Carbon-rich molecules: synthesis and isolation of aryl/heteroaryl terminal bis(butadiynes) (HC[triple bond]C-C[triple bond]C-Ar-C[triple bond]C-C[triple bond]CH) and their applications in the synthesis of oligo(arylenebutadiynylene) molecular wires

The synthesis, isolation and characterisation are reported for a series of terminal aryl/heteroaryl bis(butadiynes) (HC[triple bond]C-C[triple bond]C-Ar-C[triple bond]C-C[triple bond]CH) 4a-e including the X-ray molecular structure of the 2,5-pyridylene derivative 4d; compound 4a and the mono-protected analogue [HC[triple bond]C-C[triple bond]C-Ar-C[triple bond]C-C[triple bond]C-C(OH)Me2] 5a serve as convenient precursors for the synthesis of highly-conjugated oligo(arylenebutadiynylene)s.     

有机锡在不对称合成中的应用研究进展

金属有机化合物是不对称合成中常用的有机试剂。有机锡试剂易于制备，而且碳-锡键又易于断开，因此它们被广泛应用于有机合成中，当然也是不对称合成常用的试剂之一，是制备某些手性天然产物必备的试剂。由于锡的结构特点，它可以形成四配位、五配位甚至六配位的配合物，这些配合物作为路易斯酸可用作不对称合成中的催化剂、助催化剂。从已报道的文献看，大多数反应的产率及对映体选择性都在中等或中等以上水平，某些已达到了优良的水平。本文综述了有机锡作为反应试剂、催化剂、助催化剂在不对称合成中的应用。     

Enantioselective synthesis of (1E,3S)-1-iodoundec-1-en-5-yn-3-ol,the eicosanoid synthon

A synthesis of the title compound, the synthon for the constanolactones and other eicosanoids, has been developed from achiral starting compounds. The synthesis is based on the S-enantiodirected dihydroxylation of the double bond to introduce a chirality and on the use of conformational restriction of the triple bond (the latent Z-double bond) surroundings.     

Total synthesis of (+)-lithospermic acid by asymmetric intramolecular alkylation via catalytic C-H bond activation

The total synthesis of (+)-lithospermic acid is described. The efficient synthesis features an asymmetric alkylation via C-H bond activation to assemble the dihydrobenzofuran core of the natural product. This was accomplished via a chiral imine-directed C-H bond functionalization and represents the first application of this C-H activation method to natural product synthesis. Furthermore, a challenging deprotection of a late-stage permethylated lithospermic acid was achieved.     

Recent progress in copper nanocatalysis for sustainable transformations

Copper nanoparticles (CuNPs) have been deeply studied as catalyst for organic synthesis. Various new Cu nanocatalysts are reviewed for different types of organic reactions, such as C–C bond formation (including Mizoroki–Heck, Suzuki–Miyaura, Glaser-Hay coupling), C–N bond formation (including Chan-Lam, Buchwald–Hartwig, Ullmann and Goldberg coupling, alkyne–azide cycloaddition etc.), C–O bond formation and multi-step reactions with C–X (C, N, O) bond formation. Most CuNP-catalyzed protocols possess merits of mild reaction conditions, high catalytic efficiency, good functional group tolerance, lower cost, clean reaction profiles and reusable copper catalyst. The application of these CuNPs in organic synthesis holds potential for significant impact on advancing organic synthesis and promoting further development of organic copper chemistry.     

Gold‐Catalyzed [3+2]/Retro‐[3+2]/[3+2] Cycloaddition Cascade Reaction of N‐Alkoxyazomethine Ylides

A novel cascade reaction has been developed for the synthesis of 2,6‐methanopyrrolo[1,2‐b]isoxazoles based on the gold‐catalyzed generation of an N‐allyloxyazomethine ylide. This reaction involves sequential [3+2]/retro‐[3+2]/[3+2] cycloaddition reactions, thus providing facile access to fused and bridged heterocycles which would be otherwise difficult to prepare using existing synthetic methods. Notably, this reaction allows the efficient construction of three C−C bonds, one C−O bond, one C−N bond and one C−H bond, as well as the cleavage of one C−C bond, one C−O bond and one C−H bond in a single operation. The intermolecular cycloaddition of an N‐allyloxyazomethine ylide and the subsequent application of the product to the synthesis of tropenol is also described.     

