Triorganophosphonium salts are normally air-stable and important reagents in transition metal-catalyzed organic synthesis, which can release air-sensitive triorganophosphines in situ in the presence of bases. Herein, a series of experimentally determined pKa values of P-H bonds of triorganophosphonium salts in toluene are reported. From the self-dissociation equilibrium constant of the anchor compound 2-(4-trifluoromethanesulfonato)phenylmalononitrile which is readily soluble in toluene, the pKa values of P-H bonds in 8 triorganophosphonium bistriflimides and 13 tool compounds (including 10 C-H acids, 2 O-H acids, and one N-H acid in toluene) were experimentally determined based on a combination of UV-visible and 31P{1H} NMR spectroscopic studies. These experimentally determined pKa values exhibit good linear correlations with the corresponding DFT-computationally determined values. In the future, it is expected that these experimentally determined pKa values of P-H bonds in toluene will provide guidelines for the rational design of catalytic reactions.

We developed an electrochemical oxidative oxyalkylation of alkenes with alcohols and 1,3-dicarbonyl compounds to produce diverse 1,3-dicarbonyl modified benzyl ethers in yields of 34-81%. This operationally simple and green process uses an undivided cell with commercial carbon electrodes at room temperature. The alcohol acts as the oxygenation reagent and solvent, and only H2 was generated as a byproduct. The synthetic utility of this method was demonstrated in the rapid synthesis of highly functionalized pyrazole, isoxazole, and 1,4-ketoalcohols compounds through late-stage functional transformations.

An efficient synthesis of spirodihydrobenzofuran derivatives via the 1,4-conjugate addition of iodonium ylides to indene-1,3(2H)-diones, followed by an anomalous Cloke-Wilson rearrangement is reported. This strategy demonstrates a broad substrate scope with a high degree of regioselectivity control. Computational studies involving the natural orbital bond analysis were explored to explain this anomalous formation of unconventional products. In case of alkyne-tethered indenediones, the same regioselectivity control was observed, but in the presence of scandium-triflate in dimethoxyethane (DME), the normal Cloke-Wilson product was observed as an exclusive product.

Platycaryanin A, a structurally complex ellagitannin bearing a rare tergalloyl moiety, has eluded chemical synthesis to date. Herein, we report the first total synthesis of platycaryanin A, addressing key challenges in the regio- and stereoselective construction of its trimeric gallic acid framework. Direct oxidative coupling of galloyl and isodehydrodigalloyl units proved unsuccessful, highlighting the inherent difficulty of regio- and stereoselective assembly. A bioinspired oxa-Michael addition of an isodehydrodigallic acid derivative enabled the efficient formation of the tergalloyl group, followed by strategic functional-group manipulations to deliver platycaryanin A in its natural form. This work establishes a general approach to the synthesis of complex polyphenolic natural products.

Pyrene- and anthracene-stoppered bistable [2]rotaxanes, comprising [23]- and [24]crown ethers, were obtained in high yield by a click reaction. All four [2]rotaxanes exhibited anion-induced shuttling of crown ethers from the ammonium to the methyl triazolium moiety, accompanied by sharp fluorescence enhancements in an acetonitrile/water (v/v = 99:1) medium. The magnitude of fluorescence enhancement, however, has been much greater in the case of shuttling for [23]crown ether (X23C7) than for the [24]crown ether (DB24C8) in both pyrene- and anthracene-stoppered bistable [2]rotaxanes. Anions such as cyanide, fluoride, acetate, and sulfate affected the switching in acetonitrile/water (v/v = 99:1) medium, while only the cyanide anion induced switching in a more hydrated environment, such as acetonitrile/water (v/v = 92:8), where, yet again, greater fluorescence enhancement was observed upon X23C7 shuttling. Reversibility with trifluoroacetic acid was maneuvered toward reproducibility of the fluorescence output and consequent recyclability of these [2]rotaxanes. An impressive nanomolar limit of detection (LOD) for the cyanide anion was observed with all the [2]rotaxanes. Portable cyanide anion investigation with a fixed concentration of anthracene-terminated [2]rotaxanes enabled a naked eye "turn-on" response only when incorporated with the X23C7 macrocycle, thereby manifesting a visually discernible difference with respect to the closely related DB24C8 macrocycle.

