1,3-Disiloxanediols are effective hydrogen-bonding catalysts that exhibit enhanced activity relative to silanediols and triarylsilanols. The catalytic activity for a series of 1,3-disiloxanediols, including naphthyl-substituted and unsymmetrical siloxanes, has been quantified and compared relative to other silanol and thiourea catalysts using the Friedel Crafts addition of indole to trans-β-nitrostyrene. An in-depth kinetic study using reaction progress kinetic analysis (RPKA) has been performed to probe the catalyst behavior of 1,3-disiloxanediols. The data confirm that the disiloxanediol-catalyzed addition reaction is first order in catalyst over all concentrations studied with no evidence of catalyst self-association. 1,3-Disiloxanediols proved to be robust and recoverable catalysts with no deactivation under reaction conditions. No product inhibition is observed, and competitive binding studies with nitro-containing additives suggest that 1,3-disiloxanediols bind weakly to nitro groups but are strongly activating for catalysis.

New methodology has been developed for the Lewis acid catalyzed synthesis of malonamides. First, the scandium(III)-catalyzed addition of diverse nucleophiles (e.g., indoles, N,N-dimethyl-m-anisidine, 2-ethylpyrrole, and 2-methylallylsilane) to coumarin-3-carboxylates has been developed to afford chromanone-3-carboxylates in high yields as a single diastereomer. Upon investigating a subsequent lanthanum(III)-catalyzed amidation reaction, a new multicomponent reaction was designed by bringing together coumarin-3-carboxylates with indoles and amines to afford indolylmalonamides, which were identified to exhibit fluorescent properties. The photophysical properties for selected compounds have been analyzed, including quantum yield, molar absorptivity, and Stokes shift. Synthetic studies of several reaction byproducts involved in the network of reaction equilibria for the three-component reaction provide mechanistic insight for the development of this methodology.

A Lewis acid-catalyzed stereoselective [3+2] annulation of crotylsilanes with iminooxindoles is reported to access 2,3′-pyrrolidinyl spirooxindoles with four stereocenters. The addition of NaBArF significantly enhances reactivity, allowing either metal salts or acidic clay to be effective catalysts for the stereoselective reaction.

X-ray crystallography showcases the distinct self-association and hydrogen-bonding patterns of organic silanediols, R2Si(OH)2, with bifunctional heterocycles for supramolecular assembly. Diffusion-ordered spectroscopy (DOSY) studies identify the dominant hydrogen-bonding patterns and structures in solution, which correlate with solid-state patterns at high concentrations.

A stereoselective cyclization between alkylidene oxindoles and 5-methoxyoxazoles has been developed using catalytic titanium(IV) chloride (as low as 5 mol %) to afford spiro[3,3′-oxindole-1-pyrrolines] in excellent yield (up to 99%) and diastereoselectivity (up to 99:1). Using a chiral scandium(III)–indapybox/BArF complex affords enantioenriched spirooxindole-1-pyrrolines where a ligand-induced reversal of diastereoselectivity is observed. This methodology is further demonstrated for the synthesis of pyrrolines from malonate alkylidene and coumarin derivatives.

Spirocycles provide an exciting platform to develop and understand the reactivity and selectivity for a wide variety of catalysts while affording diverse strategies to access molecules with important applications. This review features recent examples in which a spirocenter is formed within the key step of a catalytic asymmetric process, in either an intramolecular or intermolecular fashion. Examples highlight notable spirocyclization strategies and compare the reactivity and selectivity for different classes of chiral organocatalysts and organometallic catalysts.Keywords: asymmetric; catalytic; spirocenter; spirocyclic; spiroketals; spirolactones; spirooxindole

We report the Lewis acid catalyzed additions of allylsilanes to N-Boc-iminooxindoles and the formation of novel silicon-containing spirocarbamates via intramolecular trapping of a β-silyl carbocation by an N-Boc group. Several transformations display the synthetic utility of these spirocarbamate oxindoles, including a reductive cyclization to access new silylated furoindoline derivatives.

The incorporation of silicon and synthesis of organosilicon small molecules provide unique opportunities for medicinal applications. The biological investigation of organosilicon small molecules is particularly interesting because of differences in their chemical properties that can contribute to enhanced potency and improved pharmacological attributes. Applications such as inhibitor design, imaging, drug release technology, and mapping inhibitor binding are discussed.

Here we describe the first phenotypic screening with microalgae to study lipid metabolism and to discover organic small molecules as chemical triggers that increase growth and lipid production. A microplate assay has been developed for analysis of intracellular lipids using Nile Red fluorescence in order to screen a collection of diverse bioactive organic molecules (e.g., kinase inhibitors) with four strains of oleaginous microalgae (Nannochloropsis salina, Nannochloropsis oculata, Nannochloris sp., and Phaeodactylum tricornutum). Several small molecules identified in microplate screening increased lipid productivity >200% without decreasing growth and biomass production. Selected compounds were further investigated in the context of larger batch culture experiments (e.g., 500 mL) and demonstrated to increase lipid levels (up to 84%) while maintaining or increasing the specific growth rate. Bioactive molecules such as forskolin and quinacrine were identified as promising probes of microalgae lipid pathways. We have also determined that common antioxidants such as epigallocatechin gallate and butylated hydroxyanisole (BHA) increase lipid productivity and may represent new probes of oxidative signaling pathways for photooxidative protection.