基于2(5H)-呋喃酮的碳-杂成键反应研究进展

2(5H)-呋喃酮结构单元广泛存在于天然产物中,同时许多2(5H)-呋喃酮类化合物也是重要的有机合成中间体.因此,基于常见2(5H)-呋喃酮(1)的有机合成研究近年来引起了人们的关注.根据在有机合成反应中成键方式的不同,综述了在2(5H)-呋喃酮(1)环上形成C-O,C-N,C-S,C-P,C-Se,C-Si等碳-杂键的反应研究进展.     

Synthesis of new class of alkyl azarene pyridinium zwitterions via iodine mediated sp3 C-H bond activation

An efficient and conceptually different approach toward C-H bond activation by using iodine mediated sp(3) C-H functionalization for the synthesis of alkyl azaarene pyridinium zwitterions is described. This work has the interesting distinction of being the first synthesis of a new class of alkyl azaarene pyridinium zwitterion via transition-metal-free sp(3) C-H bond activation of an alkyl azaarene.     

Recent developments in natural product synthesis using metal-catalysed C-H bond functionalisation

Metal-catalysed C-H bond functionalisation has had a significant impact on how chemists make molecules. Translating the methodological developments to their use in the assembly of complex natural products is an important challenge for the continued advancement of chemical synthesis. In this tutorial review, we describe selected recent examples of how the metal-catalysed C-H bond functionalisation has been able to positively affect the synthesis of natural products.     

A Facile Entry to the Caffrane Skeletals : Formal Synthesis of Combretastatin D-2

Efficient synthesis of Combretastatin D-2, involving a selective reduction of a double bond over a triple bond and a high yielding Ullmann ether formation is described.     

Au-catalyzed synthesis of 5,6-dihydro-8H-indolizin-7-ones from N-(pent-2-en-4-ynyl)-beta-lactams

Au-catalyzed synthesis of 5,6-dihydro-8H-indolizin-7-ones from readily available N-(pent-2-en-4-ynyl)-beta-lactams is developed. In this reaction, a 5-exo-dig cyclization of the beta-lactam nitrogen to the Au-activated C-C triple bond is followed by heterolytic fragmentation of the amide bond, forming a highly nucleophilic acyl cation. An expedient formal synthesis of indolizidine 167B was easily achieved using this new method.     

Recent advances for the photoinduced C-C bond cleavage of cycloketone oximes

Nitriles are widely existed in many bioactive compounds, and they can be easily transformed into other functional groups. Therefore, the synthesis of nitriles under cyanide-free conditions is of significant importance. Recent advances for the synthesis of nitriles through photoinduced C-C bond cleavage of cycloketone oximes classified by the type of C-X bond forming are summarized. Various compounds possessing nitriles can be efficiently accessed via this method.     

糖缀合物的化学合成

本文介绍近年来各种糖缀合物化学合成的研究进展,包括各种糖苷键的化学合成方法以及各种特殊复杂糖缀合物,如糖肽、糖蛋白、糖脂的化学合成策略。     

The Enchanting Alkaloids of Yuzuriha

The oriental plant Yuzuriha (Daphniphyllum macropodum) elaborates a fascinating family of polycyclic, squalene-derived alkaloids that provide a test for state-of-the-art methods of organic synthesis. The intriguing structures of these natural products have inspired us to design and explore two rather different approaches for their laboratory synthesis. This article recounts and contrasts these two different syntheses. The first approach was based on a method of synthetic design that emphasizes efficient construction of the polycyclic skeleton of the molecule (Corey's “network analysis”). A strategic bond was identified and the synthesis planned around the late formation of this bond. The synthesis that was designed by this approach proceeded smoothly until the point where it was necessary to remove functional groups that had been incorporated solely for the purpose of forming the strategic bond. Although the problems were eventually overcome, the resulting synthesis was too long and did not control the configuration of one of the stereocenters. The second approach was based on a possible biosynthesis of one of the alkaloids and provided surprisingly easy access to the simpler members of the family. The success of this synthesis led to a concrete proposal about the biosynthesis of the alkaloids and to the discovery of the astonishing transformation depicted in Scheme 27. In this marvelous reaction, an acyclic squalene derivative is converted by successive treatment with ordinary commodity chemicals into a pentacyclic alkaloid. The transformation involves the formation of four carbon–carbon bonds, two carbon-nitrogen bonds, and one carbon-hydrogen bond!     

