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An asymmetric synthesis of tetra-substituted cyclobutanes involving an organocatalytic, stepwise [2+2]-cycloaddition is described. The secondary-amine-catalyzed method allows for the hetero-dimerization of two different cinnamic-acid-derived sub-units, opening a novel one-step assembly to densely functionalized, head-to-tail coupled dimeric cyclobutanes in high enantiomeric excess. A series of selective synthetic interconversions in these sensitive cycloadducts is also described.

A total synthesis of the proposed structure of the natural macrolactone phomolide G (1) by a bidirectional strategy from L-tartaric acid is reported. The ω-terminus of the molecule was elaborated by nitrile extension, C3-alkylation and a substrate-controlled 1,3-ketone reduction. The α-terminus was extended by a C2 aldehyde-to-alkenal homologation followed by an auxiliary controlled aldol reaction. Macrolactonization and deprotection yielded compound 1 (confirmed by X-ray analysis). This putative structure of phomolide G displayed discordant NMR spectroscopic data in comparison with those of the natural product. Detailed inspection of all NMR spectroscopic data available indicated phomolide G to be likely a diastereomer of 1. The synthetic strategy developed allows control of the absolute stereochemistry at all four chiral secondary alcohol groups. Further manipulation allowed for the preparation of diastereomer 33, the 1H and 13C NMR spectroscopic data of which are in full accord with that reported for the natural product.

Interest in developing renewable fuels is continuing to grow and biomass represents a viable source of renewable carbon with which to replace fossil-based components in transportation fuels. During our own work, we noticed that chemists think in terms of functional groups whereas fuel engineers think in terms of physical fuel properties. In this Concept article, we discuss the effect of carbon and oxygen functional groups on potential fuel properties. This serves as a way of informing our own thinking and provides us with a basis with which to design and synthesize molecules from biomass that could provide useful transportation fuels.

Recent research in oxidation catalysis has focused on employing first-row metals with a lower environmental impact than their traditional counterparts. Iron is particularly suited for this task since the discovery of isolable non-heme iron(IV) complexes over a decade ago. This Letter summarizes the developments in the last decade for oxidation of organic substrates that proceed through iron(IV) intermediates. Eight separate oxidation reactions are reviewed.

Urea derivatives that contain a phenothiazine unit react with electron rich arenes in the presence of triflic anhydride to give the corresponding arenecarboxamides.

A new synthetic method has been developed for the synthesis of 2,4,5-substituted isoindolinones by means of intramolecular inverse-electron demand Diels–Alder cycloaddition reactions of substituted pyridazines. By taking advantage of the inherent reactivity of an intermediate chloropyridazine, a diverse set of analogues were prepared from common reagents and intermediates.

The structures, vibrational frequencies, and thermodynamic stabilities of the homonuclear polyhalogen ions, X3+, X3–, X4+, X4–, X5+, and X5– (X = Cl, Br, I), have been calculated at the CCSD(T) level. The energetics were calculated using the Feller–Peterson–Dixon approach for the prediction of reliable enthalpies of formation. The calculations allow the following predictions where stabilities are defined in terms of thermodynamic quantities. (1) The X3+ cations are stable toward loss of X2; (2) the X3– anions are marginally stable toward loss of X2 with Cl3– being the least stable; (3) the X4+ cations and X4– anions are only weakly bound dimers of X2+1/2 and X2–1/2 units, respectively, but the cations are marginally stable toward decomposition to X3+ and X, with I4+ having the lowest dissociation energy, whereas the X4– anions decompose spontaneously to X3– and X; (4) the X5+ cations are only marginally stable at low temperatures toward loss of X2, with Cl5+ being the least stable; and (5) the X5– anions ...

A subclass of metal-organic frameworks (MOFs) undergoes a “breathing” phenomenon which is a reversible flexing of the framework as a function of adsorbed guest. The existence of multiple stable states in a single framework leads to the modification of the shape and size of the pores as a function of guest, and has encouraged researchers to consider innovative applications for these flexible materials. To assist in improving the designs of these breathing MOFs, a thorough understanding of the different mechanisms by which frameworks breathe, must be established. This review will classify current breathing mechanisms by designating which part of the framework will not flex. By classifying the dimensional rigidity within a framework, a more in-depth discussion of each breathing mechanism can be established. Additionally, strategies for the design and synthesis of the next generation of breathing MOFs based on the reviewed research are discussed.

