Diastereoselective intramolecular SmI2-H2O-amine mediated couplings

The SmI2-H2O-amine mixture has been shown to be effective for intramolecular couplings providing diastereoselectivities of up to 100% de in the coupling of O-cyclohexenyliodophenol derivatives into heterocycles.     

Efficient palladium-catalyzed direct arylation of azines and diazines using ligand-free conditions

The use of the palladium-catalyzed direct arylation was successfully tested on different electron-deficient heterocycles. The results demonstrate the effectiveness of the method based on the intramolecular coupling reaction providing polyazacyclic systems. This new application was obtained by using ligand-free conditions with the mixture of Pd(OAc)₂ and TBAC as catalytic system. With suitable substrates different products arising from regioselective coupling were observed.     

Cyanide-catalyzed cyclizations via aldimine coupling

Aldimine coupling (AIC) is the nitrogen analogue of the benzoin condensation and has been applied to dialdimines, providing the first examples of cyclizations effected by cyanide-catalyzed AIC. Sodium cyanide promoted the facile, intramolecular cyclization of several dialdimines in N,N-dimethylformamide, methanol, or methylene chloride/water (phase-transfer conditions) yielding a variety of six-membered heterocycles. Under aerobic conditions, an oxidative cyclization occurs to provide the diimine heterocycle. Oligomerization was observed with rigid dialdimines for which cyclization was precluded.     

Intramolecular Coupling of Terminal Alkynes by Atom Manipulation

Glaser-like coupling of terminal alkynes by thermal activation is extensively used in on-surface chemistry. Here we demonstrate an intramolecular version of this reaction performed by atom manipulation. We used voltage pulses from the tip to trigger a Glaser-like coupling between terminal alkyne carbons within a custom-synthesized precursor molecule adsorbed on bilayer NaCl on Cu(111). Different conformations of the precursor molecule and the product were characterized by molecular structure elucidation with atomic force microscopy and orbital density mapping with scanning tunneling microscopy, accompanied by density functional theory calculations. We revealed partially dehydrogenated intermediates, providing insight into the reaction pathway.     

Intramolecular coupling of allyl carboxylates with allyl stannanes and allyl silanes: a new type of reductive elimination reaction?

The palladium-catalyzed intramolecular coupling of allyl stannanes with allyl carboxylates provides a general synthesis of five- and six-membered-ring carbocycles. The intramolecular coupling leads selectively to trans five-membered carbocycles and cis six-membered carbocycles, regardless of the cis or trans configuration of the allylic functions in the starting material. For example, the stereoselective synthesis of 10-epi-elemol demonstrated the cis configuration of the six-membered carbocycles. The related Oppolzer cyclization leads to lower yields, or fails completely, with substrates substituted at C-3 of the allyl and/or alkene terminus. The palladium-catalyzed intramolecular coupling of allyl silanes with allyl trifluoroacetates allows the synthesis of trans five-membered-ring carbocycles and requires the use of a bicyclic phosphite as the ligand. DFT calculations suggest that the preferred pathway for the intramolecular allyl/allyl coupling is by formation of the Cbond;C bond between the C-3 termini of the allyl ligands of bis(eta(3)-allyl)palladium complexes.     

Ketyl-allene cyclizations promoted by samarium(II) iodide

[reaction: see text] Samarium(II) iodide has proven to be an effective reagent for intramolecular reductive coupling reactions. Previous investigations of intramolecular ketyl-olefin coupling reactions provided carbocycles in excellent yield and good diastereoselectivity. This method has been extended to ketyl cyclizations with allenes. Substrates leading to both carbocycles and heterocycles in a selective manner are explored.     

Relationship between the Dynamic Properties of 1h Ice and Xenon Hydrate and the Interplay of Intramolecular and Intermolecular Vibrations

A new approach was used to simulate vibration spectra of 1h ice and xenon hydrate in the range 0–4000 cm^-1, which encompasses both intramolecular and intermolecular vibrations. This approach, based on the lattice dynamics method, enables full spectra to be obtained for molecular crystals with allowance for the coupling of intramolecular and lattice vibrations. It is shown that consideration of this coupling leads to splitting of the peaks of intramolecular vibrations and to a significant change in the spectrum in the range of translation and libration molecular vibrations, which agrees qualitatively with experimental results.     

