Gold(I)-catalyzed ring expansion of cyclopropanols and cyclobutanols

The rearrangement of 1-alkynyl cyclobutanols and cyclopropanols to alkylidene cycloalkanones catalyzed by cationic triarylphosphine gold(I) complexes is described. The reaction tolerates terminal alkynes as well as alkyl, aryl, and halo-substitution at the acetylenic position and stereoselectively provides a single olefin isomer. The gold(I)-catalyzed rearrangement is stereospecific with regard to substituents on the ring, thus providing a practical method for the stereoselective synthesis of highly substituted cyclopentanones from cyclopropanols. The reaction stereoselectively provides a single olefin isomer and is stereospecific with regard to substituents on the ring via sequential gold(I)-catalyzed ring expansion reactions.     

BiCl3-catalyzed propargylic substitution reaction of propargylic alcohols with C-, O-, S- and N-centered nucleophiles

A general and efficient BiCl3-catalyzed substitution reaction of propargylic alcohols with carbon and heteroatom-centered nucleophiles such as allyl trimethylsilane, alcohols, aromatic compounds, thiols and amides, leading to the construction of C-C, C-O, C-S and C-N bonds, has been developed.     

Domino reactions that combine an azido-Schmidt ring expansion with the Diels-Alder reaction

[reaction: see text] The combination of the intramolecular Schmidt reaction with the Diels-Alder reaction provides expedient access to a variety of heterocycles. Two different modes of reaction planning are presented. In one, the azide and ketone moieties necessary for the intramolecular Schmidt reaction originate on different molecules that are reacted and subsequently undergo a ring-adjustment step. Alternatively, an azido ketone can be used provided the ketone is deactivated by its presence in an enone.     

Palladium-catalyzed enantiospecific reaction of propargylic carbonates with phenols: cascade chirality transfer

[reaction: see text] A cascade chirality transfer process has been achieved by the palladium-catalyzed reaction of substituted propargylic carbonates with phenols. The reaction proceeds in a highly enantiospecific manner to produce chiral cyclic carbonates, which supports the existence of the pi-propargylpalladium intermediate in the reaction mechanism. The (E)- and (Z)-selectivity of the products can be controlled by choice of the phosphine ligand.     

Reactions of novel trifluoromethyl propargylic carbocation with carbon nucleophiles

Trifluoromethyl propargylic carbocation [I] generated from the reaction of 1-amino substituted 3-trifluoromethyl-2-propynyl trimethylsilyl ether 1 with TMSOTf in CH₂Cl₂ at −15 °C, followed by warming to room temperature reacted with 1.2 equiv of substituted benzenes, RMgBr and allylsilane to give the enones 3a-l and 5, respectively. The reaction of [I] with anisole, followed by treatment with Grignard reagents afforded the corresponding allyl amine derivatives 7, which underwent cyclization reaction to give indene derivatives 8 by using 2 equiv of TMSOTf.     

Type 3 ring opening reaction of cyclopropanated oxabenzonorbornadienes with alcohol nucleophiles

The first examples of a Type 3 ring opening reaction of cyclopropanated oxabenzonorbornadiene (CPOBD) were found to occur using alcohol nucleophiles under acid catalyzed conditions, yielding seven-membered rings via ring expansion. Optimization of the reaction determined the ideal conditions to be 10?mol% pTsOH at 40?°C using excess alcohol nucleophile as the solvent. The scope of the reaction investigated diverse alcohol nucleophiles and bridgehead substituents on the CPOBD; in both cases the steric properties of the substituent was found in influence the yield of the reaction. Alternative Type 3 products were observed when the bridgehead substituent was an ethyl or hydroxymethyl group and limited examples of Type 3 products were formed using a palladium catalyst with alcohol nucleophiles. Mechanisms have been proposed for the formation of the Type 3 product as well as the alternative Type 3 products.     

Highly regioselective synthesis of 2,3-disubstituted indenes via a novel palladium-catalyzed cyclization reaction of propargylic carbonates with carbon nucleophiles

Palladium-catalyzed reaction of propargylic carbonates with carbon nucleophiles offers an efficient, direct route to highly substituted indenes. The reaction conditions and the scope of the process are examined, and a possible mechanism is proposed. [reaction: see text]     

Ruthenium-catalyzed propargylic substitution reactions of propargylic alcohols with oxygen-, nitrogen-, and phosphorus-centered nucleophiles

