Synthesis of bis-(3,5)pyrazolophanes via double cycloadditive macrocyclisation

Double cycloadditive macrocyclisation of bis-hydrazonoyl chlorides 5 were performed with bis-allyl ethers 9 and 10, bis-vinyl ether 14 and bis-propargyl ether 18. The title compounds having a 18-, 19-, 22- or 24- membered ring annulated to the pyrazole units were obtained with good overall yield.     

Metal-Free and NBS-Mediated Direct Thiol-Disulfide Exchange Reaction to Access Unsymmetrical Disulfides

A metal-free and N-Bromosuccinimide (NBS)-mediated direct thiol-disulfide exchange reaction at room temperature is developed. A variety of unsymmetrical disulfides have been prepared with good to excellent yields. Efficient late-stage modification of amino acids and drugs demonstrates the utility of this strategy. In addition, easy to operate, broad substrate scope and good functional group tolerance further demonstrate that this reaction provides an essential complementary route to access unsymmetrical disulfides.     

Rolf Huisgen,Eminent Chemist and Polymath (1920–2020): In His Own Words and In His Publication Metrics

As a compliment to several other publications that present and honor Rolf Huisgen's research achievements, the first part of this paper reveals the human side of this eminent chemist. From excerpts from many of his personal and professional writings, Huisgen's personality and philosophies of life are revealed. Also revealed is Huisgen functioning as a historian of chemistry. The second part of this paper examines the scientometrics of Huisgen's publication history. In the late 1950s and early 1960s, Huisgen's career experienced a major transition in terms of publication metrics and the influence these papers had on the organic chemistry community. This was the result of his research into 1,3‐dipolar cycloadditions. Citations to his scientific contributions are well spread over many of his papers, demonstrating his constant work and the building up of a research topic, which continued after his official retirement in 1988. In fact, 17 % of his more than 600 publications appeared after 1988. The majority of Huisgen's papers were co‐authored with his many graduate and postdoctoral students. Consistent with the trend of that era, Huisgen was the sole author of most of his Review articles, and not just those of his many plenary lectures, and it is those Review articles that proved to be his most cited publications. This demonstrates the power and influence of Review articles—secondary sources, in the vocabulary of historians and sociologists of science. In those Review articles, Huisgen principally described the state of the art of 1,3‐dipolar cycloadditions—his golden offspring.     

Electrocyclic Ring-Opening of 1,2,4-Oxadiazole[4,5-a]piridinium Chloride: a New Route to 1,2,4-Oxadiazole Dienamino Compounds

1,2,4-Oxadiazole[4,5-a]piridinium chloride adds nucleophiles to undergo electrocyclic ring opening affording 1,2,4-oxadiazole dienamino derivatives. These pyridinium salts represent a special class of Zincke salts that are prone to rearrange when treated with primary amines or in the presence of bicarbonate to give the pyridones. The pivotal tuning of the experimental conditions leads to a straightforward synthesis of valuable 1,2,4-oxadiazole dienamine derivatives. The mechanism is also discussed in the light of NMR experiments and theoretical calculations.     

Synthesis of Isoxazole Conjugates of 1,4-Benzodioxane Moiety via Intermolecular 1,3-Dipolar Cycloaddition

1,3-Dipolar cycloaddition was utilized as a tool to conjugate the 1,4-benzodioxane moiety with several biologically active compounds such as steroid, sugar, and other aromatic scaffolds via isoxazole or triazole bridge. The propynyl ether of 2-hydroxymethyl-1,4-benzodioxane underwent 1,3-dipolar cycloadditions smoothly with different in situ generated nitrile oxides in good yields. The triazole conjugate of 1,4-benzodioxane was synthesized via click chemistry.     

