Regioselective C-H Xanthylation as a Platform for Polyolefin Functionalization.

Polyolefins that contain polar functional groups are important materials for next-generation lightweight engineering thermoplastics. Post-polymerization modification is an ideal method for the incorporation of polar groups into branched polyolefins; however, it typically results in chain scission events, which have deleterious effects on polymer properties. Herein, we report a metal-free method for radical-mediated C-H xanthylation that results in the regioselective functionalization of branched polyolefins without coincident polymer-chain scission. This method enables a tunable degree of polymer functionalization and capitalizes on the versatility of the xanthate functional group to unlock a wide variety of C-H transformations previously inaccessible on branched polyolefins.

A General Strategy for Aliphatic C-H Functionalization Enabled by Organic Photoredox Catalysis.

Synthetic transformations that functionalize unactivated aliphatic C-H bonds in an intermolecular fashion offer unique strategies for the synthesis and late-stage derivatization of complex molecules. Herein we report a general approach to the intermolecular functionalization of aliphatic C-H bonds using an acridinium photoredox catalyst and phosphate salt under blue LED irradiation. This strategy encompasses a range of valuable C-H transformations, including the direct conversions of a C-H bond to C-N, C-F, C-Br, C-Cl, C-S, and C-C bonds, in all cases using the alkane substrate as the limiting reagent. Detailed mechanistic studies are consistent with the intermediacy of a putative oxygen-centered radical as the hydrogen atom-abstracting species in these processes.

Tuning the pKa of Fluorescent Rhodamine pH Probes through Substituent Effects.

Rhodamine spirolactams (RSLs) have recently emerged as popular fluorescent pH probes due to their fluorescence turn-on capability and ease of functionalization at the spirolactam nitrogen. Design of RSLs is often driven by biological targeting or compatibility concerns, rather than the pH sensitivity of the probe, and the relationship between RSL structure and pKa is not well understood. To elucidate the relationship between pKa values and the properties of substituents attached to the spirolactam nitrogen, a series of 19 aniline-derived RSLs is presented. RSLs derived from di-ortho-substituted anilines exhibit pKa tunability across the moderately acidic region (ca. pH 4-6). Evaluation of pKa data using the Fujita-Nishioka model for ortho substituent effects reveals that both steric and electronic substituent properties influence RSL pH responsiveness, with pKa values increasing as substituent size and electron withdrawing character increase. These trends are attributed to changes in the RSL structure induced by large substituents, and to electronic influences on the protonated spirocyclic reaction intermediate. To demonstrate the practical applicability of these probes in completely aqueous environments, RSL-doped conjugated polymer nanoparticles that exhibit a ratiometric fluorescence response to changing pH levels are presented.

A General Approach to Quaternary Center Construction from Couplings of Unactivated Alkenes and Acyl Xanthates.

A general, radical-mediated approach to quaternary center construction using unactivated alkenes as coupling partners is reported. In this strategy, acyl xanthates, readily accessed from carboxylic acids, serve as precursors to tertiary radicals. This strategy leverages the unique reactivity of xanthates to participate in efficient radical-mediated additions to unactivated alkenes, expanding the scope of quaternary center construction.

C-H Xanthylation: A Synthetic Platform for Alkane Functionalization.

Intermolecular functionalizations of aliphatic C-H bonds offer unique strategies for the synthesis and late-stage derivatization of complex molecules, but the chemical space accessible remains limited. Herein, we report a transformation significantly expanding the chemotypes accessible via C-H functionalization. The C-H xanthylation proceeds in useful chemical yields with the substrate as the limiting reagent using blue LEDs and an easily prepared N-xanthylamide. The late-stage functionalizations of complex molecules occur with high levels of site selectivity, and a variety of common functionality is tolerated in the reaction. This approach capitalizes on the versatility of the xanthate functional group via both polar and radical manifolds to unlock a wide array of C-H transformations previously inaccessible in synthesis.

Substituent effects on the turn-on kinetics of rhodamine-based fluorescent pH probes.

Fluorescent turn-on probes based on a rhodamine spirolactam (RSL) structure have recently become a popular means of detecting pH, metal ions, and other analytes of interest. RSLs are colorless and non-fluorescent until the target analyte induces opening of the spirocyclic ring system, revealing the fully conjugated and highly fluorescent rhodamine dye. Among RSLs opened by acid, we have observed wide variation in the kinetics of the fluorescence turn-on process such that some probes would not be usable in situations where a rapid reading is desired or the pH fluctuates temporally. Herein we present a systematic investigation of the fluorescence turn-on kinetics of RSLs to probe the hypothesis that the reaction rates are influenced by the electronic properties of the spirolactam ring system. A series of 8 aniline-derived RSLs with para substituents ranging from electron-donating to electron-withdrawing was prepared from rhodamine B. The fluorescence turn-on rates are observed to increase by a factor of four as the substituent is tuned from methoxy to nitro. This effect is explained in terms of the destabilization of the reaction intermediate by the substituent. As the reaction rates increase across the series, a concomitant increase in fluorescence intensity is also observed. This result is attributed to an increase in the concentration of the fluorescent form of the dye and is consistent with the expected equilibrium properties of this system. These findings are applied to the design of a faster-reacting and more intensely fluorescent RSL pH probe.