Ilia A. Guzei

Enantioselective Bromolactonization of Conjugated (Z)-Enynes

A catalytic enantioselective syn-1,4-bromolactonization of conjugated (Z)-enynes was reported. Diastereomeric ratios >20:1 and up to 99% enantiomeric excesses were observed. Di-, tri-, and tetra-substituted bromoallenes were prepared together with lactone heterocycles efficiently and stereoselectively. Preliminary investigations suggest that the chiral catalyst may serve as a bifunctional reagent by interacting with both a carboxylic acid nucleophile and NBS electrophile.

Luminescent transition-metal-containing cyclophanes (“molecular squares”): covalent self-assembly, host-guest studies and preliminary nanoporous materials applications

Abstract An overview is given of the synthesis and characterization of a family of transition-metal cyclophanes containing rhenium tricarbonyl chloro corners and bridging diimine edges. The synthesis of both heterometallic (Re2M2,M = Pd,Pt) and homometallic (Re4) cyclophanes is described. Also briefly described are studies aimed at shedding light on the probable mechanism of high-yield assembly of homometallic molecular squares. The use of these cavity-containing assemblies as hosts in the condensed-phase binding of selected molecular guests is discussed. Also described are preliminary applications of the compounds as thin film nanoporous sensing elements. These studies suggest that the compounds may prove useful in mass-responsive or light-responsive volatile organic chemical sensing devices.

Allylic C−H Acetoxylation with a 4,5-Diazafluorenone-Ligated Palladium Catalyst: A Ligand-Based Strategy To Achieve Aerobic Catalytic Turnover

Pd-catalyzed C-H oxidation reactions often require the use of oxidants other than O(2). Here we demonstrate a ligand-based strategy to replace benzoquinone with O(2) as the stoichiometric oxidant in Pd-catalyzed allylic C-H acetoxylation. Use of 4,5-diazafluorenone (1) as an ancillary ligand for Pd(OAc)(2) enables terminal alkenes to be converted to linear allylic acetoxylation products in good yields and selectivity under 1 atm O(2). Mechanistic studies have revealed that 1 facilitates C-O reductive elimination from a π-allyl-Pd(II) intermediate, thereby eliminating the requirement for benzoquinone in this key catalytic step.

Stereospecific Synthesis of Conformationally Constrained γ-Amino Acids: New Foldamer Building Blocks That Support Helical Secondary Structure

A highly stereoselective synthesis of novel cyclically constrained gamma-amino acid residues is presented. The key step involves organocatalytic Michael addition of an aldehyde to 1-nitrocyclohexene. After aldehyde reduction, this approach provides optically active beta-substituted delta-nitro alcohols (96-99% ee), which can be converted to gamma-amino acid residues with a variety of substituents at the alpha position. We have used these new building blocks to prepare alpha/gamma-peptide foldamers that adopt a specific helical conformation in solution and in the solid state.

Extraordinarily Robust Polyproline Type I Peptoid Helices Generated via the Incorporation of α-Chiral Aromatic N-1-Naphthylethyl Side Chains

Peptoids, or oligomers of N-substituted glycines, are a class of foldamers that have shown extraordinary functional potential since their inception nearly two decades ago. However, the generation of well-defined peptoid secondary structures remains a difficult task. This challenge is due, in part, to the lack of a thorough understanding of peptoid sequence-structure relationships and, consequently, an incomplete understanding of the peptoid folding process. We seek to delineate sequence-structure relationships through the systematic study of noncovalent interactions in peptoids and the design of novel amide side chains capable of such interactions. Herein, we report the synthesis and detailed structural analysis of a series of (S)-N-(1-naphthylethyl)glycine (Ns1npe) peptoid homo-oligomers by X-ray crystallography, NMR spectroscopy, and circular dichroism (CD) spectroscopy. Four of these peptoids were found to adopt well-defined structures in the solid state, with dihedral angles similar to those observed in polyproline type I (PPI) peptide helices and in peptoids with α-chiral side chains. The X-ray crystal structure of a representative Ns1npe tetramer revealed an all cis-amide helix, with approximately three residues per turn, and a helical pitch of approximately 6.0 Å. 2D-NMR analysis of the length-dependent Ns1npe series showed that these peptoids have very high overall backbone amide K(cis/trans) values in acetonitrile, indicative of conformationally homogeneous structures in solution. Additionally, CD spectroscopy studies of the Ns1npe homo-oligomers in acetonitrile and methanol revealed a striking length-dependent increase in ellipticity per amide. These Ns1npe helices represent the most robust peptoid helices to be reported, and the incorporation of (S)-N-(1-naphthylethyl)glycines provides a new approach for the generation of stable helical structure in this important class of foldamers.

