Silicon tetrachloride in organic synthesis: new applications for the vinylogous aldol reaction

This paper describes a novel and efficient methodology for vinylogous aldol reactions based on SiCl₄ catalysis. According to the nucleophilicity Mayr's scale, vinylogous aldol reaction of Chan's diene proved to be effective by using catalytic amount of SiCl₄, without any other promoter. On the contrary, the SiCl₄/Lewis base system has been conveniently exploited for the efficient and selective vinylogous reaction of less nucleophilic Danishefsky's diene and 2-trimethylsilyloxyfuran (TMSOF). Indeed, a number of Lewis bases, such as sulfoxides, formamides and phosphoramides have been successfully used as SiCl₄ promoters. TMSOF and silyloxydienes, resulting from 2,2,6-trimethyl-[1,3]-dioxin-4-one derivatives, required stoichiometric amount of SiCl₄, while vinylogous aldol reaction of Chan's and Danishefsky's dienes took satisfactorily place in the presence of catalytic or sub-stoichiometric amount of catalyst.     

Total synthesis of (+)-lepadin F

An enantioselective total synthesis of (+)-lepadin F is described. The synthetic sequence features an intermolecular aza-[3 + 3] annulation, homologation of a vinylogous amide via Eschenmoser's episulfide contraction, and a highly stereoselective hydrogenation essential for achieving the 1,3-anti relative stereochemistry at C2 and C8a.     

An entry to the azocino[4,3-b]indole framework through a dehydrogenative activation of 1,2,3,4-tetrahydrocarbazoles mediated by DDQ: formal synthesis of (±)-uleine

It is presented that hexahydro-1,5-methano[4,3-b]indoles were efficiently synthesized in high yields (up to 89% yield) through the cyclization reaction of starting tetrahydrocarbazoles bearing a monoalkylaminocarbonylmethyl moiety at the C-2 position mediated by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). A mechanistic proposal is also given that mainly includes two cascade reactions: (i) formation of a vinylogous iminium cation via DDQ-mediated dehydrogenation of tetrahydrocarbazole functionality and (ii) intra-molecular and syn-selective addition of the amide functionality as the nucleophile to the vinylogous iminium cation. Furthermore, this cyclization reaction was successfully utilized in the formal total synthesis of (±)-uleine, an Aspidospermatan skeletal type alkaloid.     

Organocatalytic Enantioselective Cross‐Vinylogous Rauhut–Currier Reaction of Methyl Coumalate with Enals

The organocatalytic enantioselective intermolecular cross‐vinylogous Rauhut–Currier (RC) reaction of methyl coumalate with α,β‐unsaturated aldehydes is reported, and the enals are activated by iminium catalysis to serve as the Michael acceptors and methyl coumalate is used as an activated diene to generate a latent enolate. The excellent selectivity is driven by the aromaticity of methyl coumalate, and the post transformation of this heterocyclic structure into other electron‐deficient arenes and heterocycles have addressed, in part, the challenging selectivity issues of the intermolecular cross‐RC reactions and the limited scope of iminium catalysis.     

Synthesis of functionalized piperidinones

A versatile, stereoselective synthesis of 5-hydroxypiperidinones with substituents at N1, C3, and C6 has been developed. The sequence involves ring-closing metathesis of a diene amide and epoxidation of the resulting alkene, followed by base-mediated elimination, and finally hydrogenation.     

Effect of the Nature of Coke-Forming Species on the Crystallographic Characteristics and Catalytic Properties of Metal–Filamentous Carbon Catalysts in the Selective Hydrogenation of 1,3-Butadiene

The particle morphology and surface structure of nickel metal in metal–filamentous carbon catalysts were found to depend on the nature of coke-forming species used in the synthesis of catalysts. Metal carbonization with hydrocarbons that are characterized by high thermodynamic stability results in the formation of well-cut metal particles the surface of which is formed by (110) facets. Selective hydrogenation reactions of diene and acetylene hydrocarbons to olefins are typical of these catalysts. In the catalytic decomposition of hydrocarbons with relatively low thermodynamic stability, metal particles become irregular in shape, and their surface is formed by (111) facets. In this case, the reactions of full hydrogenation of olefin, diene, and acetylene hydrocarbons to corresponding alkanes take place. These data are consistent with the found dependence of the catalytic properties of catalysts on the character of the exterior faceting of active metal particles.     

