Dehydrogenative Transformations of Imines Using a Heterogeneous Photocatalyst.

Heterogeneous semiconductors are underexploited as photoredox catalysts in organic synthesis relative to their homogeneous, molecular counterparts. Here, we report the use of metal/TiO particles as catalysts for light-induced dehydrogenative imine transformations. The highly oxophilic nature of the TiO surface promotes the selective binding and dehydrogenation of alcohols in the presence of other oxidizable and Lewis basic functional groups.

Rh(II)-Catalyzed Reactions of Diazoesters with Organozinc Reagents.

Rh(II)-catalyzed reactions of diazoesters with organozinc reagents are described. Diorganozinc reagents participate in reactions with diazo compounds by two distinct, catalyst-dependent mechanisms. With bulky diisopropylethyl acetate ligands, the reaction mechanism is proposed to involve initial formation of a Rh-carbene and subsequent carbozincation to give a zinc enolate.

Improved metabolic stability for 18F PET probes rapidly constructed via tetrazine trans-cyclooctene ligation.

The fast kinetics and bioorthogonal nature of the tetrazine trans-cyclooctene (TCO) ligation makes it a unique tool for PET probe construction. In this study, we report the development of an (18)F-labeling system based on a CF3-substituted diphenyl-s-tetrazine derivative with the aim of maintaining high reactivity while increasing in vivo stability. c(RGDyK) was tagged by a CF3-substituted diphenyl-s-tetrazine derivative via EDC-mediated coupling.

An efficient and mild oxidant for the synthesis of -tetrazines.

PhI(OAc) serves as a mild and effective oxidant for the synthesis of -tetrazine derivatives- molecules of emerging significance to the field of bioorthogonal chemistry. This reagent serves as a complementary oxidant to harsher nitrous reagents. Use of PhI(OAc) improves the synthesis of 5-amino-di(pyridin-2-yl)-s-tetrazine, a molecule that has been broadly used for cellular imaging and nuclear medicine.

trans-Cyclooctene--a stable, voracious dienophile for bioorthogonal labeling.

Discussed herein is the development and advancement of trans-cyclooctene as a tool for facilitating bioorthogonal labeling through reactions with s-tetrazines. While a number of strained alkenes have been shown to combine with tetrazines for applications in bioorthogonal labeling, trans-cyclooctene enables fastest reactivity at low concentration with rate constants in excess of k2=10(6) M(-1) s(-1). In the present article, we describe advances in computation and synthesis that have enabled applications in chemical biology and nuclear medicine.

Efficient 18F labeling of cysteine-containing peptides and proteins using tetrazine-trans-cyclooctene ligation.

18F positron emission tomography (PET) has a number of attributes that make it clinically attractive, including nearly 100% positron efficiency, very high specific radioactivity, and a short half-life of ≈ 110 minutes. However, the short half-life of 18F and the poor nucleophilicity of fluoride introduce challenges for the incorporation of 18F into complex molecules. Recently, the tetrazine-trans-cyclooctene ligation was introduced as a novel 18F labeling method that proceeds with fast reaction rates without catalysis.

Facially selective Cu-catalyzed carbozincation of cyclopropenes using arylzinc reagents formed by sequential I/Mg/Zn exchange.

Described is a Cu-catalyzed directed carbozincation of cyclopropenes with organozinc reagents prepared by I/Mg/Zn exchange. This protocol broadens the scope with respect to functional group tolerance and enables use of aryl iodide precursors, rather than purified diorganozinc precursors. Critical to diastereoselectivity of the carbozincation step is the removal of magnesium halide salts after transmetalation with ZnCl(2).

Diels-Alder cycloaddition for fluorophore targeting to specific proteins inside living cells.

The inverse-electron-demand Diels-Alder cycloaddition between trans-cyclooctenes and tetrazines is biocompatible and exceptionally fast. We utilized this chemistry for site-specific fluorescence labeling of proteins on the cell surface and inside living mammalian cells by a two-step protocol. Escherichia coli lipoic acid ligase site-specifically ligates a trans-cyclooctene derivative onto a protein of interest in the first step, followed by chemoselective derivatization with a tetrazine-fluorophore conjugate in the second step.

Tetrazine-trans-cyclooctene ligation for the rapid construction of integrin αvβ₃ targeted PET tracer based on a cyclic RGD peptide.

Labeling biomolecules with (18)F is usually done through coupling with prosthetic groups, which generally requires several time-consuming radiosynthetic steps resulting in low labeling yield. Recently, the tetrazine-trans-cyclooctene ligation has been introduced as a method of bioconjugation that proceeds with fast reaction rates without need for catalysis. Herein, we report the development of an extremely fast and efficient method for generating (18)F labeled probes based on the tetrazine-trans-cyclooctene ligation.