This work delineates a method for the modular synthesis of reagents that are capable of direct incorporation of difluoroalkyl groups onto heterocycles. The scope and generality of this method is exemplified with the difluoroethyl group (along with the introduction of a new reagent for difluoroethylation, DFES-Na) and a proof of principle is shown for a general synthesis of fluorinated heteroarylether bioisosteres.

Signal amplification techniques are broadly used to improve the detection sensitivity of various analytes for diagnostic purposes. We have developed a novel, non-PCR-based modular technique for exponential amplification of diagnostic signals that is conveniently performed in an aqueous environment. The technique is based on a distinctive dendritic chain reaction (DCR); the diagnostic signal is generated upon disassembly of a self-immolative dendrimer that releases chromogenic molecules. Under ideal conditions, a single analyte molecule initiates a DCR that generates a strong diagnostic signal. When coupled with a protease diagnostic probe, the DCR technique detected the activity of penicillin-G-amidase with high sensitivity. This is the first example of exponential signal amplification performed under aqueous conditions that is not based on PCR.

A simple method for direct C–H imidation is reported using a new perester-based self-immolating reagent and a base-metal catalyst. The succinimide products obtained can be easily deprotected in situ (if desired) to reveal the corresponding anilines directly. The scope of the reaction is broad, the conditions are extremely mild, and the reaction is tolerant of oxidizable and acid-labile functionality, multiple heteroatoms, and aryl iodides. Mechanistic studies indicate that ferrocene (Cp2Fe) plays the role of an electron shuttle in the decomposition of the perester reagent, delivering a succinimidyl radical ready to add to an aromatic system.

A new self-immolative dendritic probe directly detects triacetone triperoxide through amplification of a single cleavage event initiated by one molecule of hydrogen peroxide into multiple-release of fluorogenic end-groups.

New analytical diagnostic techniques that are based on signal-amplification mechanisms could significantly improve the sensitivity of detection of various analytes. We have developed a new approach to achieving exponential amplification of a diagnostic signal through a two-component dendritic chain reaction. The chain reaction generated the analyte of interest and thereby initiated additional diagnostic cycles. The system was designed for the detection of hydrogen peroxide and produced significantly larger intensity of diagnostic signal than a classic probe. In addition, a mathematical model that simulates the disassembly kinetics of one-component and two-component reactions was developed and shown to correlate well with the observed experimental data. The modularity and flexibility of a two-component detection system should allow extension to the detection of other analytes.