Organic solvent‐free catalytic hydrogenation of diene‐based polymer nanoparticles in latex form. Part II. Kinetic analysis and mechanistic study

The central challenge that has limited the development of catalytic hydrogenation of diene‐based polymer latex (i.e., latex hydrogenation) in large‐scale production pertains to how to accomplish the optimal interplay of accelerating the hydrogenation rate, decreasing the required quantity of catalyst, and eliminating the need for an organic solvent. Here, we attempt to overcome this dilemma through decreasing the dimensions of the polymer substrate (such as below 20 nm) used in the hydrogenation process. Very small diene‐based polymer nanoparticles were synthesized and then used as the substrates for the subsequent latex hydrogenation. The effects of particle size, temperature, and catalyst concentration on the hydrogenation rate were fully investigated. An apparent first‐order kinetic model was proposed to describe the rate of hydrogen uptake with respect to the concentration of the olefinic substrate (C?C). Mass transfer of both the hydrogen and catalyst involved in this solid (polymer)–liquid (water)–gas (hydrogen) three‐phase latex system is discussed. The competitive coordination of the catalyst between the C?C and acrylonitrile units within the copolymer was elucidated. It was found that (1) using very small diene‐based polymer nanoparticles as the substrate, the hydrogenation rate of polymer latex can be increased vastly to achieve a high conversion of 95% while a quite low level of catalyst loading is required; (2) this latex hydrogenation process was completely free of organic solvent and no cross‐linking was found; (3) the mass transfer of hydrogen is not a rate‐determining step in the present hydrogenation reactions; (4) the catalyst was dispersed homogeneously within the polymer nanoparticles; (5) for the reaction that has reached about 95 mol % conversion, the kinetic study shows that the reaction is chemically controlled with an apparent activation energy of 100–110 kJ/mol; (6) the strong coordination of C[tbond]N to the catalytically active species RhH₂Cl(PPh₃)₂ imposed a negative effect on the hydrogenation activity. The present research provides a comprehensive study to appreciate the underlying chemistry of latex hydrogenation of diene‐based polymer nanoparticles and more importantly shows great promise toward the commercialization of a “green” catalytic hydrogenation operation of a diene‐based polymer latex in industry. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Stereocontrolled IMDA reaction of styrene derivatives. A way to enantiopure 3a,4,9,9a-tetrahydrobenz[f]isoindolines

IMDA reactions on chiral perhydro-1,3-benzoxazines, derived from (-)-8-amino menthol, bearing a styrene substituent at C-2 acting as diene and an acryl amide acting as dienophile occur with high stereoselection and excellent chemical yields. After elimination of the chiral appendage, enantiopure 3a,4,9,9a-tetrahydrobenz[f]isoindolines are prepared in this way. The effect of the substituents at both diene and dienophile are studied, showing that a methyl group at C-1 in the diene inhibited the reaction, while the ene adduct, instead of the IMDA product, was obtained when a methyl group was at C-2.     

Lewis base activation of Lewis acids: catalytic, enantioselective vinylogous aldol addition reactions

The generality of Lewis base catalyzed, Lewis acid mediated, enantioselective vinylogous aldol addition reactions has been investigated. The combination of silicon tetrachloride and chiral phosphoramides is a competent catalyst for highly selective additions of a variety of alpha,beta-unsaturated ketone-, 1,3-diketone-, and alpha,beta-unsaturated amide-derived dienolates to aldehydes. These reactions provided high levels of gamma-site selectivity for a variety of substitution patterns on the dienyl unit. Both ketone- and morpholine amide-derived dienol ethers afforded high enantio- and diastereoselectivity in the addition to conjugated aldehydes. Although alpha,beta-unsaturated ketone-derived dienolate did not react with aliphatic aldehydes, alpha,beta-unsaturated amide-derived dienolates underwent addition at reasonable rates affording high yields of vinylogous aldol product. The enantioselectivities achieved with the morpholine derived-dienolate in the addition to aliphatic aldehydes was the highest afforded to date with the silicon tetrachloride-chiral phosphoramide system. Furthermore, the ability to cleanly convert the morpholine amide to a methyl ketone was demonstrated.     

Synthesis, characterization, and reactivity of ruthenium diene/diamine complexes including catalytic hydrogenation of ketones

Thermal reactions between [RuCl2(diene)]n (diene = 2,5-norbornadiene, nbd; 1,5-cyclooctadiene, cod) with an excess of N,N,N',N'-tetramethylethylene diamine (tmeda) afforded derivatives [RuCl2(diene)(tmeda)] (diene = nbd, 1; cod, 2) as a mixture of cis and trans isomers. When thermolysis was performed under H2 mixtures of hydride species [RuCl(H)(diene)(tmeda)] (diene = nbd, 3; cod, 4) and the bis-tmeda adduct trans-[RuCl2(tmeda)2] (5) were obtained in different ratios depending upon the reaction conditions and reaction times. Heating polymeric Ru(II) precursors in toluene in the presence of a 5-fold excess of the bulkier N,N,N',N'-tetraethylethylene diamine (teeda) resulted in a rare diamine dealkylation process with formation of trans-[RuCl2(nbd)(Et2NCH2CH2NHEt)] (6) and trans-[RuCl2(cod)(EtHNCH2CH2NHEt)] (7) in high yields. The presence of N-H functionalities in the coordinated diamine ligands of 6 and 7 was unambiguously established by single-crystal X-ray diffraction studies. The dealkylation process of the teeda ligand seems to proceed intramolecularly as shown by solution NMR studies performed with the soluble Ru(II) precursors trans-[RuCl2(amine)2(diene)] (diene = nbd, amine = morpholine, 9; diene = cod, amine = Et2NH, 10). The above complexes [RuCl2(diene)(diamine)] have been tested as precatalysts in the hydrogenation of ketones both for transfer as well as direct hydrogenation, the latter route being the most effective.     

