Rearrangement of epoxynitriles: a convenient homologation of acyclic and cyclic ketones to carboxylic acids

A convenient two-step homologation of both aliphatic and aromatic ketones to the corresponding carboxylic acid has been developed. First ketones were converted to epoxynitriles with the Darzens reaction. Second, a Lewis acid mediated rearrangement of these epoxynitriles with lithium bromide was achieved to give homologated secondary alkanoic acids (as well as aryl-alkanoic) in good yields. The mechanism and the scope of the rearrangement reaction were investigated. This strategy constitutes a two-step homologation of ketones to secondary carboxylic acids.     

Synthesis and Circular Dichroism of Both Enantiomers of 2-deuterofluoroacetic acid ( Fluoro[2H1]acetic acid)

Sharpless epoxidation of (E)-1-(trimethylsilyl)[1-²H₁]oct-1-en-3-o1 ( 3a ) yielded (1S,2S,3S)- and (1R,2R,3R)-1-(trimethylsilyl)-1,2-epoxy[1-²H₁]octan-3-ols ( 4a and 4b , resp.) which were converted in three steps into (S)- and (R)-fluoro[ ²H₁]acetic acid ( 7a and 7b , resp.) in good yields. Their high isotopic and optical purity was established by ¹H- and ¹⁹F-NMR, mass, and circular-dichroism spectroscopy.     

Use of a native affinity ligand for the detection of G proteins by capillary isoelectric focusing with laser-induced fluorescence detection

Affinity probe capillary isoelectric focusing (CIEF) with laser-induced fluorescence was explored for detection of Ras-like G proteins. In the assay, a fluorescent BODIPY FL GTP analogue (BGTPgammaS) and G protein were incubated resulting in formation of BGTPgammaS-G protein complex. Excess BGTPgammaS was separated from BGTPgammaS-G protein complex by CIEF using a 3-10 pH gradient and detected in whole-column imaging mode. In other cases, a single point detector was used to detect zones during the focusing step of CIEF using a 2.5-5 pH gradient. In this case, analyte peaks passed the detector in approximately 5 min at an electric field of 350 V/cm. Detection during focusing allowed for more reproducible assays at shorter times but with a sacrifice in sensitivity compared to detection during mobilization. Resolution was adequate to separate BGTPgammaS-Ras and BGTPgammaS-Rab3A complexes. Formation of specific complexes was confirmed by adding GTPgammaS to samples containing BGTPgammaS-G protein. GTPgammaS competed with BGTPgammaS for G protein binding sites resulting in decreased BGTPgammaS-G protein peak heights. The concentrating effect of CIEF enabled detection limits of 30 pM.     

Structural analysis of metal interactions with the dinucleotide duplex, dCG x dCG, using ion mobility mass spectrometry

The metal binding properties of the dinucleotide duplex, dCG x dCG, were analyzed in the gas phase with ion mobility mass spectrometry. Both MALDI and ESI were used to generate [M(dCG x dCG)]+ complexes. The collision cross section of each complex was measured in helium using ion mobility based methods and compared to calculated cross sections of theoretical structures. When metal cations classified as hard acids were combined with dCG x dCG, the [M(dCG x dCG)]+ complex organized into a globular structure. However, when soft acid metal cations were examined, a structure was observed where the two C-G base pairs were Watson-Crick bound.     

Exploring Regioselective Bond Cleavage and Cross‐Coupling Reactions using a Low‐Valent Nickel Complex

Recently, esters have received much attention as transmetalation partners for cross‐coupling reactions. Herein, we report a systematic study of the reactivity of a series of esters and thioesters with [{(dtbpe)Ni}₂(μ‐η²:η²‐C₆H₆)] (dtbpe=1,2‐bis(di‐tert‐butyl)phosphinoethane), which is a source of (dtbpe)nickel(0). Trifluoromethylthioesters were found to form η²‐carbonyl complexes. In contrast, acetylthioesters underwent rapid C_acyl?S bond cleavage followed by decarbonylation to generate methylnickel complexes. This decarbonylation could be pushed backwards by the addition of CO, allowing for regeneration of the thioester. Most of the thioester complexes were found to undergo stoichiometric cross‐coupling with phenylboronic acid to yield sulfides. While ethyl trifluoroacetate was also found to form an η²‐carbonyl complex, phenyl esters were found to predominantly undergo C_aryl?O bond cleavage to yield arylnickel complexes. These could also undergo transmetalation to yield biaryls. Attempts to render the reactions catalytic were hindered by ligand scrambling to yield nickel bis(acetate) complexes, the formation of which was supported by independent syntheses. Finally, 2‐naphthyl acetate was also found to undergo clean C_aryl?O bond cleavage, and although stoichiometric cross‐coupling with phenylboronic acid proceeded with good yield, catalytic turnover has so far proven elusive.     

Efficient polymer passivation of ligand‐stripped nanocrystal surfaces

Water‐dispersible, polymer‐wrapped nanocrystals are highly sought after for use in biology and chemistry, from nanomedicine to catalysis. The hydrophobicity of their native ligand shell, however, is a significant barrier to their aqueous transfer as single particles. Ligand exchange with hydrophilic small molecules or, alternatively, wrapping over native ligands with amphiphilic polymers is widely employed for aqueous transfer; however, purification can be quite cumbersome. We report here a general two‐step method whereby reactive stripping of native ligands is first carried out using trialkyloxonium salts to reveal a bare nanocrystal surface. This is followed by chemically directed immobilization of a hydrophilic polymer coating. Polyacrylic acids, with side‐chain grafts or functional end groups, were found to be extremely versatile in this regard. The resulting polymer‐wrapped nanocrystal dispersions retained much of the compact size of their bare nanocrystal precursors, highlighting the unique role of monomer side‐chain functionality to serve as effective, conformal ligation motifs. As such, they are well poised for applications where tailored chemical functionality at the nanocrystal's periphery or improved access to their surfaces is desirable. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012