutanation/Cu-catalyzed Homoconjugate Addition

Enantiomerically enriched cyclobutanes are constructed by a three-component process in which <i>t</i>-butyl (<i>E</i>)-2-diazo-5-arylpent-4-enoates are treated with Rh₂(<i>S</i>-NTTL)₄ to provide enantiomerically enriched bicyclobutanes, which can subsequently engage in homoconjugate addition/enolate trapping sequence to give densely functionalized cyclobutanes with high diastereoselectivity. This three-component, two-catalyst procedure can be carried out in a single flask. Rh₂(<i>S</i>-NTTL)₄-catalyzed reaction of <i>t</i>-butyl (<i>Z</i>)-2-diazo-5-phenylpent-4-enoate gives the Büchner cyclization product in excellent enantioselectivity

Enantioselective Synthesis of Cyclobutanes via Sequential Rh-catalyzed Bicyclobutanation/Cu-catalyzed Homoconjugate Addition

Enantiomerically enriched cyclobutanes are constructed by a three-component process in which <i>t</i>-butyl (<i>E</i>)-2-diazo-5-arylpent-4-enoates are treated with Rh₂(<i>S</i>-NTTL)₄ to provide enantiomerically enriched bicyclobutanes, which can subsequently engage in homoconjugate addition/enolate trapping sequence to give densely functionalized cyclobutanes with high diastereoselectivity. This three-component, two-catalyst procedure can be carried out in a single flask. Rh₂(<i>S</i>-NTTL)₄-catalyzed reaction of <i>t</i>-butyl (<i>Z</i>)-2-diazo-5-phenylpent-4-enoate gives the Büchner cyclization product in excellent enantioselectivity

Genetically Encoded Tetrazine Amino Acid Directs Rapid Site-Specific <i>in Vivo</i> Bioorthogonal Ligation with <i>trans</i>-Cyclooctenes

Bioorthogonal ligation methods with improved reaction rates and less obtrusive components are needed for site-specifically labeling proteins without catalysts. Currently no general method exists for <i>in vivo</i> site-specific labeling of proteins that combines fast reaction rate with stable, nontoxic, and chemoselective reagents. To overcome these limitations, we have developed a tetrazine-containing amino acid, <b>1</b>, that is stable inside living cells. We have site-specifically genetically encoded this unique amino acid in response to an amber codon allowing a single <b>1</b> to be placed at any location in a protein. We have demonstrated that protein containing <b>1</b> can be ligated to a conformationally strained <i>trans</i>-cyclooctene <i>in vitro</i> and <i>in vivo</i> with reaction rates significantly faster than most commonly used labeling methods