Silicon is the second most abundant element on the earths surface, whereby inorganic silanols (SiOH) make up the reactive hydroxyl groups on the surface of minerals, zeolites, and silica gel. The acidic silanol groups [1] are known to be capable of hydrogen bonding to small molecules for heterogeneous catalysis and separation chemistry, but the discrete surface-molecule interactions are not well understood.[2] Silanediols R 2 Si(OH) 2 are of particular interest as they contain a geminal diol bonding motif that is not commonly accessible for carbon analogues, but they represent a synthetic challenge due to their rapid rates of self-condensation. While condensation is advantageous for the synthesis of siloxane polymers, metallosiloxanes, and silesquioxanes, [3] it creates a barrier that may hinder researchers from exploring the properties and applications of discrete silanediols. [4] Recent studies demonstrate that silanols can function as isosteres and transition-state analogues in drug design, in which the enhanced acidity of the silanol can improve binding to a receptor.[5] Small molecules containing silanol and silanediol groups may be useful as models to understand local surface sites and reactivity of silica materials for catalysis, and also to design new homogeneous small-molecule catalysts.We seek to understand the hydrogen bonding patterns and interactions between organic silanediols with carbonyls for applications to catalysis and molecular recognition. Hydrogen bonding interactions play an important role in molecular recognition and metal-free catalysis, and are frequently used in nature for structural organization and enzyme activity.[6] Previous structural studies have demonstrated the hydrogen bonding networks that silanediols can attain through dual donor and acceptor interactions, [4, 7] and also the ability to hydrogen bond with chloride anions for molecular recognition.[8] Studies of silanetriols have shown that amines can complex with and stabilize silanetriols.[9]Here we describe the synthesis and structural studies of organic silanediols for small-molecule hydrogen bonding activation of carbonyl compounds.[10] We are particularly interested in studying bulky silanediols that do not readily undergo condensation reactions.[11] We have performed crystallization and NMR-binding experiments to investigate the hydrogen bonding interactions in both solid-state and solution for molecular recognition and the design of new catalysts. This is the first study of neutral Lewis basic carbonyl compounds with silanediols.We have synthesized a series of bulky silanediols 2-4 that incorporate electron-withdrawing groups to enhance acidity while incorporating steric effects to overcome condensation reactions. Due to the synthetic challenge, the chemical space for silanediols is largely unexplored, and silanediols 2-4 represent new structures.[4] The mesityl group (Mes) was incorporated to prevent formation of disiloxanediols and higher order siloxanes.[12] Incorporating a mesityl group also provides enhanced so...

Dichloromethane (DCM), hexane, ethyl acetate (EtOAc), and diethyl ether (Et 2 O) were obtained from EMD Chemicals. Toluene (PhMe), methanol (MeOH), and tetrahydrofuran (THF) were obtained from Fisher Scientific. Palladium on carbon (5 wt% and 10 wt%), anhydrous magnesium sulfate, (-)-sparteine, acetaldehyde, and 2-mesitylmagnesium bromide solution (1.0 M in Et 2 O) were acquired from Sigma Aldrich. Dimethoxyethane, trichlorosilane, secbutyllithium (1.3 M in cyclohexane/hexanes (98/2)), and ytterbium (III) triflate hydrate were purchased from Acros Organics.tert-butyl-1-pyrrolidine-carboxylate, ammonium hexafluorosilicate, amberlyst-A21, 1-methylisatin, and 1-phenylisatin were purchased from Alfa-Aesar. Diphenylchlorosilane was obtained from Gelest. 4-chloroisatin was obtained from TCI America. Commercially available reagents were purchased and used without further purification unless otherwise indicated. sec-Butyllithium was titrated before use with diphenylacetic acid to obtain accurate concentration for reactions.Reactions were analyzed by thin layer chromatography (TLC) on EMD glass plates that were pre-coated with silica gel 60 F254, and the reactions were purified by column chromatography using Acros silica gel 60 Å (0.035-0.070 mm) or Sigma Aldrich silica gel 150 Å grade 62 (60-200 mesh). The following abbreviations are used throughout: ethyl acetate (EtOAc), acetonitrile (MeCN), dichloromethane (DCM), isopropanol (IPA), methanol (MeOH), enantiomeric excess (ee), triethylamine (Et 3 N). All aldol reactions were performed in glass vials with Teflon caps and exposure to atmospheric conditions.All 1 H and 13 C NMR spectra were recorded at ambient temperature at 300, 400, and 600 MHz or 75, 100, and 150 MHz, respectively. 19 F NMR spectra were recorded at ambient temperature at 282 MHz. 29 Si NMR spectra were recorded at ambient temperature at 119 MHz. The 1 H spectral data are reported as follows: chemical shift in parts per million downfield from tetramethylsilane on the δ scale, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; s, septet; m, multiplet; dd, doublet of doublets, and b, broadened), coupling constant (Hz), and integration. Carbon NMR chemical shifts are reported in ppm from tetramethylsilane with the solvent reference employed as the internal standard (deuterochloroform (CDCl 3 )) at 77.16 ppm. Unless otherwise indicated, all chiral stationary phase HPLC analyses were performed with a Daicel CHIRALCEL OD-H column (4.6 x 250mm, 5 µm), CHIRALPAK AD-H column (4.6 x 250 mm, 5 µm), or CHIRALPAK AS-H column (4.6 x 250 mm, 5 µm), with corresponding guard columns, with a flow rate of 0.5 -1.0 mL/min (2-propanol/hexanes isocratic system) using a photodiode array detector and at various column oven temperature. Compounds were analyzed by HRMS on an orbitrap spectrometer using electrospray ionization in the positive ion mode at >60000 resolutions and using typical ESI source values. These settings result in mass accuracies <5 ppm. Some compounds were analyzed by LRMS in the positive ion mode o...

