Synthesis of the C6–C18 bis-tetrahydrofuran fragment of the proposed structure of iriomoteolide-2a via stepwise double SN2 cyclization reactions

The C6–C18 bis-tetrahydrofuran (bis-THF) fragment of the proposed structure of iriomoteolide-2a has been synthesized via stepwise double intramolecular S_N2-type etherifications. The C11 and C16 stereogenic centers could be secured in the forms of propargyl alcohols by asymmetric transfer hydrogenation of the corresponding propargyl ketones. The C9–C12 THF ring was first constructed via a tandem asymmetric dihydroxylation (AD)–S_N2 sequence while the C13–C16 THF ring was later installed via an intramolecular S_N2 reaction of a chiral propargyl mesylate. During the latter THF ring formation, epimerization at the propargylic carbon was not observed. Since the initially proposed (9R,11S,12R) configuration of iriomoteolide-2a has recently been revised to (9S,11R,12S), the established synthesis of the C6–C18 bis-THF fragment could be easily amended by using the opposite enantiomers of the chiral ligands for AD and asymmetric transfer hydrogenation.     

The synthetic potential of α,α-diallylcyrene

The reaction of cyrene with allyl bromide in THF in the presence of Bu^tOK gave the α,α-diallyl derivative of cyrene in 50% yield. This derivative smoothly undergoes iodo- cyclization on the keto group that is converted into a ketal center to give annulated bis-tetrahydrofuran; intramolecular cationic cyclization in the presence of SnCl₄ or TiCl₄ results in 2-oxabicyclo[3.3.1]nonan-9-ones. The prospects of using these reactions towards the synthesis of trichothecene sesquiterpenoids modified in the central moiety were assessed.     

Communiols A-D: new mono- and bis-tetrahydrofuran derivatives from the coprophilous fungus Podospora communis

Communiols A-D (1-4), new tetrahydrofuran and bis-tetrahydrofuran derivatives, have been isolated from cultures of the coprophilous fungus Podospora communis, and identified by spectroscopic methods.     

Stereoselective synthesis of bis-hydroxy-tetrahydrofurans using cross metathesis

A short asymmetric approach for the synthesis of bis-tetrahydrofuran units of various annonaceous acetogenins is described. The key steps of the synthesis are self-cross metathesis and Sharpless asymmetric dihydroxylation.     

Synthesis of (+)-bullatacin via the highly diastereoselective [3+2] annulation reaction of a racemic aldehyde and a nonracemic allylsilane

[reaction: see text] A total synthesis of (+)-bullatacin has been accomplished via a diastereoselective [3+2] annulation reaction of the highly enantiomerically enriched allylsilane 3 and racemic aldehyde 4, which provides the key bis-tetrahydrofuran fragment 15 with > or = 20:1 ds.     

Stereodivergent approach to both syn- and anti-isomers of γ-amino-β-hydroxy acids: (3S,4S)- and (3R,4S)-AHPPA derivatives

A stereodivergent approach employing an N-hydroxymethyl group has been utilized to produce both diastereomeric derivatives of (3S,4S)-AHPPA 3 and (3R,4S)-AHPPA 4, via an intramolecular conjugate addition and an intramolecular epoxidation, respectively. The selectivity of the intramolecular conjugate addition was more than 10:1 while that of the intramolecular epoxidation was more than 1:20.     

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.     

Synthesis of 4,5-fused tricyclic quinolines via an acid-promoted intramolecular Friedel–Crafts allenylation of aniline derivatives

A novel method for synthesizing 4,5-fused tricyclic quinoline derivatives based on an acid-promoted intramolecular Friedel–Crafts allenylation of anilines. Using aryl group-substituted propargyl alcohol derivatives with a meta-substituted N-Boc aniline unit as substrates, a four-step reaction sequence involving an acid-promoted intramolecular Friedel–Crafts allenylation of anilines, an acid-promoted intramolecular C–N bond formation, deprotection of the Boc group, and air oxidation proceeded in a single pot, producing the corresponding 4,5-fused tricyclic quinoline derivatives in 31–84% yield.     

