Selective O‐allylation of bisphenol A: toward a chloride‐free route for epoxy resins

The O‐allylation of bisphenol A (BPA) has been performed with the most selective catalysts for O‐allylation of phenols reported previously. Both the cyclopentadienyl–ruthenium catalysts and the palladium–diphosphine catalysts are capable of selectively performing single and double O‐allylation of BPA. An intriguing solvent effect is observed; the choice of the solvent is of key importance for both conversion and selectivity. The use of an excess of diallyl ether as allylating agent results in relatively high yields of the bisallyl ether of bisphenol A, while maintaining the high selectivity for O‐allylation. Copyright © 2010 John Wiley & Sons, Ltd.     

Diastereoselective ruthenium-catalysed cycloisomerisation of diallyllactones: preparation of exo-methylene spirolactones

Diallyllactones (obtained from cyclic anhydrides via a double allylation reaction promoted by titanium tetrachloride) were cycloisomerised using 5 mol% of cyclooctadienyl ruthenium dichloride in ethanol providing the corresponding exomethylene spirolactones in good yields, with moderated to good diastereomeric excess.     

Pentamethylcyclopentadienyl-ruthenium catalysts for regio- and enantioselective allylation of nucleophiles

Ruthenium(II) complexes containing the pentamethylcyclopentadienyl ligand efficiently perform the activation of allylic carbonates and halides to generate cationic and dicationic ruthenium(IV) complexes. This activation has been transferred as a key step to the catalytic allylation of nucleophiles. The structural and electronic properties of the allylic moieties lead to the regioselective formation of chiral products resulting from nucleophilic addition to their most substituted terminus. The catalytic activity of various Ru(Cp*) precatalysts in several allylic substitutions by C and O nucleophiles will be presented. The enantioselective version that has been demonstrated by using optically pure bisoxazoline ligands will also be discussed.     

Non-metathesis reactions of ruthenium carbene catalysts and their application to the synthesis of nitrogen-containing heterocycles

Non-metathesis reactions of ruthenium carbene catalysts, such as olefin isomerization, hydrogenation, radical reaction, activation of silane, cyclopropanation, epimerization cocyclopropane, [3 + 2] cycloaddition, and cycloisomerization, are summarized. The utility of these reactions was demonstrated by the synthesis of indole using olefin isomerization and subsequent ring-closing metathesis, the synthesis of indoline using cycloisomerization, and the synthesis of the putative structure of fistulosin using cycloisomerization as a key step.     

Enzyme‐ and Ruthenium‐Catalyzed Enantioselective Transformation of α‐Allenic Alcohols into 2,3‐Dihydrofurans

An efficient one‐pot method for the enzyme‐ and ruthenium‐catalyzed enantioselective transformation of α‐allenic alcohols into 2,3‐dihydrofurans has been developed. The method involves an enzymatic kinetic resolution and a subsequent ruthenium‐catalyzed cycloisomerization, which provides 2,3‐dihydrofurans with excellent enantioselectivity (up to >99 % ee). A ruthenium carbene species was proposed as a key intermediate in the cycloisomerization.     

Allylic Acetals as Acrolein Oxonium Precursors in Tandem C−H Allylation and [3+2] Dipolar Cycloaddition

The ruthenium(II)‐catalyzed C?H functionalization of (hetero)aryl azomethine imines with allylic acetals is described. The initial formation of allylidene(methyl)oxoniums from allylic acetals could trigger C(sp²)?H allylation, and subsequent endo‐type [3+2] dipolar cycloaddition of polar azomethine fragments to deliver valuable indenopyrazolopyrazolones. The utility of this method is showcased by the late‐stage functionalization of bioactive molecules such as estrone and celecoxib. Combined experimental and computational investigations elucidate a plausible mechanism of this new tandem reaction. Notably, the reductive transformation of synthesized compounds into biologically relevant diazocine frameworks highlights the importance of the developed methodology.     

Palladium-catalyzed allylation of α-isocyanocarboxylates

α-Isocyanocarboxylates underwent palladium-catalyzed allylation with allylic acetates, in which π-allylpalladium(II) intermediate was involved. The catalytic allylation of methyl α-isocyano(phenyl)acetate using an optically active ferrocenylphosphine ligand caused an asymmetric induction of up to 39% ee.     

Ruthenium-catalyzed oxidative C-H alkenylations of anilides and benzamides in water

A cationic ruthenium(II) complex enabled efficient oxidative alkenylations of anilides in water as a green solvent and proved applicable to double C-H bond functionalizations of (hetero)aromatic amides with ample scope. Detailed studies provided strong support for a change of ruthenation mechanism in the two transformations, with an irreversible metalation as the key step in cross-dehydrogenative alkenylations of benzamides.     

