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Redox-neutral carbon–carbon (C–C) bond activation and functionalization strategies of cyclopropanols that give metallo homoenolate have offered merits to construct a range of useful β-functionalized ketones in an inverse-polarity fashion. Discovery and identification of oxidative C–C activation reactions of cyclopropanols that generate metallo enolate–homoenolate would provide an opportunity to afford α,β-difunctionalized ketones. We report catalytic, net oxidative C–C activation, and silylation of cyclopropanols with traceless acetal directing groups under consecutive Ir and Rh catalysis in regio-, stereo-, and chemo-selective fashion. In detail, Ir-catalyzed hydrosilylation of cyclopropyl acetates provides the acetal directing group in quantitative yield. Rh-catalyzed proximal C–C silylation of the resulting cyclopropyl silyl acetal produces the metallo enolate–homoenolate equivalent, dioxasilepine, which uniquely holds an interconnected β-silyl moiety and Z-vinyl acetal. Upon sequential treatment of a silaphile that removes the acetal directing group and electrophile, the seven-membered silicon-containing heterocycle, serving as the ketone α,β-dianion equivalent, delivers α,β-difunctionalized ketones. Scope of the hitherto unexplored reactivity of cyclopropanols toward net oxidative C–C silylation and the versatility of the resulting dioxasilepines were demonstrated. These include late-stage, net oxidative C–C silylation of biologically relevant molecules and facile production of a range of α,β-difunctionalized ketones. Preliminary mechanistic studies suggest that the C–C activation harnessing the electron-rich Wilkinson-type catalyst is likely the turnover-determining step and a Rh-π interaction is the key to the efficient metal insertion to the proximal C–C bond in cyclopropanols.

The frequent occurrence of per- and polyfluoroalkyl substances (PFAS) in the water environment is a recent global concern. Because of their extraordinarily strong chemical stability caused by the m...

A triazine ring derivatized with morpholine, an N-alkyl-N'-BOC-hydrazine (alkyl=isopropyl or benzyl) and the diethylacetal of glycinylpropionaldehyde undergoes spontaneous dimerization in good yields upon acid-catalyzed deprotection. The resulting 24-member macrocycles can be characterized by NMR spectroscopy, mass spectrometry, and single crystal X-ray diffraction. In the solid state, both homodimers adopt a taco-like conformation. Although each shows π-π stacking between the triazine rings, different patterns of hydrogen bonds emerge. The crystal structure of the isopropyl dimer shows that it includes two molecules of trifluoracetic acid per macrocycle. The trifluoroacetate anion charge balances the protonated triazines, which engage in bifurcated hydrogen bonds with the carbonyl acceptor of the distant glycine. This carbonyl also forms a hydrogen bond with the NH of the proximate glycine. The crystal structure of the benzyl derivative does not include trifluoracetic acid. Instead, two hydrogen bonds form, each between a glycine NH and the lone pair of the C=N nitrogen of the hydrazine group. In the solid state, both molecules present the alkyl side chains and morpholine groups in close proximity. A heterodimer is accessible in approximately statistical yields-along with both homodimers-by mixing the two protected monomers prior to subjecting them to deprotection.

Organosilanes are used in a broad range of industrial, cosmetic, and personal care products. They serve as bridges between inorganic or organic substrates and organic/polymeric matrices. They are also versatile intermediates and can be used for a variety of synthetic applications. They do not exist naturally and have to be synthesized. Evaluation of intermediates and products resulting from the synthesis processes of organosilanes can be challenging. In this study, gas chromatography with vacuum ultraviolet spectroscopic detection (VUV) was used to analyze Si-containing compounds that are commercially available or were synthetically prepared. VUV measures full scan absorption in the range of 120-240 nm, a region that provides unique absorption signatures for chemical compounds. VUV absorption spectra of organosilanes showed rich and featured characteristics in this wavelength range. Theoretical computations of VUV absorption spectra based on time-dependent density functional theory were also explored as a complementary tool for identification. In addition, the synthesis process of isomeric benzodioxasiline compounds (ortho-, meta-, and para-) was monitored by GC-VUV. It was demonstrated that GC-VUV can be used for easy and rapid differentiation of organosilanes, including structural isomers.

Diversely substituted arylsilyl triflates, as aryne precursors for aryne cycloaddition reactions, were accessed from benzodioxasilines. Catalytic reductive C H ortho- silylation of phenols with traceless acetal directing groups was exploited to prepare benzodioxasilines. Sequential addition of MeLi and then trifluoromethanesulfonic anhydride to benzodioxasilines provided arylsilyl triflates in a single pot. Notably, this approach was successfully utilized to prepare sterically hindered 1,2,3-trisubstituted arylsilyl triflates, which ultimately underwent fluoride-mediated aryne cycloaddition.