A new bifunctional catalyst containing a silanol group has been designed and synthesized with high enantioselectivity in three steps. The hydrogen-bonding properties of this pyrrolidinylsilanol have been investigated using NMR binding studies and electrospray ionization mass spectrometry (ESI-MS) analysis. The ability of the silanol group to activate an electrophile and afford enantiocontrol through hydrogen-bond directing effects has been demonstrated using an enantioselective aldol reaction with isatin and acetaldehyde, affording up to 88% ee.Keywords: aldol; asymmetric catalysis; bifunctional; hydrogen bonding; oxindole; silanol

The importance of cooperative hydrogen-bonding effects and SiOH-acidification is described for silanediol catalysis. NMR binding, X-ray, and computational studies provide support for a unique dimer resulting from silanediol self-recognition. The significance of this cooperative hydrogen-bonding is demonstrated using novel fluorinated silanediol catalysts for the addition of indoles and N,N-dimethyl-m-anisidine to trans-β-nitrostyrene.

The scandium(III)-catalyzed enantioselective Hosomi–Sakurai allylation of isatins with various substituted allylic silanes is described. A catalyst loading as low as 0.05 mol % is utilized at room temperature to afford the 3-allyl-3-hydroxy-2-oxindoles in excellent yields and enantioselectivity up to 99% ee, including a demonstration of a gram-scale reaction. The effects of additives and varying silyl groups were explored to demonstrate the scope and application.

A facile, rapid, and noninvasive method for monitoring transesterification of acylglycerols for the application of biodiesel production is reported. High-field NMR spectroscopic analysis prevents incorrect and overintegration of signals that have previously been combined due to crowding on low-field NMR spectrometers. Using high resolution NMR, a new and more accurate equation utilizing a nonoverlapping signal is presented for calculating biodiesel conversion. Here, we demonstrate the kinetic acquisition of high-resolution NMR spectra for real-time monitoring of the consumption and formation of triacylglycerols, diacylglycerols, and fatty acid methyl esters in biodiesel production. This method of reaction monitoring takes place on small scale in a standard NMR tube, is acquired with existing laboratory instruments, and avoids taking aliquots from a reaction. By comparing different catalysts and conditions, this method facilitates the selection/optimization of catalysts and may improve quality in compliance with fuel standards by assessing the reaction composition for models of an industrial transesterification system. Using this method, H2SO4, NaOH, and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (a bifunctional, nonionic base) have been compared as catalysts for transesterification.

A strategy for the efficient two-step synthesis of triazole derivatives of oxindoles and spirooxindoles is presented. Using a common set of N-propargylated isatins, a series of mechanistically distinct stereoselective reactions with different combinations of nucleophiles and catalysts provide access to diverse hydroxy-oxindoles, spiroindolones, and spirocyclic oxazoline structures. The resulting N-propargylated oxindoles are then converted to triazoles using copper-catalyzed azide–alkyne cycloaddition (CuAAC) reactions. Overall, this strategy affords a 64-member pilot-scale library of diverse oxindoles and spirooxindoles.Keywords: heterocycles; isatins; oxazolines; oxindoles; spiroindolones; spirooxindoles; triazoles

This work describes efforts to incorporate and evaluate the use of a YouTube writing assignment in large lecture classes to personalize learning and improve conceptual understanding of chemistry through peer- and self-explanation strategies. Although writing assignments can be a method to incorporate peer- and self-explanation strategies, this method is not often incorporated in large lecture classes and lower-division science courses. This work primarily focuses on a YouTube “video script” writing assignment where a student selects an organic chemistry concept and describes how they would “teach” or creatively explain the concept to their fellow classmates using real-world examples in a popular YouTube video format. In a more elaborate version of the assignment, students then proceed to make a YouTube video based on this written assignment. Subsequent details and feedback about the assignment are also presented.Keywords: Communication/Writing; First-Year Undergraduate/General; Multimedia-Based Learning; Organic Chemistry; Second-Year Undergraduate; Student-Centered Learning;

The synthesis, isolation, and hydrogen-bonding properties of a series of amide-containing silanediols are described, including an enantioenriched silanediol. By incorporation of a 2,4,6-trimethylphenyl (mesityl) group, these functionalized silanediols are isolable by column chromatography and stable in the presence of standard acids (e.g., AcOH) and bases (e.g., NH4OH). NMR spectroscopy and X-ray crystallography provide evidence for the conformational rigidity and binding properties of amido-silanediols based on the parameters (e.g., sterics, hybridization, and ring size of hydrogen bonding) that affect intra- and intermolecular hydrogen bonding. Pyridine binding studies demonstrate that these conformational effects have implications for the existence of single versus multiple modes of hydrogen bonding.