Reactions of 1,2,4-Oxadiazole[4,5-a]piridinium Salts with Alcohols: the Synthesis of Alkoxybutadienyl 1,2,4-Oxadiazoles

1,2,4-Oxadiazole[4,5-a]piridinium salts add alcohols and alkoxides to undergo electrocyclic ring opening affording alkoxybutadienyl 1,2,4-oxadiazole derivatives. The pyridinium salts represent a special class of Zincke salts that are prone to rearrange to give alkoxybutadienyl 1,2,4-oxadiazoles when treated with suitable nucleophiles or, alternatively, to give pyridones in the presence of bicarbonate. The pivotal tuning of the experimental conditions leads to a straightforward synthesis of valuable 1,2,4-oxadiazole derivatives. The mechanism is also discussed in the light of previous observations.     

区域选择性合成三芳基取代的含氟吡唑

本文报道了碱促进下的三氟甲基取代炔与原位生成的腈亚胺的[1,3]-偶极环加成反应。该反应具有操作简单、条件温和、官能团兼容性好的特点,能以良好的产率和优异的区域选择性得到含有三氟甲基取代的吡唑杂环化合物。目标产物结构均经过1H NMR、13C NMR、19F NMR、HRMS等确证。该反应有望在生物活性分子合成中得到应用。     

Redox Transformation of Adducts from Cycloaddition of Diazoacetic Ester to β-Arylacryloyloxiranes

It was established that, in addition to ethyl 4-aryl-3-(2,3-epoxyalkanoyl)-4,5-dihydro-1H-pyrazole-5-carboxylates, the reaction of diazoacetic ester with β-arylacryloyloxiranes also gives ethyl 4-aryl-3(5)-(3-hydroxy-2-methylalkanoyl)-1H-pyrazole-5(3)-carboxylates. The latter are formed from the tautomeric ethyl 4-aryl-5-(2,3-epoxyalkanoyl)-4,5-dihydro-1H-pyrazole-3-carboxylates as a result of intramolecular oxidative-reductive disproportionation. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1150–1160, August, 2005.     

Assessment of mechanistic hypotheses of 1,3-dipolar cycloaddition of (arylsulfonyl)allene to nitrilimines by DFT reactivity indices

The mechanism of 1,3-dipolar cycloaddition between 1-[2-(acetylamino)phenylsulfonyl]-1,2-propadiene 1 and a series of N-(4-substituted)phenyl-C-methoxycarbonylnitrilimines 2 has been reinvestigated on the basis of DFT calculations and a quantitative formulation of the HSAB principle. Comparison of the new computational results with experimental findings led to the formulation of a mechanistic scheme involving both 1,3-prototropic and 1,3-arylsulfonyl shifts. The role of silver cation is also pointed out.     

1,3-偶极环加成合成双-1,2,4-噁二唑啉衍生物及单晶结构

2-苯基-1,2,3-三唑基-4-甲醛与1,3-丙二胺或对苯二胺缩合, 形成新的双席夫碱3和4, 然后分别与氯代肟在三乙胺条件下发生1,3-偶极环加成, 得到新型双-1,2,4-噁二唑衍生物6a～6f和7a～7f. 结构经元素分析, IR, 1H NMR和MS确证, 并用X射线衍射法测定了化合物6e的晶体结构. 化合物6e属于单斜晶系, C2/c空间群, 晶胞参数 a＝3.5134(8) nm, b＝0.50575(11) nm, c＝2.0598(5) nm, α＝90°, β＝102.02(8)°, γ＝90°, Mr＝756.81, V＝3.5798(14) nm3, Dc＝1.404 g/cm3, Z＝4, F(000)＝1576, μ＝0.095 mm－1, R＝0.0787, wR＝0.2093.     

Electro‐Oxidative S−H/S−H Cross‐Coupling with Hydrogen Evolution: Facile Access to Unsymmetrical Disulfides

Sulfur is an essential element because it exists widely in proteins. The disulfide bond is an important moiety in many different types of significant organic molecules. A new approach for oxidant‐ and catalyst‐free S?H/S?H cross‐coupling, with hydrogen evolution, to construct unsymmetrical disulfides was developed. Under the conditions of an undivided cell at room temperature, a series of unsymmetrical disulfides were prepared with up to 87 % yield from the direct coupling of an aryl mercaptan and alkyl mercaptan. Gram‐scale synthesis also highlights the synthetic utility of this electrochemical strategy.     