Regioselective synthesis of C-prenylated flavonoids via intramolecular [1,3] or [1,5] shift reaction catalyzed by acidic clays

Prenyl side chain and dihydropyrano skeleton exists in many natural and synthetic biologically active flavonoids. A highly efficient and regioselective method for the synthesis of C-prenylated flavonoids via intramolecular [1,3] or [1,5] shift reaction of 5-O-prenylflavonoids catalyzed by Florisil or Montmorillonite clays is described. Florisil catalyzes intramolecular [1,5] shift reaction of 5-O-prenylflavonoids to obtain 8-C-prenylated flavonoids exclusively, Montmorillonite K10 exhibits the superior selectivity to promote intramolecular [1,3] shift reaction to obtain 6-C-prenylated flavonoids compared with Florisil and Montmorillonite KSF. This method provides a practical process to regioselective synthesize biologically important C-prenylated flavonoids in good yields using commercially available and inexpensive catalyst under mild conditions.     

3 + 2]-annulation reactions of chiral allylsilanes and chiral aldehydes. studies on the synthesis of bis-tetrahydrofuran substructures of annonaceous acetogenins

[Structure: See text] Double asymmetric [3 + 2]-annulation reactions of chiral beta-silyloxyallylsilanes with chiral 2-tetrahydrofuranyl carboxaldehydes have been studied, leading to the stereocontrolled synthesis of six diastereomeric bis-tetrahydrofuran structures corresponding to the core subunits of members of the Annonaceous acetogenin family of natural products. Transition-state models are proposed to account for the stereoselectivity of the double-stereodifferentiating [3 + 2]-annulation reactions.     

Naryl-substituted anthranilamides with intramolecular hydrogen bonds

Hydrogen bonding interaction as one type of non-covalent force has proven itself to be highly efficient for constructing structurally unique artificial secondary structures. Here, the structure of N_aryl-substituted anthranilamide in solution is demonstrated by various NMR technique, the intramolecular hydrogen bonds between amide attached to arylamine of the same ring is proposed, which is supported by its crystal structure in the solid phase. The substituent on the nitrogen atom of arylamine plays an important role in forming the presence of intramolecular hydrogen bonds. The chemical shift of the N_aryl-H downfield changes obviously, due to the formation of intramolecular hydrogen bonds and the deshielding effect of oxygen, and the neighboring C–H is activated and shows downfield protonic signal too. The presence of intramolecular hydrogen bonds probably provides the explanation for the transformation from N_aryl-substituted anthranilamide to imine, which could be converted into 2-aryl quinazolinone finally.     

A novel carbanion-olefin intramolecular cyclization: synthesis of substituted 2-aroyl-3,4-dihydro-2H-benzopyrans from salicylaldehydes

Utilization of a novel carbanion-olefin intramolecular 6-endo-trig cyclization reaction to provide 2-aroyl-3,4-dihydro-2H-benzopyrans is described. Through a sequence of a Wittig reaction, O-alkylation, and carbanion-olefin intramolecular cyclization, salicylaldehydes were converted into a series of new 2-aroyl-3,4-dihydro-2H-benzopyrans in two steps or in one-pot reaction.     

Infrared study of intramolecular coordination in (chloromethyl)- and (dichloromethyl)-germanes

Frequencies (ν) and integrated intensities (A) of GeH stretching modes in the IR spectra of (diorgano)germanes containing GeCH₂Cl and GeCHCl₂ fragments have been measured. Anomalous values of ν and A (compared to those expected from the inductive effect only) are explained by intramolecular coordination between chlorine and germanium atoms. The enthalpy of intramolecular coordination (ΔH) has been determined by IR spectroscopy. The enthalpy of intramolecular coordination is shown to increase with the acceptor properties of the substituents bonded to the germanium atom in (dorgano)- and (triorgano)-germanes.     