The scope and limitations of the ruthenium-catalyzed propargylic substitution reaction of propargylic alcohols with heteroatom-centered nucleophiles are presented. Oxygen-, nitrogen-, and phosphorus-centered nucleophiles such as alcohols, amines, amides, and phosphine oxide are available for this catalytic reaction. Only the thiolate-bridged diruthenium complexes can work as catalysts for this reaction. Results of some stoichiometric and catalytic reactions indicate that the catalytic propargylic substitution reaction proceeds via an allenylidene complex formed in situ, whereby the attack of nucleophiles to the allenylidene C(gamma) atom is a key step. Investigation of the relative rate constants for the reaction of propargylic alcohols with several para-substituted anilines reveals that the attack of anilines on the allenylidene C(gamma) atom is not involved in the rate-determining step and rather the acidity of conjugated anilines of an alkynyl complex, which is formed after the attack of aniline on the C(gamma) atom, is considered to be the most important factor to determine the rate of this catalytic reaction. The key point to promote this catalytic reaction by using the thiolate-bridged diruthenium complexes is considered to be the ease of the ligand exchange step between a vinylidene ligand on the diruthenium complexes and another propargylic alcohol in the catalytic cycle. The reason why only the thiolate-bridged diruthenium complexes promote the ligand exchange step more easily with respect to other monoruthenium complexes in this catalytic reaction should be that one Ru moiety, which is not involved in the allenylidene formation, works as an electron pool or a mobile ligand to another Ru site. The catalytic procedure presented here provides a versatile, direct, and one-step method for propargylic substitution of propargylic alcohols in contrast to the so far well-known stoichiometric and stepwise Nicholas reaction.     

Some reactions of Ni-Mo and Ni-W propargylic cations with nucleophiles

Preliminary reactions of the metal stabilized carbocationic species [(η-C₅H₅)Ni(μ-η²(Ni),η³(Mo)-HC₂CMe₂)Mo(CO)₂(η-C₅H₄Me)]⁺ BF₄⁻ (Ni-Mo) with nucleophiles are reported. The Ni-Mo cationic propargylic complex undergoes nucleophilic attack by sodium methoxide to regenerate the neutral μ-alkyne complex [(η-C₅H₅)Ni{μ-η²,η²-HC₂CMe₂(OMe)}Mo(CO)₂(η-C₅H₄Me)] (Ni-Mo), from which the stabilized carbocation was originally derived by protonation. The new complexes [(η-C₅H₅)Ni{μ-η²,η²-HC₂CMe₂(C₅H₅)}Mo(CO)₂(η-C₅H₄Me)] (Ni-Mo), which exist as an inseparable mixture of 1(c)-1,3- and 2(c)-1,3-cyclopentadienyl isomers, were also obtained. When the Ni-Mo cations were treated with potassium t-butoxide, the alkyne isomers with pendant 1(c)-1,3- and 2(c)-1,3-cyclopentadienyl groups are also formed. The μ-hydroxyalkyne complex [(η-C₅H₅)Ni{μ-η²,η²-HC₂CMe₂(OH)}-Mo(CO)(η-C₅H₄Me)] (Ni-Mo) was also isolated concurrently, and presumably arises from nucleophilic attack of fortuitously present hydroxide ions in the BuO⁻ reagent on the Ni-Mo cation. When NaBH₄ was added to the Ni-Mo propargylic, nucleophilic attack by hydride resulted and the μ-ⁱPrC₂H heterobimetallic complex [(η-C₅H₅)Ni{μ-η²,η²-HC₂Prⁱ}Mo(CO)₂(η-C₅H₄Me)] (Ni-Mo) was recovered in good yield. Small quantities of other side-products were isolated and characterized spectroscopically. Some tantalizing differences in reactivity were observed when the corresponding Ni-W stabilized carbocation was reacted with methoxide ions. When the not fully characterized solid formed by protonating [(η-C₅H₅)Ni(μ-η²,η²-{HC₂CMe₂)(OMe)}W(CO)₂(η-C₅H₄Me)] (Ni-W) was treated with methoxide ions, regioisomers (1(c)-1,3- and 2(c)-1,3-cyclopentadienyl species) of composition [(η-C₅H₅)Ni{μ-η²,η²-HC₂CMe₂(C₅H₅)}W(CO)₂(η-C₅H₄Me)] (Ni-W) were formed. Direct reaction of the pure cation [(η-C₅H₅Niμ-η²,η³-HC₂CMe₂)W(CO)₂(η-C₅H₄Me)]⁺ (Ni-W) with methoxide also generated the same 1(c)-1,3- and 2(c)-1,3-cyclopentadiene-substituted alkyne complexes. Unlike the case with the Ni-Mo complexes, the initial μ-HC₂CMe₂(OMe) species was not regenerated.     

Palladium-catalysed biscyclisation of allenic bromoalkenes through a zipper-mode cascade

Treatment of allenic bromoalkenes bearing a nucleophilic moiety with a catalytic amount of palladium(0) in the presence of TBAF or Cs(2)CO(3) in MeCN affords bicyclic heterocycles in good to high yields, through zipper-mode cascade cyclisation.     