Nickel-catalyzed reductive coupling of alkynes and epoxides

Nickel-catalyzed, intramolecular and intermolecular reductive coupling of alkynes and epoxides affords synthetically useful homoallylic alcohols of defined alkene geometry. Very high regioselectivity is generally observed, and cyclizations proceed with complete selectivity for endo epoxide opening. This catalytic reaction represents the first use of a non-pi-based electrophile in a growing class of nickel-catalyzed, multicomponent coupling reactions, and is the first catalytic method of reductive coupling of alkynes and epoxides that is effective for both intermolecular and intramolecular cases, and mechanistically distinct from these, possibly involving a nickella(II)oxetane.     

Synthetic studies on macroviracin A: a rapid construction of C(42) macrocyclic dilactone corresponding to the core

The C(2)-symmetric macrodiolide core 2 of an antiviral agent, macroviracin A (1), was constructed in a single step by the intermolecular macrodimerization of C(22)-hydroxy carboxylic acid 3 with 2-chloro-1,3-dimethylimidazolinium chloride and DMAP in the presence of sodium hydride (NaH). The use of potassium hydride instead of NaH caused the intramolecular cyclization, predominantly providing the corresponding monomer 26. The acid 3 was synthesized through a series of reactions such as the coupling reaction of acetylene 5 and oxirane 6, stereoselective glycosidation with the trichloroacetimidate method, and Jones oxidation.     

Sequential one-pot method for oxy-Michael addition,Heck coupling,and degradation followed by condensation: facile synthesis of 2-benzoxepin-3(1H)-ones

A sequential one-pot intermolecular oxy-Michael addition, intermolecular Heck coupling, and intramolecular degradation (retro-oxy-Michael addition) followed by condensation method has been developed for the synthesis of interesting 2-benzoxepin-3(1H)-ones. Significantly, the 2-benzoxepin-3(1H)-ones form the core quantum of biologically vital natural products. The initial oxy-Michael addition and Heck coupling steps involve a straight forward construction of C–O and C–C bonds, whereas, the final condensation step follows a novel mechanistic path via intramolecular degradation, double bond isomerization, and intramolecular condensation. Notably, a remarkable solvent effect has been observed in-order to promote the final intramolecular condensation.     

Intramolecular oxidative coupling of 3-indolylarylketones with Pd(II)-catalysis under air: convenient access to indenoindolones

A Pd-catalyzed method has been developed for the intramolecular oxidative coupling of 3-indolylarylketones under open air as terminal oxidant toward the synthesis of indeno[1,2-b]indol-10(5H)-ones. This reaction represents an intramolecular coupling with dual activation of C-H bonds for electron-deficient arenes, while such reactions are common for electron-rich arenes. Pd(II)-catalysis with pivalic acid as co-catalyst has been found to be crucial. The reaction undergoes without indole N-H-protection.     

Electroreductive intramolecular coupling of N-(oxoalkyl)phthalimides: complementary method to samarium(II) iodide reduction

The electroreductive intramolecular coupling of phthalimides with ketones in the presence of chlorotrimethylsilane gave five- and six-membered trans-cyclized products stereospecifically (>99%). Similar electroreductive intramolecular coupling of phthalimides with aldehydes afforded five-, six-, and seven-membered trans-cyclized products stereoselectively (75-93%). On the other hand, the reductive coupling of N-(oxoalkyl)phthalimides with samarium(II) iodide gave cis-cyclized products stereoselectively (88->99%).     

Intramolecular double or triple Suzuki coupling reaction of substituted di- or tribromobenzenes. An easy synthesis of fused tri- or tetracycles with a benzene core

Double or triple intramolecular Suzuki coupling reaction has been developed for the efficient synthesis of tri- or tetracyclic products with a benzene core in good yields. The reaction was realized via a one-pot procedure combining the hydroboration of the CC bond in the starting aryl halides and the intramolecular Suzuki coupling.     

Microwave-assisted synthesis of macrocycles via intramolecular and/or bimolecular Ullmann coupling

Microwave-assisted synthesis of macrocyclic diaryl ethers via intramolecular and/or bimolecular Ullmann coupling is described. Using the optimized conditions, a panel of macrocycles, with different substitution patterns, ring sizes, and linkers, has been successfully synthesized using microwave irradiation. To the best of our knowledge, this work represents the first examples of the microwave-assisted synthesis of macrocyclic diaryl ethers via intramolecular and/or bimolecular Ullmann coupling.     