Total synthesis of asimicin via highly stereoselective [3 + 2] annulation reactions of substituted allylsilanes

A highly stereoselective total synthesis of (+)-asimicin (1) is reported. The synthesis features two chelate-controlled [3 + 2] annulation reactions-one of which (e.g., 2 + 3) constitutes a key, convergent fragment assembly step-that establish all of the stereochemistry of the bis-tetrahydrofuran unit of the natural product.     

Intramolecular excimer formation in macromolecules—V. Head-to-head polystyrene,block copolymers of styrene and butadiene and regular condensation polymers of α-methylstyrene

Studies of the photophysical properties of head-to-head polystyrene, block copolymers poly(butadiene-b-styrene) and polystyrenes of various sequence length of styrene chromophore and regular copolymers of α-methylstyrene indicate that interactions between phenyl chromophores located distantly upon the macromolecule are not of major significance in determination of excimer formation in styrene polymers. It is concluded that intramolecular excimer formation in polystyrenes occurs primarily as a consequence of interactions between nearest neighbour chromophores in the polymer chain. The influence of polymer coil dimensions upon intramolecular excimer formation is demonstrated. The photophysical behaviour of poly(butadiene-b-styrene) block copolymers shows the importance of intramolecular energy migration in population of potential excimer sites.     

Polycyclic N-heterocyclic compounds. Part 61: A novel Truce-Smiles type rearrangement reaction of 4-(2-cyanovinyloxy)butanenitriles to give cycloalkeno[1,2-d]furo[2,3-b]pyridines

The cycloalkeno[1,2-d]furo[2,3-b]pyridine skeleton was conveniently synthesized from fused 4-(2-cyanovinyloxy)butanenitriles in one step through sequential intramolecular Michael addition, β-elimination and intramolecular nucleophilic addition. This sequence thus consists of a novel Truce-Smiles type rearrangement followed by cyclization. The 5-amino derivatives were transformed further to lactams in good yields.     

Propargyl mediated intramolecular aglycon delivery (IAD): applications to the synthesis of core N-glycan oligosaccharides

The use of propargyl mediated intramolecular aglycon delivery (IAD) for the synthesis of the key Manβ(1→4)GlcNAc linkage of N-glycan oligosaccharides, including the core N-glycan pentasaccharide, is investigated. Isomerisation of a 2-O-progargyl group of manno thioglycoside donors to an allene is followed by iodonium ion mediated mixed acetal formation with the 4-OH of protected GlcNAc acceptors, and subsequent intramolecular glycosylation occurs with complete control of anomeric stereochemistry to form the Manβ(1→4)GlcNAc linkage. A variety of linear and convergent approaches (1+2, 3+1, 3+2) to the core pentasaccharide are investigated as means of probing the generality and limitations of this type of intramolecular aglycon delivery for the formation of β-mannoside linkages in complex oligosaccharides.     

A novel intramolecular Ugi 3CC for the synthesis of N-alkyl-3-oxo-2-aryl-1,2,3,4-tetrahydropyrazino[1,2-a]indole-1-carboxamides

An intramolecular Ugi reaction of 2-(2-formyl-1H-indol-1-yl)acetic acid with aryl amines and isocyanides has been developed to produce a novel class of N-alkyl-3-oxo-2-aryl-1,2,3,4-tetrahydropyrazino[1,2-a]indole-1-carboxamides in good yields. This is the first report on intramolecular Ugi three component reaction of 2-(2-formyl-1H-indol-1-yl)acetic acid, aryl amine, and isonitrile.     

The consecutive [2+2] cycloaddition-ring expansion route to diastereomeric 1,4-diazepin-5-ones from imino-ketenimines. Alternative intramolecular transamidation of β-lactams

Azeto[1,2-a]imidazoles are prepared by a formal intramolecular [2+2] cycloaddition of imino-ketenimines in which an ethylene chain is linking the nitrogen atoms of both functionalities, bearing a methyl and a phenyl group on the terminal carbon atom of the heterocumulene. By acid-catalyzed hydrolysis these azeto[1,2-a]imidazoles are converted into 6,6,7-trisubstituted hexahydro-1,4-diazepin-5-ones, which have been alternatively prepared via intramolecular transamidation of N-(2-aminoethyl)-β-lactams.