Palladium‐Mediated Direct Disulfide Bond Formation in Proteins Containing S‐Acetamidomethyl‐cysteine under Aqueous Conditions

One of the applied synthetic strategies for correct disulfide bond formation relies on the use of orthogonal Cys protecting groups. This approach requires purification before and after the deprotection steps, which prolongs the entire synthetic process and lowers the yield of the reaction. A major challenge in using this approach is to be able to apply one‐pot synthesis under mild conditions and aqueous media. In this study, we report the development of an approach for rapid disulfide bond formation by employing palladium chemistry and S‐acetamidomethyl‐cysteine [Cys(Acm)]. Oxidation of Cys(Acm) to the corresponding disulfide bond is achieved within minutes in a one‐pot operation by applying palladium and diethyldithiocarbamate. The utility of this reaction was demonstrated by the synthesis of the peptide oxytocin and the first total chemical synthesis of the protein thioredoxin‐1. Our investigation revealed a critical role of the Acm protecting group in the disulfide bond formation, apparently due to the generation of a disulfiram in the reaction pathway, which significantly assists the oxidation step.     

Influence of steric effects in solid-phase aza-peptide synthesis

Aza-peptides are peptide analogs with potential applications as drug candidates. However, due to difficulties associated with the synthesis of these compounds, information regarding their bioactivity is very limited. Herein, we identify steric hindrance as one reason for the slowness of the aza-peptide bond formation reaction. The steric effect of the side group of amino acids in their coupling with the semicarbazide moiety in the synthesis of a model peptide, H-AA-AzAla-Phe-NH₂, was studied and quantified using COMU as a coupling reagent. Characterization of the role of this structural factor in aza-peptide bond synthesis is essential for outlining a new and efficient synthesis protocol.     

Pseudosymmetry in azabicyclo[2.1.1]hexanes. A stereoselective construction of the bicyclic core of peduncularine

Intramolecular photocycloaddition of 41 or its equivalent leads to the formation of photoadduct 25. While retro-Mannich fragmentation of the "b" bond in 25 leads to the formation of 44 (via 43), with the incorrect relative stereochemistry for the synthesis of peduncularine 5, selective fragmentation of the "a" bond in 25 leads to the formation of 42 (via 26) with the correct relative stereochemistry for the synthesis of 5.     

The Rolling‐Up of Oligophenylenes to Nanographenes by a HF‐Zipping Approach

Intramolecular aryl–aryl coupling is the key transformation in the rational synthesis of nanographenes and nanoribbons. In this respect the C−F bond activation was shown to be a versatile alternative enabling the synthesis of several unique carbon‐based nanostructures. Herein we describe an unprecedentedly challenging transformation showing that the C−F bond activation by aluminum oxide allows highly effective domino‐like C−C bond formation. Despite the flexible nature of oligophenylene‐based precursors efficient regioselective zipping to the target nanostructures was achieved. We show that fluorine positions in the precursor structure unambiguously dictate the “running of the zipping‐program” which results in rolling‐up of linear oligophenylene chains around phenyl moieties yielding target nanographenes. The high efficiency of zipping makes this approach attractive for the synthesis of unsubstituted nanographenes which are difficult to obtain in pure form by other methods.     

Synthesis of Phenolic Compounds via Palladium Catalyzed C−H Functionalization of Arenes

Phenol and its derivatives are extremely useful compounds in organic synthesis, medicinal chemistry and material sciences. The synthesis of phenols involving selective construction of the C?O bond at a C?H bond of arenes using transition‐metal catalysis represents the most appealing strategy. Indeed, active research is currently going on for the synthesis of valuable phenolic compounds using a transition‐metal‐catalyzed C?H functionalization strategy. This short review summarizes recent advances on palladium‐catalyzed C?O bond forming reactions that enable direct access to phenolic compounds. These catalytic reactions proceed either via C?H esterification with trifluoroacetic acid/trifluoroacetic anhydride followed by in situ hydrolysis of the ester or via direct C?H hydroxylation. A brief analysis of substrate scope and limitation, reaction mechanism as well as synthetic utility of these reactions has been included.     

Oligonucleotides and nucleotidylpeptides. XXXII. Synthesis and hydrolytic stability of amino acid derivatives of adenosine 5′-di(tri)phosphates

The synthesis has been effected of the ethyl esters of adenosine-5′-diphospho-(P_β→N)-and adenosine-5′-triphospho(P_γ→N)-alanine. It has been shown that under the conditions of synthesis the serine analogues of ATP and ADP decompose. An investigation of the hydrolytic stability of the compounds synthesized has shown that they are unstable in acid and alkaline media. In an acid medium the phosphoramide bond is cleaved more rapidly than the phosphoric anhydride bond (in the case of the ADP analogue), while in an alkaline medium the ester bond is saponified and the phosphoric anhydride bond is cleaved. The ATP analogue is more labile both in acid and in alkaline media.