Complete stereocontrol in organocatalytic additions of β-ketosulfoxides to conjugated aldehydes

The use of β-ketosulfoxides as nucleophiles in reactions with α,β-unsaturated aldehydes catalyzed by proline derivatives allows complete control of configuration at the two chiral centers that are created during 1,4-addition reactions. The sulfinyl group can be used to create additional chiral centers in the resulting compounds and then removed while preserving the chirality of the carbon joined to the sulfur. The catalyst and the sulfinyl group are mainly responsible for the configurational control of the carbon atoms acting as electrophile and nucleophile, respectively, which allows the preparation of the four possible diastereoisomers in optically pure form. Theoretical calculations of the possible chiral nucleophilic species bearing diastereotopic faces allow us to postulate, for the first time, that enolates, instead of enols, are the active reagents in these reactions.     

On the Conformation of a Sterically Congested Amide Group in the Crystalline State and in Solution

The conformation in the crystalline state and in solution of the sterically congested tetramethylpiperidinederived amide group of the symmetric diamide I formed from 2,2,6,6-tetramethylpiperidine ( b ) and 1,2,5-thiadiazole-3,4-dicarbonyl dichloride ( c ), and of the mixed diamide II derived from b , c , and piperidine ( a ) has been investigated. In crystals, as observed with II , this group is strongly bent out-of-plane at both the N-atom and the carbonyl C-atom, and there is also a sizable twisting around the amide bond. Furthermore, the amide bond is abnormally long (1.37 Å). In CD₂Cl₂ (or CDCl₃) solution, the group is apparently planar in its ground-state conformation, but the energy barrier to rotation around the amide bond is low. This conclusion is based on low-temperature ¹H-NMR measurements on I , II , and on the symmetric diamide III derived from a and c .     

Crystal and molecular structure of cyclic sulfoxides: 2-cyano-2-ethoxycarbonyl-3,6-dihydro-4,5-dimethyl-2H-thiapyran 1-oxide and 2-phenyl-2-methoxycarbonyl-3,6-dihydro-2H-thiapyran 1-oxide

Crystal and molecular structures of the title compounds 1b and 1c have been determined by the X-ray method. Crystals of 1b are monoclinic, space group P2₁/c, and crystals of 1c are orthorhombic, space group P2₁2₁2₁. The sulfinyl oxygen atom and the alkoxycarbonyl group in both compounds are trans oriented, and the six-membered rings adopt a sofa conformation. The differences between conformation, bond lengths, and angles in the compounds investigated are discussed. © John Wiley & Sons, Inc.     

Rhodium-Catalyzed ortho-Bromination of O-Phenyl Carbamates Accelerated by a Secondary Amide-Pendant Cyclopentadienyl Ligand

It has been established that a newly developed cyclopentadienyl rhodium(III) [Cp^ARh^III] complex, bearing an acidic secondary amide moiety on the Cp ring, is able to catalyze the ortho-bromination of O-phenyl carbamates with N-bromosuccinimide (NBS) at room temperature. The presence of the acidic secondary amide moiety on the Cp^A ligand accelerates the bromination by the hydrogen bond between the acidic NH group of the Cp^A ligand and the carbonyl group of NBS.     

Coexistence of hydrogen-bonded loop and extended tetrapeptide conformations

The conformations of a protected tetrathiopeptide have been analysed by isotope labelling and two-dimensional infrared spectroscopy (2D-IR). It has been found that Boc-Ala-Gly(=S)-Ala-Aib-OMe in acetonitrile, as well as its oxopeptide analogue, can adopt a hydrogen-bonded loop conformation in coexistence with less restricted structures. The two types of conformations interconvert too quickly to be resolved on the nuclear magnetic resonance (NMR) timescale, but give rise to different cross peaks in two-dimensional infrared spectra. The hydrogen bond between the Boc terminal group and the amide proton of Aib can be broken by photoisomerisation of the thioamide bond.     