Photocatalytic reductive cyclizations of enones : Divergent reactivity of photogenerated radical and radical anion intermediates

Photocatalytic reactions of enones using metal polypyridyl complexes proceed by very different reaction manifolds in the presence of either Lewis or Brønsted acid additives. Previous work from our lab demonstrated that photocatalytic [2+2] cycloadditions of enones required the presence of a Lewis acidic co-catalyst, presumably to activate the enone and stabilize the key radical anion intermediate. On the other hand, Brønsted acid activators alter this reactivity and instead promote reductive cyclization reactions of a variety of aryl and aliphatic enones via a neutral radical intermediate. These two distinct reactive intermediates give rise to transformations differing in the connectivity, stereochemistry, and oxidation state of their products. In addition, this reductive coupling method introduces a novel approach to the tin-free generation of β-ketoradicals that react with high diastereoselectivity and with the high functional group compatibility typical of radical cyclization reactions.

Higher Manganese Silicide Nanowires of Nowotny Chimney Ladder Phase

We report the synthesis, structural identification, and electrical properties of the first one-dimensional (1-D) nanomaterials of a semiconducting higher manganese silicide (MnSi(2-x)) with widths down to 10 nm via chemical vapor deposition of the single-source precursor Mn(CO)(5)SiCl(3). The complex Nowotny chimney ladder structure of these homologous higher manganese silicides, also referred to as Mn(n)Si(2n-m), MnSi(1.75), or MnSi(1.8), contributes to the excellent thermoelectric performance of the bulk materials, which would be enhanced by phonon scattering due to 1-D nanoscale geometry. The morphology, structure, and composition of MnSi(2-x) nanowires and nanoribbons are examined using electron microscopy and X-ray spectroscopy. Elaborate select area electron diffraction analysis on single-crystal nanowires reveals the phase to be Mn(19)Si(33), one of a series of crystallographically distinct higher manganese silicides that have a Nowotny chimney ladder structure. Electrical transport study of single nanowires shows that they are degenerately doped with a low resistivity (17 mohms x cm) similar to the bulk.

Oxaziridine‐Mediated Oxyamination of Indoles: An Approach to 3‐Aminoindoles and Enantiomerically Enriched 3‐Aminopyrroloindolines

The pyrroloindoline natural products have attracted considerable interest both because of their biological activity and their unique structures (Figure 1). i Nature presumably produces these architecturally fascinating compounds via electrophilic cyclization cascades involving appropriately functionalized tryptamine and tryptophan precursors. In the laboratory, the use of chemical oxidants (e.g., m-CPBA, dioxirane, and NBS) to trigger similar cascades has been a common strategy for the total synthesis of these target molecules.ii Recently, several research groups have become interested in the synthesis of the subclass of pyrroloindoline alkaloids such as psychotrimine (1)iii and chaetomin (2)iv that feature a carbon-nitrogen bond at the C3 position of the oxidized indole.v However, only a limited number of methods for the direct electrophilic introduction of nitrogen at this position have been developed,vb,d,g,vi and thus the synthesis of aminated indole alkaloids remains a formidable synthetic challenge, especially in an enantioselective fashion.

STABILIZATION OF THE COLLAGEN TRIPLE HELIX BY O-METHYLATION OF HYDROXYPROLINE RESIDUES

The hydroxylation of proline residues in collagen is the most common posttranslational modification in humans. The hydroxylation is stereoselective, affording (2 S,4R)-4-hydroxyproline (Hyp) in the Yaa position of the canonical Xaa -Yaa-Gly triad and thereby bestowing marked stabilization upon the collagen triple helix.1 The means by which Hyp stabilizes collagen has engendered dispute. One hypothesis suggests that a network of water molecules links the Hyp hydroxyl groups and main-chain carbonyl groups. 2,3

n→π* interactions of amides and thioamides: implications for protein stability.

Carbonyl–carbonyl interactions between adjacent backbone amides have been implicated in the conformational stability of proteins. By combining experimental and computational approaches, we show that relevant amidic carbonyl groups associate through an n→π* donor–acceptor interaction with an energy of at least 0.27 kcal/mol. The n→π* interaction between two thioamides is 3-fold stronger than between two oxoamides due to increased overlap and reduced energy difference between the donor and acceptor orbitals. This result suggests that backbone thioamide incorporation could stabilize protein structures. Finally, we demonstrate that intimate carbonyl interactions are described more completely as donor–acceptor orbital interactions rather than dipole–dipole interactions.