Palladium(II)-catalyzed cycloisomerization of substituted 1,5-hexadienes: a combined experimental and computational study on an open and an interrupted hydropalladation/carbopalladation/β-hydride elimination (HCHe) catalytic cycle

The Pd(II)-catalyzed cycloisomerization of 3-alkoxycarbonyl-3-hydroxy-substituted 1,5-hexadienes has been studied experimentally and computationally. Experimentally, the reaction is characterized by a rapid room temperature formation of monomeric as well as dimeric cycloisomerization products using the commercially available precatalyst [(CH(3)CN)(4)Pd](BF(4))(2). In situ NMR measurements indicate the initial kinetic advantage of the desired cycloisomerization pathway to methylene cyclopentanes; however, double bond isomerization, elimination, and dimer formation are competitive undesired pathways. Evaluation of the obtained product structures by NMR spectroscopy and X-ray crystallography indicates that the sole determinant for the monomer/dimer ratio is the regioselectivity of the initial hydropalladation in favor of the allylic (monomer formation) or the homoallylic double bond (dimer formation). In order to account for the experimental results, we propose the coexistence of two product-forming catalytic cycles, an open, monomer generating, as well as an interrupted and redirected, dimer generating, hydropalladation/carbopalladation/β-hydride elimination (HCHe) process. Results from computational studies of the proposed competing catalytic cycles are supportive to our mechanistic hypothesis and pinpoint the pivotal importance of Pd(II)-hydroxo-chelate complexes for the reactivity-stability interplay of on- and off-pathway intermediates.     

A concise synthetic route to the conduritols from pentoses

A short synthetic strategy for preparation of the conduritols is described. The key step employs a zinc-mediated fragmentation of protected methyl 5-deoxy-5-iodo-d-pentofuranosides followed by an allylation of the intermediate aldehyde in the same pot. The allylation is performed with 3-bromopropenyl benzoate and occurs with good diastereoselectivity. An amino group can be introduced in the product by trapping the intermediate aldehyde as the imine prior to the allylation. The functionalised 1,7-octadienes, thus obtained, are converted into protected conduritols by ring-closing olefin metathesis.     

Preparation of a Key Intermediate for the Synthesis of the (±)-Pentalenolactone E Methyl Ester by Catalytic ‘Palladium-Ene Cyclization’/Methoxycarbonylation

Bicyclic alcohol (±)- 2 , an advanced intermediate for the synthesis of the methyl ester 1 of pentalenolactone E, has been synthesized in nine operations starting from aldehyde 7 . The key step 6 → 9 is a Pd-catalyzed, tandem intramolecular alkyne allylation/carbonylation reaction.     

First enantioselective total synthesis of (+)-(R)-Pinnatolide using an asymmetric domino allylation reaction

An efficient total synthesis of (+)-(R)-Pinnatolide is described. As a key step an asymmetric multicomponent domino allylation reaction of methyl levulinate is used to form the quaternary stereogenic center in a highly selective way.     

Ruthenium‐Catalyzed Cycloisomerization of 2,2′‐Diethynyl‐ biphenyls Involving Cleavage of a Carbon–Carbon Triple Bond

A ruthenium complex catalyzes a new cycloisomerization reaction of 2,2′‐diethynylbiphenyls to form 9‐ethynylphenanthrenes, thereby cleaving the carbon–carbon triple bond of the original ethynyl group. A metal–vinylidene complex is generated from one of the two ethynyl groups, and its carbon–carbon double bond undergoes a [2+2] cycloaddition with the other ethynyl group to form a cyclobutene. The phenanthrene skeleton is constructed by the subsequent electrocyclic ring opening of the cyclobutene moiety.     

Development of isomerization and cycloisomerization with use of a ruthenium hydride with N-heterocyclic carbene and its application to the synthesis of heterocycles

A pure ruthenium hydride complex with N-heterocyclic carbene (NHC) ligand was efficiently generated from the reaction of a second-generation Grubbs ruthenium catalyst with vinyloxytrimethylsilane and unambiguously characterized. This ruthenium hydride complex showed high catalytic activity for the selective isomerization of terminal olefin and for the cycloisomerization of 1,6-dienes. These reactions of N-allyl-o-vinylaniline lead to novel synthetic methods for heterocycles such as indoles and 3-methylene-2,3-dihydroindoles, which are useful synthons for bioactive natural products. These procedures address an important issue in diversity-oriented synthesis.     