Molekül- und Kristallstruktur des Dimeren Magnesium-bis[bis(trimethylsilyl)amids]

Molecular and Crystal Structure of the dimeric Magnesium bis[bis(trimethylsilyl)-amide] The magnesium bis[bis(trimethylsilyl)amide] crystallizes as a dimeric molecule in the space group C2/c with {a = 1821.0(4); b = 1494.4(4); c = 1859.6(6) pm; β = 121.10(2)°; Z = 4 dimers}. The cyclic planar Mg₂N₂ moiety shows endocyclic NMgN angles of 95.8°. The bond lengths within this ring system to the four-coordinate, bridging nitrogen atoms N^b are 215 pm, whereas the distances between the magnesium atom and the terminal, three-coordinate nitrogen atom N^t display values of approximately 198 pm. These different coordination numbers of the nitrogen atoms affect the NSi bond length (N^tSi 171, N^bSi 177 pm).     

Boron Arylations of Subporphyrins with Aryl Zinc Reagents

Boron arylations of B‐(methoxo)triphenylsubporphyrin have been developed with a combined use of ArZnI?LiCl and trimethylsilyl chloride. Aryl zinc reagents bearing bromo, cyano, amide, and ester groups can be employed for the B‐arylation reaction to provide the corresponding B‐arylated subporphyrins in moderate yields. Postmodifications of B‐arylated subporphyrins have been demonstrated without loss of the B?C bond. These modifications include conversion of the cyano group into a benzoyl group with PhMgBr, hydrolysis of the ester group to give B‐(4‐carboxyphenyl)subporphyrin, and Pd‐catalyzed Suzuki–Miyaura coupling of the 4‐bromophenyl group to give a 1,4‐phenylene‐bridged subporphyrin–Zn^II porphyrin hybrid that displays intramolecular excitation energy transfer from the subporphyrin to the porphyrin. The newly synthesized B‐arylated subporphyrins have been fully characterized by NMR, UV/Vis absorption and fluorescence spectroscopies, mass spectrometry, electrochemical measurements, and X‐ray diffraction analysis.     

Modulations in restricted amide rotation by steric induced conformational trapping

The rotation around the amide bond in N,N-diethyl-m-toluamide (m-DEET) has been studied extensively and often used in laboratory instructions to demonstrate the phenomenon of chemical exchange. Herein, we show that a simple modification to N,N-diethyl-o-toluamide (o-DEET) significantly alters the dynamics of the restricted rotation around the amide bond due to steric interactions between the ring methyl group and the two N-ethyl groups. This alters the classic two-site exchange due to restricted rotation around the amide bond, to a three-site exchange, with the third conformation trapped at a higher-energy state compared to the other two. This often overlooked phenomenon is elucidated using variable-temperature NMR, two-dimensional exchange spectroscopy and molecular modeling studies.     

Kinetics and equilibria of cis/trans isomerization of backbone amide bonds in peptoids

The biological activities of N-substituted glycine oligomers (peptoids) have been the subject of extensive research. As compared to peptides, both the cis and trans conformations of the backbone amide bonds of peptoids can be significantly populated. Thus, peptoids are mixtures of configurational isomers, with the number of isomers increasing by a factor of 2 with each additional monomer residue. Here we report the results of a study of the kinetics and equilibria of cis/trans isomerization of the amide bonds of N-acetylated peptoid monomers, dipeptoids, and tripeptoids by NMR spectroscopy. Resonance intensities indicate the cis conformation of the backbone amide bonds of the peptoids studied is more populated than is generally the case for the analogous secondary amide bond to proline residues in acyclic peptides. Rate constants were measured by inversion-magnetization transfer techniques over a range of temperatures, and activation parameters were derived from the temperature dependence of the rate constants. The rate of cis/trans isomerization by rotation around the amide bonds in the peptoids studied is generally slower than that around amide bonds to proline residues and takes place on the NMR inversion-magnetization transfer time scale only by rotation around the amide bond to the C-terminal peptoid residue.     