Methods for the cyclodehydration of N-(aminoalkyl)benzamides are few and employ harsh reaction conditions. We have found that the easily prepared phosphonium anhydrides 1 (Hendrickson reagent) or 2 can be used for cyclodehydration of N-(aminoalkyl)benzamides under very mild conditions (room temperature) to produce five-, six-, and seven-membered cyclic amidines. Good yields are obtained by employing a temporary trityl group protection strategy. Cyclic analogue 2 can be used when the product cyclic amidine is organic-soluble, thus producing water-soluble byproducts.

The direct synthesis of aziridines from alkenes and a nitrene source with the correct functionality on the nitrogen atom has remained an elusive goal in synthetic chemistry. Ruthenium, cobalt, and iron porphyrin complexes have been demonstrated to catalyze the formation of aziridines from electron-withdrawing aryl azides and a limited selection of conjugated alkenes. Our group is expanding the scope of catalytic aziridination to include electron-donating aryl azides and aliphatic alkenes through the use of a novel tetracarbene iron catalyst.

A series of title compounds is prepared and evaluated as potential bioreducible substrates for the enzymes NAD(P)H: quinone oxireductase 1 (NQO1) and Escherichia coli nitroreductase (NR).

While the “normal” cycloaddition between dienes and alkynes leads to formation of six-membered Diels—Alder or hetero-Diels—Alder ring products, the reductive cycloaddition using BEt3 as the active reducing agent and MeOH as the proton donor allows the synthesis of either cyclopentenols (from enals and alkynes) or cyclopentenones (from enoates and alkynes).

The new scaffold (IV), based on antitrypanosomal and antimalarial compounds isolated from different Plakortis species, contains a peroxide unit which is stable to chemical manipulation elsewhere in the molecule.

The crystal structures of [XeF][SbF6] (space group P21/c, Z = 4), [XeF][BiF6] (space group P21/c, Z = 4), and [XeF][Bi2F11] (space group P212121, Z = 4) are determined for the first time (single crystal XRD), and those of XeF2 (space group I4/mmm, Z = 2), [XeF][AsF6] (space group P21/n, Z = 4), [XeF][Sb2F11] (space group P21, Z = 2), and [XeF3][Sb2F11] (space group P, Z = 2) are redetermined with greater precision at -173 °C.

A synthesis of penems from azetidinone 1 is described in detail. This synthesis is used to prepare multikilo batches of (5R,6S)-2-[[-(carbamoyloxy)ethyl]thio]-6-[(R)-1-hydroxyethyl]penem-3-carboxylic acid (10), (Sch 34343). It is practical as all chemical steps progress in high yields, and isolation of all unstable intermediates is avoided. The eight step conversion of (3S,4R)-3-[(R)-1-hydroxyethyl]-4-triphenylmethylthio-2-azetidinone (1) to penem 10 via intermediacy of stable, solid (3S,4R)-1-[[(allyloxy)carbonyl]methyl]-3[(R)-hydroxyethyl]-4- (argentiothio)-2-azetidinone (4), and (3S,4R)-1-[[(allyloxy)carbonyl]methyl]-3- [(R)-1-hydroxyethyl]-4-β-naphthoxy (thiocarbonyl)thio-2-azetidinone (5) is achieved in 43% yield.

The pattern of reactions occurring between t- butoxy radicals and a number of cyclic alkenes has been investigated by the nitroxide radical-trapping technique. The major reaction pathway is allylic abstraction unless this position is at a bridgehead as in norbornene where the major pathway is radical addition. The technique is sufficiently sensitive to identify minor reaction pathways of non-allylic substitution and radical addition when in the presence of extensive allylic substitution. Some stereoselective effects are also detected.

A synthesis of 2-substituted-1,3-dienes is reported which uses silicon as a control element: Eight aldehydes were converted into α-silyl ketones by treatment with trimethylsilylmethylmagnesium chloride and rapid Collins oxidation. Addition of vinylmagnesium bromide to the resulting α-silyl ketones, followed by Peterson elimination, gave a series of dienes. The route was used to make (4S)-3-methylene-t-[(phenylmethoxy)methoxy]pent-1-ene from (–)-ethyl lactate; low asymmetric induction was observed in the Diels–Alder reactions of this diene with diethyl fumarate and N-phenylmaleimide.

