Further studies in the acyl-type radical additions promoted by SmI2: mechanistic implications and stereoselective reduction of the keto-functionality

Attempts were made to promote the carbonyl coupling of cyclohexanone to 4-pyridylthioesters of N-carbamate-protected amino acids with the one electron reducing agent, samarium diiodide. Such reactions proved unsuccessful due to the inability of the ketyl-type radical anion intermediate to be reduced to the corresponding dianion at −78°C. Nevertheless, these results explain our recently published work on the high efficiency of the SmI₂-mediated acyl-type radical additions of the same thioesters with electron deficient alkenes [J. Am. Chem. Soc. 2003, 125, 4030]. A study was also undertaken to examine methods for the stereoselective reduction of N-carbamate-protected amino ketones to either the syn- or anti-vicinal amino alcohols. In most cases, LiAl(O-t-Bu)₃H and (S)-Alpine-Hydride were found to effectively provide the anti- and syn-amino alcohols, respectively. The SmI₂-promoted reduction of the same ketones afforded a majority of the syn-isomer with selectivities of approximately 5:1. However, in one case, the SmI₂-promoted reduction was found to be more effective than that of (S)-Alpine-Hydride.     

X-ray structures of new substituted 2-(pyrazol-1-yl)-2′-nitroacetanilides with pharmacological activity

The X-ray structures of four pharmacologically active lidocaine analogs, containing substituted pyrazole moieties as the basic residue and an o-nitrophenyl moiety as the hydrophobic residue, have been determined. They are 2-(pyrazol-1-yl)-2-nitroacetanilide (1), 2-(3,5-dimethyl-pyrazol-1-yl)-2-nitroacetanilide (2), 2-(3,5-dimethyl-4-iodo-pyrazol-1-yl)-2-nitroacetanilide (3), and 2-(3,5-dimethyl-4-nitro-pyrazol-1-yl)-2-nitroacetanilide (4). Crystal data are 1: space group Pn with a = 4.6944(1), b = 22.3890(3), c = 15.7481(2) Å, = 96.810(1)°, Z = 6; 2: P with a = 4.7277(2), b = 11.6878(5), c = 12.0355(6) Å, = 87.689(2), = 85.048(2), = 85.975(2)°, Z = 2; 3: I2/a with a = 24.108(5), b = 4.7321(9), c = 25.337(5) Å, = 96.09(3)°, Z = 8; 4: P2₁ with a = 5.7788(2), b = 8.9844(3), c = 14.0304(5) Å, = 101.611(1)°, Z = 2. Molecules of compound 1 adopt a unique, folded conformation stabilized by intramolecular hydrogen bonds and the crystal structure lacks significant intermolecular interactions. In contrast, molecules of 2–4 adopt common, extended conformations and their crystal structures are based on linear arrays of hydrogen bonded (N—H...O=C) molecules. Compound 3 displayed the highest local anesthetic activity while 2 was the most active in tests for anti-arrhythmic effects.     

Formation of a Highly Reactive Cobalt Nanocluster Crystal within a Highly Negatively Charged Porous Coordination Cage

Earth‐abundant first‐row transition‐metal nanoclusters (NCs) have been extensively investigated as catalysts. However, their catalytic activity is relatively low compared with noble metal NCs. Enhanced catalytic activity of cobalt NCs can be achieved by encapsulating Co NCs in soluble porous coordination cages (PCCs). Two cages, PCC‐2a and 2b, possess almost identical cavity in shape and size, while PCC‐2a has five times more net charges than PCC‐2b. Co²⁺ cations were accumulated in PCC‐2a and reduced to ultra‐small Co NCs in situ, while for PCC‐2b, only bulky Co particles were formed. As a result, Co NCs@PCC‐2a accomplished the highest catalytic activity in the hydrolysis of ammonium borane among all the first‐row transition‐metals NCs. Based on these results, it is envisioned that confining in the charged porous coordination cage could be a novel route for the synthesis of ultra‐small NCs with extraordinary properties.     

A Vastly Increased Chemical Variety of RNA Modifications Containing a Thioacetal Structure

Recently discovered new chemical entities in RNA modifications have involved surprising functional groups that enlarge the chemical space of RNA. Using LC‐MS, we found over 100 signals of RNA constituents that contained a ribose moiety in tRNAs from E. coli. Feeding experiments with variegated stable isotope labeled compounds identified 37 compounds that are new structures of RNA modifications. One structure was elucidated by deuterium exchange and high‐resolution mass spectrometry. The structure of msms²i⁶A (2‐methylthiomethylenethio‐N6‐isopentenyl‐adenosine) was confirmed by methione‐D3 feeding experiments and by synthesis of the nucleobase. The msms²i⁶A contains a thioacetal, shown in vitro to be biosynthetically derived from ms²i⁶A by the radical‐SAM enzyme MiaB. This enzyme performs thiomethylation, forming ms²i⁶A from i⁶A in a first turnover. The new thioacetal is formed by a second turnover. Along with the pool of 36 new modifications, this work describes a new layer of RNA modification chemistry.     