Synthesis and Structure of a Cp^＊Ir Half-sandwich Complex Containing Azido and Bis（diphenylthiophosphoryl）amide Ligands

The title complex [CpIr{N(Ph2PS)2}(N3)](N(Ph2PS)2=bis(diphenylthiophosphoryl)amide,Cp=pentamethylcyclopentadienyl) has been prepared and characterized by X-ray diffraction analysis.It crystallizes in monoclinic,space group P21/n with a=11.6946(1),b=18.9273(2),c=15.7859(1),β=105.731(1)°,V=3363.29(5)3,Z=4,Mr=817.92,Dc=1.615g/cm3,μ(MoKα)=4.219 mm-1,F(000)=1624,S=1.028,the final R=0.0355 and wR=0.0848 for 5987 observed reflections with Ⅰ 2σ(Ⅰ) and 363 variables.The molecular structure of 1 consists of discrete monomeric molecule with a distorted octahedral configuration around the iridium atom,having a Cp ring at one face and bonded with a chelating bis(diphenylthiophosphoryl)amide group as well as a terminal azido ligand.The average Ir-S and Ir-N bond lengths are 2.416(1) and 2.121(5),respectively.     

Structural aspects of metal–amide complexes

An exhaustive survey of crystal structure data on simple amides and metal complexes containing monodentate amide ligands has been performed. Statistical analysis of structural features are reported as a function of the degree of alkylation of the amide functional group, the type of metal ion in the amide complex, and the type of binding to the metal ion. Average values are reported for bond lengths, bond angles, and torsional angles. Orientational preferences of the coordinated amide ligand are discussed in terms of M–O–C bond angles and M–O–C–N torsion angles.     

Inherent Conformational Preferences of Ac‐Gln‐Gln‐NHBn: Sidechain Hydrogen Bonding Supports a β‐Turn in the Gas Phase

Gas‐phase single‐conformation spectroscopy is used to study Ac‐Gln‐Gln‐NHBn in order to probe the interplay between sidechain hydrogen bonding and backbone conformational preferences. This small, amide‐rich peptide offers many possibilities for backbone–backbone, sidechain–backbone, and sidechain–sidechain interactions. The major conformer observed experimentally features a type‐I β‐turn with a canonical 10‐membered ring C=O—H?N hydrogen bond between backbone amide groups. In addition, the C=O group of each Gln sidechain participates in a seven‐membered ring hydrogen bond with the backbone NH of the same residue. Thus, sidechain hydrogen‐bonding potential is satisfied in a manner that is consistent with and stabilizes the β‐turn secondary structure. This turn‐forming propensity may be relevant to pathogenic amyloid formation by polyglutamine segments in human proteins.     

Gas-Phase Peptide Sulfinyl Radical Ions: Formation and Unimolecular Dissociation

A variety of peptide sulfinyl radical (RSO?) ions with a well-defined radical site at the cysteine side chain were formed at atmospheric pressure (AP), sampled into a mass spectrometer, and investigated via collision-induced dissociation (CID). The radical ion formation was based on AP reactions between oxidative radicals and peptide ions containing single inter-chain disulfide bond or free thiol group generated from nanoelectrospray ionization (nanoESI). The radical induced reactions allowed large flexibility in forming peptide radical ions independent of ion polarity (protonated or deprotonated) or charge state (singly or multiply charged). More than 20 peptide sulfinyl radical ions in either positive or negative ion mode were subjected to low energy collisional activation on a triple-quadrupole/linear ion trap mass spectrometer. The competition between radical- and charge-directed fragmentation pathways was largely affected by the presence of mobile protons. For peptide sulfinyl radical ions with reduced proton mobility (i.e., singly protonated, containing basic amino acid residues), loss of 62?Da (CH₂SO), a radical-initiated dissociation channel, was dominant. For systems with mobile protons, this channel was suppressed, while charge-directed amide bond cleavages were preferred. The polarity of charge was found to significantly alter the radical-initiated dissociation channels, which might be related to the difference in stability of the product ions in different ion charge polarities.     

Desymmetrization of cyclohexa-2,5-dienes through a diastereoselective protonation-hydroamination cascade

[reaction: see text] Intramolecular hydroamination of cyclohexa-2,5-dienes led with high selectivity to the corresponding bicyclic allylic amines. This study demonstrates that the reaction does not proceed through a direct hydroamination of one of the diastereotopic olefins but more likely involves a diastereoselective protonation of a pentadienyl anion, followed by addition of a lithium amide across the double bond of the resulting 1,3-diene, and is concluded by a highly regioselective protonation of the final allylic anion.     