Coumarins represent an important class of heterocycles because of their prevalence in nature and their common presence as pharmaceutical structural motifs. However, their synthesis employs harsh conditions or requires a transition metal catalyst, limiting their scalability and sustainability. Herein we report an electrocatalytic synthetic method leading to coumarins using NHC·CS2 (NHC = N-heterocyclic carbene) species as organic mediators. Using this procedure, a variety of substituted coumarins were obtained in good yields, establishing this electrocatalytic strategy as an attractive synthetic alternative. Based on our observations, a reaction mechanism operating through a one-electron reduction and involving a radical intermediate is proposed.

We report a novel, efficient, and highly chemo- and regioselective strategy for the synthesis of O- and C-prenylated resorcinol-based bioactive natural products and their analogues, including derricidin, 4'-O-geranylisoliquirtigenin, sofalcone, derricin, isocordoin, 4-hydroxyderricin, crotaorixin, and xanthoangelol. Vinylogous esters and aldehydes were utilized in a single-pot sequence of aldol reaction, aromatization, and oxidation reactions. Terpene-derived resorcinyl ketones, such as O-prenyl/geranyl and C-prenyl/geranyl derivatives, are widely distributed in nature. However, the direct installation of C-prenyl/geranyl groups onto aromatic rings remains challenging, often requiring protecting groups, multistep sequences, Lewis acids, or high-temperature Claisen rearrangements, which suffer from poor regioselectivity and low yields. For the first time, we demonstrate access to these compounds from nonbenzenoid starting materials such as O- and C-prenylated vinylogous esters. This strategy exploits aldehydes as versatile coupling partners and exhibits excellent tolerance toward these fragile terpene moieties as well as a wide range of sensitive functional groups.

Herein, the concept of biobased vicinal diols as alternative H-bond donors is presented. NMR study revealed superior electrophilic enhancement by ethylene glycol in comparison to other H-bond donors, duly supported by computational studies. As a case study, controlled experiments confirmed the better activation by 1,2-diols over mono-ols, diol regiomers, and other H-bond donors in the Morita-Baylis-Hillman (MBH) reaction. Reaction inhibition with lower conversion in the presence of an acid cocatalyst due to competing protonation of the H-bond acceptor was observed. As a practical application of this concept, a thorough investigation and optimization were carried out to mitigate the sluggishness of sp2-C electrophiles, particularly aliphatic aldehydes, in MBH reactions with various pronucleophiles. The sluggishness of the aliphatic aldehydes with respect to aromatic aldehydes has been assigned to competing amine-trapping zwitterions from side reactions with the electrophiles.

In this study, we report the radical-mediated trifluoromethylation of phenylpropiolamides using the Langlois reagent (CF3SO2Na) under ultraviolet light irradiation, with tetrabutylammonium decatungstate (TBADT) serving as an efficient inorganic photocatalyst. This method synthesizes a wide range of oxindoles by generating a CF3 radical, which induces an intermolecular C-CF3 bond (via a Michael addition on the propiolamide moiety), followed by an intramolecular C-C bond formation and reduction sequence. Thus, a broad range of trifluoromethyl-substituted oxindoles have been accomplished in high yields under mild conditions.

DNA-protein cross-links (DPCs) and DNA-DNA interstrand cross-links (ICLs) strongly block genetic expression. Chemical agents that preferentially produce one of these DNA damage types over the other are potentially useful cellular probes and pharmacological agents but are uncommon. A chimeric alkylating agent (MEBAC) selectively forms DPCs over ICLs by reacting with the ε-amine of lysine. Here we determine that the majority of DPCs formed by MEBAC in NCPs are between dG and lysines in the histone amino terminal tails. We also compare the reactivity of MEBAC and an isomer (m-MEBAC). Model studies indicate that m-MEBAC reacts ∼50% more rapidly than MEBAC with a primary amine. DPC yields in nucleosome core particles (NCPs) from MEBAC and m-MEBAC are approximately equal at all but the highest concentration tested. Comparisons between the reactivity of MEBAC and a nitrogen mustard with NCPs and nuclear lysates illustrate the advantage of the former for generating DPCs. m-MEBAC and MEBAC cytotoxicity in human cells are comparable and are enhanced when proteasomal DPC repair is inhibited. These experiments validate the utility of this family of chimeric bis-electrophiles as chemical tools for forming DPCs in the test tube and in cells.