The protection of a range of chiral alcohols with chloromethyl-(1R)-menthyl ether is reported. Conditions for the deprotection of (1R)-menthoxymethyl ethers are described which do not lead to racemisation of homochiral alcohols. The usefulness of the (1R)-menthoxymethyl ether group (MM) as a simple means of measuring enantiomeric excess in a reaction sequence starting from ethyl lactate is outlined.

A series of 2,6-bis(omega-aminoalkanamido)anthracene-9,10-diones (9,10-anthraquinones), of general formula Ar(NHCO(CH2)nNR2)2, where Ar = anthracene-9,10-dione and n = 1 or 2, have been synthesized by treatment of the corresponding bis(omega-haloalkanamido) derivatives with appropriate secondary amines. The DNA-binding properties of these compounds were evaluated by thermal denaturation studies, unwinding of closed-circular DNA, determination of association constants in solution, and examined by molecular modeling. A representative compound in the series has been examined by X-ray crystallography. In vitro cytotoxicity data is reported for the compounds and some indications of structure-activity relationships have been discerned. In particular, those compounds with two methylene links (n = 2) in each side chain separating the amide and terminal amine moieties have superior activity and, in general, enhanced DNA binding characteristics. It is postulated that the mode of reversible binding of these compounds to DNA involves the side chains occupying both major and minor grooves and, further, that this may confer cytotoxic properties which are distinct from those of previously reported anthracene-9,10-dione cytotoxins.

Farnesyl-Protein transferase catalyses a post-translational modification of Ras that is obligatory for the cell transforming activity of this oncogene protein. The screening of natural products to identify inhibitors of this enzyme as a potential anticancer agents, has led to the isolation of two novel dicarboxylic acids, named chaetomellic acids from Chaetomella acutiseta, as potent and selective inhibitors which appear to be the first examples of nonphosphorous containing FPP mimics.

(3S,5R)-N,3-Dibenzyl-3,4,5.6-tetrahydro-5-phenyl-1,4-oxazin-2-one, derived from L-phenylalanine and phenacyl bromide, was alkylated in a diastereoselective manner to give a range of α-alkylated phenylalanine derivatives.

The novel zaragozic acid C ( 1 ) has been isolated as a potent inhibitor of squalene synthase. It was found to be a competitive inhibitor of rat liver squalene synthase with an apparent K i of 45 ± 15 pM, and a broad spectrum antifungal agent against both yeast and filamentous fungi.

The direct formation of 2,2-disubstituted 1,3-cyclopentanedione compounds by a Lewis acid catalysed reaction with 1,2-bis(trimethylsilyloxy)cyclobutene proceeds in good to excellent yields with unhindered ketals, but steric hindrance reduces the yields considerably. A carbonyl group α or β to the ketal, or a carbon–carbon double bond α to the ketal, stops the reaction completely. Orthoesters do not give geminally acylated products in synthetically useful yields.

Two carbon-bridged analogues 11 and 15 of the potent microtubule inhibitor BW1069C85 (1) have been synthesised and evaluated for antitubulin and antitumour activity in vitro. Though the compounds were somewhat less potent than BW1069C85, significant activity against tubulin polymerisation and cell proliferation was demonstrated in the assays. Synthese von antitumor-wirksamen kohlenstoffverbruckten Imidazopyridazincarbamaten Es wurden die kohlenstoffverbruckten Analoga 11 und 15 des hochwirksamen Mikrotubulihemmers BW1069C85 (1) dargestellt und deren Antitubulinwirksamkeit und Antitumorwirksamkeit in vitro gepruft. Obwohl die Verbindungen in diesen Versuchen etwas schwacher als BW1069C85 wirken, wurde bedeutsame Wirksamkeit gegen Tubulinpolymerisierung und Zellwachstum gefunden.

Intramolecular Friedel–Crafts acylation of a pyrrole derived from L-glutamic acid, followed by a highly selective hydrogenation, leads to either of the optically pure indolizidine alkaloid precursors 6 or 7, depending on the catalyst.