Catalytic Net Oxidative C-C Activation and Silylation of Cyclopropanols with a Traceless Acetal Directing Group.

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 ß-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,ß-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 ß-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,ß-dianion equivalent, delivers α,ß-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,ß-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.

Gas chromatography-vacuum ultraviolet spectroscopic analysis of organosilanes.

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.

Catalytic hydrogen atom transfer from hydrosilanes to vinylarenes for hydrosilylation and polymerization.

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.

On-chip organic synthesis enabled using an engine-and-cargo system in an electrowetting-on-dielectric digital microfluidic device.

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.

Umpolung α-Silylation of Cyclopropyl Acetates via Low-Temperature Catalytic C-C Activation.

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 ß-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 Tp (CF 3 ) 2 Rh(nbd) catalyst permitted a low-temperature C-C activation.

Synthesis of Macrocycles Derived from Substituted Triazines.

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.

Aryne cycloaddition reactions of benzodioxasilines as aryne precursors generated by catalytic reductive ortho-C-H silylation of phenols with traceless acetal directing groups.

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.

Catalytic Reductive ortho-C-H Silylation of Phenols with Traceless, Versatile Acetal Directing Groups and Synthetic Applications of Dioxasilines.

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.

Lewis Base Activation of Silyl Acetals: Iridium-Catalyzed Reductive Horner-Wadsworth-Emmons Olefination.

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.

Reductive arene ortho-silanolization of aromatic esters with hydridosilyl acetals.

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.