Covalent Template-Directed Synthesis of a Spoked 18-Porphyrin Nanoring**

Rings of porphyrins mimic natural light-harvesting chlorophyll arrays and offer insights into electronic delocalization, providing a motivation for creating larger nanorings with closely spaced porphyrin units. Here, we demonstrate the first synthesis of a macrocycle consisting entirely of 5,15-linked porphyrins. This porphyrin octadecamer was constructed using a covalent six-armed template, made by cobalt-catalyzed cyclotrimerization of an H-shaped tolan with porphyrin trimer ends. The porphyrins around the circumference of the nanoring were linked together by intramolecular oxidative meso-meso coupling and partial β-β fusion, to give a nanoring consisting of six edge-fused zinc(II) porphyrin dimer units and six un-fused nickel(II) porphyrins. STM imaging on a gold surface confirms the size and shape of the spoked 18-porphyrin nanoring (calculated diameter: 4.7 nm).     

Synthesis of indolequinones via a Sonogashira coupling/cyclization cascade reaction

A mild strategy for constructing indolequinone motifs is described on the basis of the Sonogashira reaction and a copper-catalyzed intramolecular cyclization cascade reaction. The first step involves the palladium- and copper-catalyzed reaction between halogenated naphthoquinone and terminal acetylene to generate a coupling product, which then reacts in a copper-catalyzed intramolecular cyclization with the nitrogen functional group adjacent to the carbon-carbon triple bond.     

Assessing weak intramolecular donor-acceptor interactions using 1H-117Sn J-HMQC spectroscopy

It is demonstrated that long-range nJ(1H,117Sn) coupling constants down to 0.3 Hz, can be accurately quantified from non-linear fitting of the sine modulation of the associated 1H-117Sn correlation cross-peak intensities sampled as a function of the heteronuclear antiphase coherence preparation time in the 1H-117Sn J-HMQC pulse sequence. The contribution of additional, undesired modulations is illustrated and assessed using the product operator formalism, and is traced back to contributions that arise from miss-setting of the wandering 180 degrees pulse angle in the constant time period. The power of the method and its use in the characterization of weak intramolecular donor-acceptor interactions are illustrated by the determination of long-range nJ(1H,117Sn) coupling constants of bis[3-(dimethylamino)propyl]tin derivatives, [Me2N(CH2)3]2SnR2 (', R = Me; 3, R = Ph; 4, R = t-Bu). By comparing these with the values found for the corresponding bis(4-methylpentyl)tin derivatives, [Me2CH(CH2)3]2SnR2 (2', R = Me; 3', R = Ph), which lack such interactions, the use of long-range coupling constants to detect intramolecular donor-acceptor interactions is evaluated. It is concluded that nJ(1H,117Sn) couplings up to six bonds through an organic carbon chain can be quantified, whether donor-acceptor interactions are present or not. Furthermore, evidence is presented that, when two scalar coupling pathways co-exist, the pathway involving an intramolecular donor-acceptor interaction can have opposite sign, thus decreasing the overall coupling constant to a value smaller than that actually measured in the absence of a donor-acceptor interaction, where only one coupling pathway is active. There is nevertheless clear numerical value discrimination in the series of compounds investigated between long-range couplings in derivatives without weak intramolecular donor-acceptor interactions and those where such interactions can exist.     

铜试剂在有机合成中的应用研究进展

铜试剂催化的偶联反应是直接构建碳 碳键最有效的方法之一。本文综述了铜试剂催化的偶联反应构筑六种碳 碳键的方法;重点阐述了铜试剂催化构筑C(SP²)-C(SP²)的研究进展,含分子间偶联和分子内偶联。参考文献44篇。     

Total syntheses of amphidinolides T1 and T4 via catalytic, stereoselective, reductive macrocyclizations

Described in this work are total syntheses of amphidinolides T1 and T4 using two nickel-catalyzed reductive coupling reactions of alkynes, with an epoxide in one case (intermolecular) and with an aldehyde in another (intramolecular). The latter was used to effect a macrocyclization, form a C-C bond, and install a stereogenic center with >10:1 selectivity in both natural product syntheses. Alternative approaches in which intermolecular alkyne-aldehyde reductive coupling reactions would serve to join key fragments were investigated and are also discussed; it was found that macrocyclization (i.e. intramolecular alkyne-aldehyde coupling) was superior in several respects (diastereoselectivity, yield, and length of syntheses). Alkyne-epoxide reductive couplings were instrumental in the construction of key fragments corresponding to approximately half of the molecule of both natural products. In one case (T4 series), the alkyne-epoxide coupling exhibited very high site selectivity in a coupling of a diyne. A model for the stereoselectivity observed in the macrocyclizations is also proposed.