Mechanochemical Strecker Reaction: Access to α‐Aminonitriles and Tetrahydroisoquinolines under Ball‐Milling Conditions

A mechanochemical version of the Strecker reaction for the synthesis of α‐aminonitriles was developed. The milling of aldehydes, amines, and potassium cyanide in the presence of SiO₂ gave the corresponding α‐aminonitriles in good to high yields. The high efficiency of the mechanochemical Strecker‐type multicomponent reaction allowed the one‐pot synthesis of tetrahydroisoquinolines after a subsequent internal N‐alkylation reaction.     

Regiocontrolled Gold‐Catalyzed [2+2+2] Cycloadditions of Ynamides with Two Discrete Nitriles to Construct 4‐Aminopyrimidine Cores

Reported herein is the novel gold‐catalyzed intermolecular [2+2+2] cycloaddition of ynamides with two discrete nitriles to form monomeric 4‐aminopyrimidines, which are pharmaceutically important structural motifs. The utility of this new cycloaddition is demonstrated by the excellent regioselectivity obtained using a variety of ynamides and nitriles.     

Construction of Chiral Tri‐ and Tetra‐Arylmethanes Bearing Quaternary Carbon Centers: Copper‐Catalyzed Enantioselective Propargylation of Indoles with Propargylic Esters

Copper‐catalyzed enantioselective propargylation of indoles with propargylic esters and sequential Huisgen cycloaddition with azides lead to the construction of chiral triarylmethanes, bearing a quaternary carbon center, with high to excellent enantioselectivities. The result described herein can be used in the enantioselective preparation of a tetraarylmethane.     

Enantioselective 1,3-Dipolar [6+4] Cycloaddition of Pyrylium Ions and Fulvenes towards Cyclooctanoids

Organocatalytic enantioselective 1,3-dipolar [6+4] cycloadditions of pyrylium ion intermediates with fulvenes promoted by a chiral primary amine catalyst have been developed to proceed in moderate to good yields and high enantioselectivities. The resultant chiral bicyclo[6.3.0]undecane scaffold containing a transannular bridging ether is densely functionalised providing a rigid scaffold for further manipulations. Computational studies give important insights into the role of the primary amine catalyst. Analysis of the reaction shows that the catalytic reaction proceeds in a step-wise manner and rationalises the stereochemical outcome of the reaction. Several stereoselective complexity-generating transformations, facilitated by the diverse functional groups and transannular bridge, are presented, highlighting the versatility of the core towards a number of the cyclooctanoid natural products.     

Mechanochemical Activation of Zinc and Application to Negishi Cross‐Coupling

A form independent activation of zinc, concomitant generation of organozinc species and engagement in a Negishi cross‐coupling reaction via mechanochemical methods is reported. The reported method exhibits a broad substrate scope for both C(sp³)–C(sp²) and C(sp²)–C(sp²) couplings and is tolerant to many important functional groups. The method may offer broad reaching opportunities for the in situ generation organometallic compounds from base metals and their concomitant engagement in synthetic reactions via mechanochemical methods.     

Regio- and stereoselectivity of 1,3-dipolar cycloaddition of cyclic aldonitrones of the 3-imidazoline 3-oxide series to monosubstituted alkenes

Regio- and stereoselectivity of 1,3-dipolar cycloaddition of cyclic aldonitrones of the 3-imidazoline 3-oxide series mainly depends on the type of the substituent in the dipolarophile. The configuration of the main cycloadduct has been determined, and a method has been suggested to establish the stereochemistry of the cycloaddition products by¹H NMR spectroscopy. An increase in electron-acceptor properties of the substituent in the alkene molecule results in a decrease in the regio- and stereoselectivity of the cycloaddition.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 894–898, May, 1994.