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.

Cyclic azasilanes have been synthesized for the purpose of developing coupling agents appropriate for a variety of nanotechnologies including surface modification of nanoparticles, nanocrystals, mesoporous materials and substrates. N‐Methyl‐aza‐2,2,4‐trimethylsilacyclopentane is representative of this class of compounds. Preliminary data for the treatment of inorganic surfaces, including nanoparticles and oxidized silicon wafers, with cyclic azasilanes suggest high‐density monolayer deposition by a ring‐opening reaction. Cyclic azasilanes contain a cryptic amine functionality that can perform a subsequent tandem coupling reaction with functional molecules after the surface‐triggered ring‐opening reaction, allowing for a one‐pot self‐assembly route on nanostructures. Tandem coupling reactions are demonstrated via addition reactions of the cryptic amine with epoxy and acrylate systems.

A library of novel, propeller-shaped dispirotriheterocyclic isoxazolinopiperidinochromanones is reported. Each rigid dispirotriheterocycle was prepared in five linear steps from commercially available tert-butyl 4-oxopiperidine-1-carboxylate and various derivatives of 1-(2-hydroxyphenyl)ethanone, benzaldehyde oxime, and carboxylic acids. Computational chemistry was employed to analyze the three-dimensional geometries of these dispirotriheterocycles, as well as to generate chemoinformatic bioavailability data. X-ray crystallographic structure determination verified the regioselectivity of the nitrile oxide 1,3-dipolar cycloaddition reaction. The resulting library of compounds has been added to the National Institutes of Health repository (approximately 10 mg of each with > or =90% purity) for pilot-scale biomedical studies with bioassay data available at the National Center for Biotechnology Information PubChem database.

Thiasilacyclopentane (TSCP) and azasilacyclopentane (ASCP) heteroatom cyclics have proven capable of rapidly converting hydroxylated surfaces to functionalized surfaces in inorganic click reactions. In this work, we demonstrate that the use of these reagents can be extended to "simultaneous doubleclicking" when both inorganic and organic substrates are present at the onset of the reaction. The simultaneous double-click depends on a first ring-opening click with an inorganic substrate that is complete in ∼1 s at 30 °C and results in the reveal of a cryptic mercaptan or secondary amine group, which can then participate in a second click with an organic substrate. TSCPs and ASCPs can take part in tandem double-click reactions in which the organic substrate is added to the reaction mixture after the initial inorganic click reaction is completed. Additionally, ASCPs with exocyclic functionality, specifically N-alkenyl-, N-aminoalkyl, and N-alkynyl-ASCPs, are shown to be options for tandem double-clicking in which functionalization proceeds in two independent steps and the sequence of the double-click reaction can be reversed.

Silyl Fluoride Electrophiles for the Enantioselective Synthesis of Silylated Pyrrolidine Catalysts. -(-)-Sparteine-mediated treatment of the pyrrole (I) with the silyl fluorides (II) allows efficient and highly stereoselective access to the products (III). The latter can smoothly be converted into enantiopure pyrroles by recrystallization or trituration. The derivative (IVa) and the free amine (SIL) efficiently promote the asymmetric Michael addition of aldehydes to nitrostyrenes. -(JENTZSCH, K. I.; MIN, T.; ETCHESON, J. I.; FETTINGER, J. C.; FRANZ*, A. K.; J. Org. Chem. 76 (2011) 17, 7065-7075, http://dx.doi.org/10.1021/jo200991q ; Dep. Chem., Univ. Calif., Davis, CA 95616, USA; Eng.) -Jannicke 01-158