Ab initio studies of structural features not easily amenable to experiment: Part 6. Quantitative estimate of the effect of bond delocalization on structure and hyperconjugative interaction of the amide group

The structural changes, which occur in the amide unit when the NH₂-group is twisted out of plane by rotation about the NC bond, have been determined by comparing the completely relaxed ab initio geometries of planar and perpendicular formamide and acetamide. In the perpendicular conformation, in which the π-electron amide resonance is uncoupled, the NC bond distance is 0.080.09 Å longer than in the planar form; the CO bond distance is about 0.01 Å shorter; NH distances are about 0.01 Å longer; and HNC angles are 510° smaller, whereas the CNO angle is relatively constant. Because of the apparent invariance of CH₃-hyperconjugation effects in planar and perpendicular acetamide, it is tentatively postulated that anomeric orbital interactive effects (involving the lone pair on NH, the CO π-electron pair and antibonding π*-group-orbitals on C(α) in NHC(HR)C(O)), which should be an important factor in determining peptide chain conformation, do not vary significantly with small deviations from amide group planarity.     

Structural characterization of synthetic poly(ester amide) from sebacic acid and 4-amino-1-butanol by matrix-assisted laser desorption ionization time-of-flight/time-of-flight tandem mass spectrometry

Matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS/MS) was employed to analyze a poly(ester amide) sample (PEA-Bu) from the melt condensation of sebacic acid and 4-amino-1-butanol. In particular, we investigated the fragmentation pathways, the ester/amide bond sequences and the structure of species derived from side reactions during the synthesis. MALDI-TOF/TOF-MS/MS analysis was performed on cyclic species and linear oligomers terminated by dicarboxyl groups, carboxyl and hydroxyl groups and diamino alcohol groups. The sodium adducts of these oligomers were selected as precursor ions. Different end groups do not influence the fragmentation of sodiated poly(ester amide) oligomers and similar series of product ions were observed in the MALDI-TOF/TOF-MS/MS spectra. According to the structures of the most abundant product ions identified, the main cleavages proceed through a beta-hydrogen-transfer rearrangement, leading to the selective scission of the --O--CH2-- bonds. Abundant product ions originating from --CH2--CH2-- (beta-gamma) bond cleavage in the sebacate moiety were also detected. Their formation should be promoted by the presence of an alpha,beta-unsaturated ester or amide end group. MALDI-TOF/TOF-MS/MS provided structural information concerning the ester/amide sequences in the polymer chains. In the MALDI-TOF/TOF-MS/MS spectra acquired, using argon as the collision gas, of cyclic species and linear oligomers terminated by diamino alcohol groups, product ions in the low-mass range, undetected in the mass spectra acquired using air as the collision gas, proved to be diagnostic and made it possible to establish the presence of random sequences of ester and amide bonds in the poly(ester amide) sample. Furthermore, MALDI-TOF/TOF-MS/MS provided useful information to clarify the structures of precursor ions derived from side reactions during the synthesis.     

Improving foldamer synthesis through protecting group induced unfolding of aromatic oligoamides

The hydrogen bond rigidified backbones of aromatic oligoamides are temporarily interrupted by replacing the amide hydrogens with the acid-labile 2,4-dimethoxybenzyl (DMB) group, which allows the efficient preparation of long folding oligomers that, upon removal of the DMB groups, fold into multiturn helices. [structure: see text]     

Palladium-catalyzed intramolecular allylic alkylation of α-sulfinyl carbanions: a new asymmetric route to enantiopure γ-lactams

Asymmetric intramolecular palladium-catalyzed allylic alkylation allowing access to disubstituted sulfinyl γ-lactams is described. The use of unsaturated amides bearing a sulfinyl group of defined absolute configuration together with enantiopure BINAP as the ligand in a biphasic medium provided good diastereoselectivities with clear solvent effect.     

Neutral cholic acid–coumarin conjugate exhibit excellent anion binding properties by cooperative aryl CH and amide NH segments

A neutral cholic acid–coumarin conjugate was developed for anion recognition. It is revealed by the experimental and theoretical results that the coumarin group can provide CH segments as hydrogen bond donors by cooperation with the adjoining amide NH segments. With excellent biocompatibility, this receptor with coumarin as fluorescence sensors also have the potential to be used as an efficient and non-destructive probe for anion detection in living cells. This work displays a new insight into the importance of coumarin group as anion recognition group, which is not well presented so far.