Asymmetric Synthesis of (R)‐1‐Alkyl‐Substituted Tetrahydro‐ß‐carbolines Catalyzed by Strictosidine Synthases

Stereoselective methods for the synthesis of tetrahydro‐ß‐carbolines are of significant interest due to the broad spectrum of biological activity of the target molecules. In the plant kingdom, strictosidine synthases catalyze the C?C coupling through a Pictet–Spengler reaction of tryptamine and secologanin to exclusively form the (S)‐configured tetrahydro‐ß‐carboline (S)‐strictosidine. Investigating the biocatalytic Pictet–Spengler reaction of tryptamine with small‐molecular‐weight aliphatic aldehydes revealed that the strictosidine synthases give unexpectedly access to the (R)‐configured product. Developing an efficient expression method for the enzyme allowed the preparative transformation of various aldehydes, giving the products with up to >98 % ee. With this tool in hand, a chemoenzymatic two‐step synthesis of (R)‐harmicine was achieved, giving (R)‐harmicine in 67 % overall yield in optically pure form.     

A highly enantio- and diastereoselective 1,3-dimethylallylation of aldehydes

A highly enantio- and diastereoselective pentenylation of aldehydes is described. The homoallylic alcohol derived from 1,3-dimethylallylation of (-)-menthone undergoes an efficient allyl-transfer reaction with a wide range of aliphatic aldehydes in the presence of an acid catalyst to give rise to the corresponding 4-methyl-2(E)-penten-4-yl-5-ol products in good yields with high enantio- and 4,5-syn-selectivities.     

Stereochemistry of nucleophilic attack by amine on a cationic π-allylnickel complex

Reaction of the π-allylnickel complex $\text{3}$ with morpholine gave a 1:1 mixture of the amines $\text{4}$ and $\text{5}$ indicating that the amine has attacked the π-allyl moiety from the side trans to nickel.     

Structural and chemical characterization of monofluoro-substituted oligo(phenylene-ethynylene) thiolate self-assembled monolayers on gold

Monolayers of oligo(phenylene-ethynylene) (OPE) molecules have exhibited promise in molecular electronic test structures. This paper discusses films formed from a novel molecule within this class, 2-fluoro-4-phenylethynyl-1-[(4-acetylthio)phenylethynyl]benzene (F-OPE). The conditions of self-assembled monolayer (SAM) formation were systematically altered to fabricate reproducible high-quality molecular monolayers from the acetate-protected F-OPE molecule. Detailed characterization of the F-OPE monolayers was performed by using an array of surface probes, including reflection absorbance infrared spectroscopy (RAIRS), contact angle (CA) measurements, spectroscopic ellipsometry (SE), X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS), and atomic force microscopy (AFM). XPS and RAIRS established that the SAM formed without removal of the F substituent and without oxidation of the thiol. The monolayer thickness, determined from SE and AFM based nanolithography, was consistent with the formation of a densely packed monolayer. The valence electronic structure of the SAM was consistent with an aromatic structure shifted by the electron-withdrawing fluorine substituent and intermolecular coupling within an oriented array of molecules.     

Cyclopropane structural units from homoaldol adducts

[reaction: see text] An efficient two-step homologation of aldehydes to cyclopropylaldehydes has been developed. Activation of homoaldol adducts derived from O-enecarbamates and N-enecarbamates provided high yields of cyclopropylaldehydes with good to excellent levels of trans/cis selectivity. Trapping of the intermediate oxonium ion and iminium ion intermediates has also been demonstrated, leading to direct isolation of cyclopropyl carbinol and cyclopropylamine products.     

Elektrochemische untersuchung von bis(diphenyldithiophosphin) disulfid

The electrochemical behaviour of bis(diphenyldithiophosphine)disulphide (RSSR) and mercuric diphenyldithiophosphinate [(RS)₂Hg] in ethanol-lithium perchlorate and ethanol-sulphuric acid media was studied by the methods of classical polarography, and electrolysis at controlled-potential and at a rotating disc platinum electrode. The data obtained show that RSSR is not reduced directly on the dropping mercury electrode but is adsorbed. It then undergoes a rapid chemical reaction causing the formation of (RS)₂Hg, which is electroactive. The electrolysis at controlled potential proves that (RS)₂Hg undergoes a two-electron reduction, giving diphenyldithiophosphinic acid (RSH) as a main product, whereas the oxidation of RSH leads to the production of (RS)₂Hg. Regardless of the fact that the chemical and adsorption equilibria during reduction of RSSR and (RS)₂Hg are complex, the coulometric generation of RSH is not difficult to achieve, and permits the use of RSSR as a coulometric reagent.