Background Contaminated surfaces are a critical risk factor for transmitting infectious disease. Current disinfection products provide short-term antimicrobial action; however, these surfaces can be re-contaminated within hours after cleaning. To address this limitation, long-lasting antimicrobial polymer coatings have been developed as an adjunct to traditional disinfecting and cleaning protocols. Due to the micro-scale thickness and transparency of the coating, confirmation of its presence on surfaces is difficult with conventional methods; therefore, this study explores a novel approach to measuring durable polymer coatings on stainless steel coupons to validate their presence and relative antimicrobial activity. Methods In this study, we utilized a hand-held X-ray fluorescence spectroscopy (XRF) analyzer to quantitatively evaluate the amount of antimicrobial polymer coating deposited on stainless steel test surfaces. Stainless steel surfaces with amounts of coating ranging from 0.12 to 3.60 mg/in.2 were analyzed for their XRF profile using a hand-held spectrometer. Additionally, the relationship between the XRF spectra and antimicrobial activity was evaluated using a modified version of an existing sanitization protocol for hard surfaces using Staphylococcus epidermidis as the test organism. Results Comparison of the amount of antimicrobial polymer coating (in mg) and the XRF values (photon count) revealed a calibration curve with a high degree of linearity (R2 = 0.993) especially for surfaces that had lower mass (Figure 1). In addition, the relationship between XRF values and antimicrobial efficacy also were found to be well-correlated with a logarithmic trend (R2 = 0.9308) (Figure 2). Conclusion The observed trends between coating mass, XRF value and antimicrobial efficacy suggests that these analytical techniques are viable options for determining the presence of invisible antimicrobial polymer coatings. Additionally, laboratory-based calibration curves based on XRF values can be used to predict the level of antimicrobial activity of surfaces that have been treated with polymer coatings. These findings suggest that the use of a hand-held XRF spectrometer can be a rapid and cost-effective method for assessing the presence and efficacy of polymer coatings. Disclosures All authors: No reported disclosures.

Because of the importance of hydrogen atom transfer (HAT) in biology and chemistry, there is increased interest in new strategies to perform HAT in a sustainable manner. Here, we describe a sustainable, net redox-neutral HAT process involving hydrosilanes and alkali metal Lewis base catalysts — eliminating the use of transition metal catalysts — and report an associated mechanism concerning Lewis base-catalysed, complexation-induced HAT (LBCI-HAT). The catalytic LBCI-HAT is capable of accessing both branch-specific hydrosilylation and polymerization of vinylarenes in a highly selective fashion, depending on the Lewis base catalyst used. In this process, earth abundant, alkali metal Lewis base catalyst plays a dual role. It first serves as a HAT initiator and subsequently functions as a silyl radical stabilizing group, which is critical to highly selective cross-radical coupling. EPR study identified a potassiated paramagnetic species and multistate density function theory revealed a high HAT character, yet multiconfigurational nature in the transition state of the reaction., Graphical Abstract

This paper presents a microfluidic chemical reaction using an electrowetting-on-dielectric (EWOD) digital microfluidic device. Despite a number of chemical/biological applications using EWOD digital microfluidic devices, their applications to organic reactions have been seriously limited because most of the common solvents used in synthetic organic chemistry are not compatible with EWOD devices. To address this unsolved issue, we first introduce a novel technique using an "engine-and-cargo" system that enables the use of non-movable fluids (e.g., organic solvents) on an EWOD device. With esterification as the model reaction, on-chip chemical reactions were successfully demonstrated. Conversion data obtained from on-chip reactions were used to characterize and optimize the reaction with regard to reaction kinetics, solvent screening, and catalyst loading. As the first step toward on-chip combinatorial synthesis, parallel esterification of three different alcohols was demonstrated. Results from this study clearly show that an EWOD digital microfluidic platform is a promising candidate for microscale chemical reactions.

We report a redox-neutral, catalytic C–C activation of cyclopropyl acetates to produce silicon-containing five-membered heterocycles in a highly region-and chemoselective fashion. The umpolung α-selective silylation leading to dioxasilolanes is opposed to contemporary β-selective C–C functionalization protocols of cyclopropanols. Lewis base activation of dioxasilolanes as α-silyl carbinol equivalents undergoes the unconventional [1,2]-Brook rearrangement to form tertiary alcohols. Notably, mechanistic studies indicate that an electrophilic metal-π interaction harnessing highly fluorinated [Formula: see text] catalyst permitted a low-temperature C–C activation.