The indium(III)-catalyzed enantioselective and regioselective addition of pyrroles to isatins is described. The effects of metal and solvent on the reactivity and selectivity are compared and discussed, demonstrating that the indium(III)–indapybox complex provides the most effective catalyst. A case of divergent reactivity between pyrroles and indoles is presented.

A regio- and stereoselective cyclization between isatins and 5-methoxyoxazoles has been developed using catalytic titanium(IV) chloride (10 or 20 mol %) to afford spiro[3,3′-oxindoleoxazolines] in excellent yield (up to 99%) and diastereoselectivity (dr >99:1). Substitution at the 4-position of the oxazole controls nucleophilic attack to provide either the 2-oxazoline or 3-oxazoline spirocycle with excellent (>99:1) regiocontrol.

The condensation cyclization between isatins and 5-methoxy tryptamine catalyzed by chiral phosphoric acids provides spirooxindole tetrahydro-β-carboline products in excellent yields (up to 99%) and enantioselectivity (up to 98:2 er). A comparison of catalysts provides insight for the substrate scope and factors responsible for efficient catalytic activity and selectivity in the spirocyclization. Chiral phosphoric acids with different 3,3′-substitution on the binaphthyl system and opposite axial chirality afford the spiroindolone product with the same absolute configuration.

The fundamental properties of a series of organic monosilanols, silanediols, disiloxanediols, and known hydrogen-bonding organocatalysts have been examined in the gas phase using computational and experimental mass spectrometry methods. The organosilicon diol molecules contain dual hydrogen-bonding groups that were designed as potential hosts and hydrogen-bonding catalysts. Newly measured acidities are reported, and implications regarding solvent effects, catalysis, and molecular recognition are discussed.

Chiral silylated pyrrolidine catalysts are obtained in high yield and enantioselectivity by sparteine-mediated lithiation of N-Boc-pyrrolidine and addition to silyl fluoride electrophiles. The activity and enantioselectivity of a new tert-butyldiphenylsilylpyrrolidine catalyst has been demonstrated for various asymmetric Michael reactions at 5 mol % catalyst loading and affords up to 99% ee for asymmetric Michael reactions with aldehydes and nitro-olefins. Acetaldehyde donors proceed with yields up to 77% and enantioselectivities up to 96% ee, avoiding common side reactions that often lower yields. Insight into the mechanism of pyrrolidine-based catalysts is provided by demonstrating ESI mass spectrometry evidence for activation of a nitro acceptor by formation of a hydrogen-bonding adduct with the catalyst amine. Analysis of reaction intermediates using mass spectrometry provides evidence that the pyrrolidine catalyst also plays a role in activating nitro-olefins through hydrogen-bonding.

•LSCM is used to study lipid storage patterns in microalgae.•P. tricornutum accumulates lipids by merging with existing lipid bodies.•T. suecica accumulates lipids by synthesizing new lipid bodies.•Nile Red analysis in microplates identifies optimal harvest date for microalgal lipids.Microalgae contain lipid bodies (LBs) composed of triacylglycerols, which can be converted to biodiesel. Here we demonstrate a method to study the accumulation patterns of LBs in different microalgae strains and culture conditions utilizing laser scanning confocal microscopy (LSCM) with BODIPY 505/515 (4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene) staining, in parallel with Nile Red (9-diethylamino-5H-benzo-a-phenoxazine-5-one) fluorescence analysis of intracellular lipids in microplates. Phaeodactylum tricornutum and Tetraselmis suecica were selected as model organisms and monitored throughout the growth phases in standard and nitrogen-deficient growth conditions. Utilizing image quantification techniques, the number and morphology of LBs suggest that P. tricornutum accumulates lipids by merging with existing LBs, while T. suecica synthesizes new LBs. We observed that T. suecica accumulates a higher number of LBs and total volume of lipids per cell, while P. tricornutum accumulates only 1–2 LBs with a larger volume per LB. LSCM analysis complements Nile Red (NR) methods because LSCM provides three-dimensional images of lipid accumulation at a cellular level, while NR analysis can quickly monitor the total levels of intracellular lipids for phenotypic screening. Using NR analysis, we have observed that the optimal harvest date for P. tricornutum and T. suecica in standard cultivation conditions is 24 and 42 days, respectively. Comparison with nitrogen-deficient growth conditions is utilized as a model to confirm that LSCM and NR analysis can be used to study lipid storage and productivity for diverse growth conditions and various strains of microalgae.Download full-size image

X-ray crystallography showcases the distinct self-association and hydrogen-bonding patterns of organic silanediols, R2Si(OH)2, with bifunctional heterocycles for supramolecular assembly. Diffusion-ordered spectroscopy (DOSY) studies identify the dominant hydrogen-bonding patterns and structures in solution, which correlate with solid-state patterns at high concentrations.

A Lewis acid-catalyzed stereoselective [3+2] annulation of crotylsilanes with iminooxindoles is reported to access 2,3′-pyrrolidinyl spirooxindoles with four stereocenters. The addition of NaBArF significantly enhances reactivity, allowing either metal salts or acidic clay to be effective catalysts for the stereoselective reaction.