Double cycloisomerization as a novel and expeditious route to tricyclic heteroaromatic compounds: short and highly diastereoselective synthesis of (+/-)-tetraponerine T6

[reaction: see text] Cu-Assisted double cycloisomerization of bis-alkynylpyrimidines afforded the 5-6-5 tricyclic heteroaromatic skeleton. This transformation was used as a key step in the highly diastereoselective total synthesis of (+/-)-tetraponerine T6.     

A Combined Experimental and Computational Study on the Cycloisomerization of 2‐Ethynylbiaryls Catalyzed by Dicationic Arene Ruthenium Complexes

Ruthenium‐catalyzed cycloisomerization of 2‐ethynylbiaryls was investigated to identify an optimal ruthenium catalyst system. A combination of [η⁶‐(p‐cymene)RuCl₂(PR₃)] and two equivalents of AgPF₆ effectively converted 2‐ethynylbiphenyls into phenanthrenes in chlorobenzene at 120 °C over 20 h. Moreover, 2‐ethynylheterobiaryls were found to be favorable substrates for this ruthenium catalysis, thus achieving the cycloisomerization of previously unused heterocyclic substrates. Moreover, several control experiments and DFT calculations of model complexes were performed to propose a plausible reaction mechanism.     

Ring-closing olefin metathesis on ruthenium carbene complexes: model DFT study of stereochemistry

Ring-closing metathesis (RCM) is the key step in a recently reported synthesis of salicylihalamide and related model compounds. Experimentally, the stereochemistry of the resulting cycloolefin (cis/trans) depends strongly on the substituents that are present in the diene substrate. To gain insight into the factors that govern the observed stereochemistry, density functional theory (DFT) calculations have been carried out for a simplified dichloro(2-propylidene)(imidazole-2-ylidene)ruthenium catalyst I, as well as for the real catalyst II with two mesityl substituents on the imidazole ring. Four model substrates are considered, which are closely related to the systems studied experimentally, and in each case, two pathways A and B are possible since the RCM reaction can be initiated by coordination of either of the two diene double bonds to the metal center. The first metathesis yields a carbene intermediate, which can then undergo a second metathesis by ring closure, metallacycle formation, and metallacycle cleavage to give the final cycloolefin complex. According to the DFT calculations, the stereochemistry is always determined in the second metathesis reaction, but the rate-determining step may be different for different catalysts, substrates, and pathways. The ancillary N-heterocyclic carbene ligand lies in the Ru-Cl-Cl plane in the simplified catalyst I, but is perpendicular to it in the real catalyst II, and this affects the relative energies of the relevant intermediates and transition states. Likewise, the introduction of methyl substituents in the diene substrates influences these relative energies appreciably. Good agreement with the experimentally observed stereochemistry is only found when using the real catalyst II and the largest model substrates in the DFT calculations.     

Low temperature organocopper-mediated two-component cross coupling/cycloisomerization approach toward N-fused heterocycles

Organocopper reagents smoothly react with heterocyclic propargyl mesylates at low temperature to produce N-fused heterocycles. The copper reagent plays a "double duty" in this novel cascade transformation, which proceeds via an SN2' substitution followed by a subsequent cycloisomerization step.     

Synthesis of Substituted 1,3‐Diene Synthetic Equivalents by a Ru‐Catalyzed Diyne Hydrative Cyclization

Catalyzed by [CpRu(CH₃CN)₃]PF₆, the hydrative cyclization of dipropargylic sulfone substrates provides an effective way to synthesize highly functionalized substituted 3‐sulfolenes. The amount of water is crucial for the reactivity of this cycloisomerization reaction. The scope and limitations of the Ru‐catalyzed cycloisomerization are discussed. A marked ketone‐directing effect was observed for the first time in ruthenium‐catalyzed cyclizations. A plausible mechanism for the ketone‐directed cycloisomerization is also rationalized. The utility of this method was demonstrated by both sulfur dioxide extrusion of the 3‐sulfolenes to afford 1,3‐dienes and subsequent inter‐ or intramolecular Diels–Alder reactions.     

Gold-catalyzed synthesis of 1,3-disubstituted benzenes through tandem allylation/cyclization reaction of alkynals

Treatment of alkynals with 2-substituted allylsilanes and PPh₃AuCl/AgOTf (5/3 mol%) catalyst led to formation of 1,3-disubstituted benzenes efficiently. This reaction sequence comprises an initial allylation of aldehyde, followed by cycloisomerization of enynes; PPh₃AuOTf is active in both steps.