As microfluidic systems play important roles to advance chemical synthesis applications in pharmaceutical and life science fields, the demand for fully-automated chemical synthesis work cycles grows. A successful automation of chemical synthesis with high yields requires not only executing sequential steps of organic chemical reactions, but also simple and adaptive purification (i.e., workup) techniques in each step. Despite recent advances in microreactor technologies, seamlessly integrating reactions and work-up toward a fully-automated chemical synthesis platform is an unmet challenge. In this study, we have demonstrated an electrowetting-on-dielectric (EWOD) digital microfluidic device (DMF) as an efficient in-line work-up tool for organic chemical synthesis reactions. The model protocol performed on EWOD DMF involves an acid-base workup, liquid-liquid extraction (LLE), and in-line solvent-swap. Device operation parameters of each reactant and unit process have been optimized. This study manifests the capacity of an EWOD device to transform into a drug discovery platform, particularly by hosting synthetically important reactions that require complicated work-up sequences.

A new, highly selective, bond functionalization strategy, achieved via relay of two transition metal catalysts and the use of traceless acetal directing groups, has been employed to provide facile formation of C–Si bonds and concomitant functionalization of a silicon group in a single vessel. Specifically, this approach involves the relay of Ir-catalyzed hydrosilylation of inexpensive and readily available phenyl acetates, exploiting disubstituted silyl synthons to afford silyl acetals and Rh-catalyzed ortho-C–H silylation to provide dioxasilines. A subsequent nucleophilic addition to silicon removes the acetal directing groups and directly provides unmasked phenol products and, thus, useful functional groups at silicon achieved in a single vessel. This traceless acetal directing group strategy for catalytic ortho-C–H silylation of phenols was also successfully applied to preparation of multisubstituted arenes. Remarkably, a new formal α-chloroacetyl directing group has been developed that allows catalytic reductive C–H silylation of sterically hindered phenols. In particular, this new method permits access to highly versatile and nicely differentiated 1,2,3-trisubstituted arenes that are difficult to access by other catalytic routes. In addition, the resulting dioxasilines can serve as chromatographically stable halosilane equivalents, which allow not only removal of acetal directing groups but also introduce useful functional groups leading to silicon-bridged biaryls. We demonstrated that this catalytic C–H bond silylation strategy has powerful synthetic potential by creating direct applications of dioxasilines to other important transformations, examples of which include aryne chemistry, Au-catalyzed direct arylation, sequential orthogonal cross-couplings, and late-stage silylation of phenolic bioactive molecules and BINOL scaffolds.

A new, highly selective, bond functionalization strategy, achieved via relay of two transition metal catalysts and the use of traceless acetal directing groups, has been employed to provide facile formation of C–Si bonds and concomitant functionalization of a silicon group in a single vessel. Specifically, this approach involves the relay of Ir-catalyzed hydrosilylation of inexpensive and readily available phenyl acetates, exploiting disubstituted silyl synthons to afford silyl acetals and Rh-catalyzed ortho-C–H silylation to provide dioxasilines. A subsequent nucleophilic addition to silicon removes the acetal directing groups and directly provides unmasked phenol products and, thus, useful functional groups at silicon achieved in a single vessel. This traceless acetal directing group strategy for catalytic ortho-C–H silylation of phenols was also successfully applied to preparation of multisubstituted arenes. Remarkably, a new formal α-chloroacetyl directing group has been developed that allows catalyti...

A convenient scalable transformation of multiple challenging aryl, hetaryl, alkyl, and alkinyl esters as well as diesters into silyl acetals and the in-situ transformation of the latter into enoates is elaborated.

A Lewis base promoted deprotonative pronucleophile addition to silyl acetals has been developed and applied to the iridium-catalyzed reductive Horner–Wadsworth–Emmons (HWE) olefination of esters and the chemoselective reduction of the resulting enoates. Lewis base activation of silyl acetals generates putative pentacoordinate silicate acetals, which fragment into aldehydes, silanes, and alkoxides in situ. Subsequent deprotonative metalation of phosphonate esters followed by HWE with aldehydes furnishes enoates. This operationally convenient, mechanistically unique protocol converts the traditionally challenging aryl, alkenyl, and alkynyl esters to homologated enoates at room temperature within a single vessel.

One-pot, three-component condensation of 2-hydroxybenzaldehyde derivatives, primary amines with alkyl isocyanides is reported. N-alkyl-2-(2-hydroxyphenyl)-2-iminoacetamide derivatives are generated presumably via the preliminary formation of N, N′-disubstituted benzo[b]furan-2,3-diamines and subsequent oxidation with molecular oxygen.

The reaction proceeds via cyclic silyl acetal intermediates that can be obtained as major products in the case of ortho-substituted aryl esters (XII).

This work describes the design and application of a single-pot, reductive arene C–H silanolization of aromatic esters for synthesis of ortho-formyl arylsilanols. This strategy involves a sequence of two transition metal (Ir and Rh)-catalyzed reactions for reductive arene ortho-silylation directed by hydridosilyl acetals and hydrolysis.