Novel platinum-catalysed cascade reactions: cyclisation, ring expansion and 1,2-oxygen shift reaction of a camphor-derived diyne

2,3-Bis(ethynyl)-3-hydroxy-camphorsultam was converted in one step into a novel tetracyclic cyclopentenone derivative, in an unprecedented platinum-catalysed cascade reaction. In the course of this reaction, cyclisation of the alkynes takes place, together with a ring expansion of the camphor skeleton and 1,2-migration of an oxygen atom. The structure of the unexpected product was analysed in detail by one- and two-dimensional NMR spectroscopy, and validated with the help of quantum mechanical calculations (B3LYP/6-31G^∗∗ and B3LYP/6-31+G(2df)) of the IR vibrational frequencies and the ¹H and ¹³C isotropic chemical shifts.     

Ruthenium-catalyzed propargylic substitution reaction of propargylic alcohols with thiols: a general synthetic route to propargylic sulfides

A novel cationic methanethiolate-bridged diruthenium complex [Cp*RuCl(mu2-SMe)2RuCp*(OH2)]OTf (1e) has been disclosed to promote the catalytic propargylic substitution reaction of propargylic alcohols bearing not only terminal alkyne group but also internal alkyne group with thiols. It is noteworthy that neutral thiolate-bridged diruthenium complexes (1a-1c), which were known to promote the propargylic substitution reactions of propargylic alcohols bearing a terminal alkyne group with various heteroatom- and carbon-centered nucleophiles, did not work at all. The catalytic reaction described here provides a general and environmentally friendly preparative method for propargylic sulfides, which are quite useful intermediates in organic synthesis, directly from the corresponding propargylic alcohols and thiols.     

Nickel-catalyzed reactions of silacyclobutanes with aldehydes: ring opening and ring expansion reaction

[reaction: see text]. The nickel-catalyzed ring opening reaction of silacyclobutanes with aldehydes affords the corresponding alkoxyallylsilanes. In contrast, the ring expansion reaction of benzosilacyclobutene with aldehydes occurs under nickel catalysis to give oxasilacyclohexenes.     

A ring expansion reaction of 1,3-oxathiolanes

1,3-Oxathiolanes are efficiently converted, via sulfur ylide intermediates, to 1,4-oxathianes by ring expansion with a silylated diazoacetate in the presence of a copper catalyst.     

Systems with annulated thioxo azepinone moiety: an access through heterocyclic carbodithioate ring expansion

New 1-oxo-2-thioxo-1,2,4,5-tetrahydrobenz[d]azepine and 1-oxo-2-thioxo-1,2,4,5-tetrahydroazepino[4,5-b]indole derivatives were conveniently obtained by the novel recyclization reaction of (methylthio)carbonothioylsubstituted heterocyclic quaternary salts with expansion of the dihydropyridine ring.     

Synthesis of 2-alkylidenecyclopentanones via palladium-catalyzed carbopalladation/ring expansion of 1-(1-alkynyl)cyclobutanols

The palladium-catalyzed cross-coupling of aryl halides or vinylic halides or triflates and 1-(1-alkynyl)cyclobutanols affords good yields of stereoisomerically pure 2-arylidene- or 2-(2-alkenylidene)cyclopentanones, respectively. The process involves (1) oxidative addition of the organic halide or triflate to Pd(0), (2) regioselective, intermolecular carbopalladation of the carbon-carbon triple bond of the 1-(1-alkynyl)cyclobutanol to produce a vinylic palladium intermediate, (3) regioselective ring expansion to a palladacycle, and (4) reductive elimination of the 2-alkylidenecyclopentanone with simultaneous regeneration of the Pd(0) catalyst. Generally, the best results are obtained by employing 10 mol % of Pd(OAc)(2), 20 mol % of PPh(3), 2 equiv of the aryl or vinylic iodide or vinylic triflate, 2 equiv of diisopropylethylamine, and n-Bu(4)NCl in DMF as the solvent.     

Computational study of the mechanism and selectivity of palladium-catalyzed propargylic substitution with phosphorus nucleophiles

The mechanism and sources of selectivity in the palladium-catalyzed propargylic substitution reaction that involves phosphorus nucleophiles, and which yields predominantly allenylphosphonates and related compounds, have been studied computationally by means of density functional theory. Full free-energy profiles are computed for both H-phosphonate and H-phosphonothioate substrates. The calculations show that the special behavior of H-phosphonates among other heteroatom nucleophiles is indeed reflected in higher energy barriers for the attack on the central carbon atom of the allenyl/propargyl ligand relative to the ligand-exchange pathway, which leads to the experimentally observed products. It is argued that, to explain the preference of allenyl- versus propargyl-phosphonate/phosphonothioate formation in reactions that involve H-phosphonates and H-phosphonothioates, analysis of the complete free-energy surfaces is necessary, because the product ratio is determined by different transition states in the respective branches of the catalytic cycle. In addition, these transition states change in going from a H-phosphonate to a H-phosphonothioate nucleophile.