Synergistic Peptide and Gold Catalysis: Enantioselective Addition of Branched Aldehydes to Allenamides

The combination of a peptide catalyst and a gold catalyst is presented for enantioselective addition reactions between branched aldehydes and allenamides. The two catalysts act in concert to provide γ,δ-enamide aldehydes bearing a fully substituted, benzylic stereogenic center – a structural motif common in many natural products and therapeutically active compounds – with good yields and enantioselectivities. The reaction tolerates a variety of alkyl and alkoxy substituted aldehydes and the products can be elaborated into several chiral building blocks bearing either 1,4- or 1,5- functional group relationships. Mechanistic studies showed that the conformational features of the peptide are important for both the catalytic efficiency and stereochemistry, while a balance of acid/base additives is key for ensuring formation of the desired product over undesired side reactions.     

Orientation and conformation of two [6]carbohelicenes in stretched polystyrene and a thermoresponsive polyaspartate

Two functionalized [6]carbohelicenes, one of which was also available in its two enantiomeric pure forms, were oriented in stretched polystyrene in CDCl₃, and in a recently introduced chiral thermoresponsive lyotropic polyaspartate (poly(benzyl)_0.5(phenethyl)_0.5-L-aspartate) in C₂D₂Cl₄. From the resulting ¹H,¹³C residual dipolar couplings, the helical pitch of a methylated [6]carbohelicene was determined and found to be in agreement with theoretical predictions and existing crystal structures (d(C2,C2′) ≈ 4.3 Å). For a second [6]carbohelicene with para-methoxyphenyl substituents, a clear conformational preference of the substituents was observed. The orientational properties of the two helicene enantiomers in the chiral polyaspartate are very similar, but both drastically change around 306 K. We suggest this behavior is due to an unusual phase transition in the liquid crystal.     

Call for Papers: GRC, CADD, and statistics, and all that

Molecular modeling and the art of computer-aided drug discovery seldom make much use of statistics, despite being fields that can not calculate important properties with great reliability. The 2013 CADD Gordon conference intends to examine what prevents a more effective use of statistics in routine modeling and to raise consciousness as to what is possible. Practical methods will be discussed, deeper issues in applying standard approaches addressed and research on successes and failures in other disciplines presented by invited experts.     

Efficient calculation of SAMPL4 hydration free energies using OMEGA,SZYBKI, QUACPAC,and Zap TK

Several submissions for the SAMPL4 hydration free energy set were calculated using OpenEye tools, including many that were among the top performing submissions. All of our best submissions used AM1BCC charges and Poisson–Boltzmann solvation. Three submissions used a single conformer for calculating the hydration free energy and all performed very well with mean unsigned errors ranging from 0.94 to 1.08 kcal/mol. These calculations were very fast, only requiring 0.5–2.0 s per molecule. We observed that our two single-conformer methodologies have different types of failure cases and that these differences could be exploited for determining when the methods are likely to have substantial errors.     

A rapid boundary perturbation algorithm for scattering by families of rough surfaces

In this paper we describe a novel algorithm for the computation of scattering returns by families of rough surfaces. This algorithm makes explicit use of the fact that some scattering profiles of engineering interest (e.g., traveling ocean waves) come in branches parameterized analytically by a bifurcation quantity. Our approach delivers recursions which not only can be implemented to yield a rapid, robust and high-order numerical scheme, but also give a new proof of analyticity of scattering quantities with respect to the bifurcation parameter of the surface family. The real advantage of this new approach is that it computes, in one step, the scattered field for all possible members of the family of surfaces. By contrast, other state-of-the-art schemes must restart when the returns from a new surface are desired, so that the cost of our new approach is greatly advantaged when the number of samples of the family reaches even modest values. Numerical results which verify the accuracy of our approach and demonstrate their utility in computing grating efficiencies scattered by traveling surface ocean waves are presented.     

Rhodium(III)-catalysed,redox-neutral C(sp2)-H alkenylation using pivalimide as a directing group with internal alkynes

In the presence of [RhCp¹Cl₂]₂, N-pivaloyl anilines react with internal alkynes to give the corresponding 2-alkenylpivalimides under redox neutral conditions through C-H activation. This redox neutral hydroarylation, which does not require an external organic acid, unlocks a regioselective synthetic route to 2-alkenyl anilines and is generally applicable to diversely substituted electron rich and electron poor pivalimides.     

The near edge structure of cubic boron nitride

We compare the near edge structure (NES) of cubic boron nitride (cBN) measured using both electron energy loss spectroscopy (EELS) and X-ray absorption spectroscopy (XAS) with that calculated using three commonly used theoretical approaches. The boron and nitrogen K-edges collected using EELS and XAS from cBN powder were found to be nearly identical. These experimental edges were compared to calculations obtained using an all-electron density functional theory code (WIEN2k), a pseudopotential density functional theory code (CASTEP) and a multiple scattering code (FEFF). All three codes were found to reproduce the major features in the NES for both ionisation edges when a core-hole was included in the calculations. A partial core hole (1/2 of a 1s electron) was found to be essential for correctly reproducing features near the edge threshold in the nitrogen K-edge and to correctly obtain the positions of all main peaks. CASTEP and WIEN2k were found to give almost identical results. These codes were also found to produce NES which most closely matched experiment based on χ² calculations used to qualitatively compare theory and experiment. This work demonstrated that a combined experimental and theoretical approach to the study of NES is a powerful way of investigating bonding and electronic structure in boron nitride and related materials.