Experimental and Computational Investigations of the Reactions between α,β-Unsaturated Lactones and 1,3-Dienes by Cooperative Lewis Acid/Brønsted Acid Catalysis

The reactions of α,β-unsaturated δ-lactones with activated dienes such as 1,3-dimethoxy-1-[(trimethylsilyl)oxy]-1,3-butadiene (Brassard's diene) are barely known in literature and show high potential for the synthesis of isocoumarin moieties. An in-depth investigation of this reaction proved a stepwise mechanism via the vinylogous Michael-products. Subsequent cyclisation and oxidation by LHMDS and DDQ, respectively, provided six mellein derivatives (30–84 %) and four angelicoin derivatives (40–78 %) over three steps. DFT-calculations provide insights into the reaction mechanism and support the theory of a stepwise reaction.     

Lewis base activation of Lewis acids. Vinylogous aldol addition reactions of conjugated N,O-silyl ketene acetals to aldehydes

N,O-Silyl dienyl ketene acetals derived from unsaturated morpholine amides have been developed as highly useful reagents for vinylogous aldol addition reactions. In the presence of SiCl4 and the catalytic action of chiral phosphoramide (R,R)-3, N,O-silyl dienyl ketene acetal 8 undergoes high-yielding and highly site-selective addition to a wide variety of aldehydes with excellent enantioselectivity. Of particular note is the high yields and selectivities obtained from aliphatic aldehydes. Low catalyst loadings (2-5 mol %) can be employed. The morpholine amide serves as a useful precursor for further synthetic manipulation.     

A simple route to novel functionalized tetrathiafulvalene vinylogues

The synthesis and X-ray structural determination of vinylogous tetrathiafulvalenes (TTFV) bearing functional groups on the central conjugation are reported. An unexpected evolution of the bis hydroxymethyl TTFV leading to a derivative, which acts simultaneously as a diene and a dienophile in a Diels-Alder reaction is also described.     

Recent progress on direct catalytic asymmetric vinylogous reactions

Direct catalytic asymmetric vinylogous reaction serves as a powerful tool to introduce stereocenter(s) at the γ- or/and even more remote position(s) of the vinylogous products in an atom-economical and efficient way. A variety of direct catalytic asymmetric vinylogous reactions with broad substrate scope and mild reaction conditions has been developed. Both metal catalysis and organocatalysis contributed in this field and led to the vinylogous products in high stereoselectivity. These vinylogous reactions provided efficient pathways for the synthesis of highly functionalized optically pure compounds, especially these with potential biological activity and pharmacological activity. This digest paper mainly focuses on the most recent developments in this field, including both nucleophilic addition and nucleophilic substitution.     

Diastereoselective synthesis of a novel lactam peptidomimetic exploiting vinylogous Mannich addition of 2-silyloxyfuran reagents

The total synthesis of a potential inhibitor of HIV-protease—the chiral nonracemic six-membered hydroxy lactam 6—has been accomplished, that involves, as key reaction, the highly diastereoselective vinylogous Mannich addition of furan-based silyloxy diene 7 to glyceraldeyde imine 8.     

High-pressure Diels-Alder approach to natural kainic acid

The first Diels-Alder based synthesis of (-)-kainic acid is described. Danishefsky's diene and a vinylogous malonate derived from 4-hydroxyproline combine under high pressure to afford a key bicyclic intermediate with virtually no loss of enantiopurity. This adduct can be converted into the natural product with complete stereocontrol. [reaction: see text].     

Tandem nucleophilic addition/fragmentation reactions and synthetic versatility of vinylogous acyl triflates

A thorough analysis of the chemistry of vinylogous acyl triflates provides insight into important chemical processes and opens new directions in synthetic technology. Tandem nucleophilic addition/C-C bond cleaving fragmentation reactions of cyclic vinylogous acyl triflates 1 yield a variety of acyclic acetylenic compounds. Full details are disclosed herein. A wide array of nucleophiles, such as organolithium and Grignard reagents, lithium enolates and their analogues, hydride reagents, and lithium amides, are applied. The respective reactions produce ketones 2, 1,3-diketones and their analogues 3, alcohols 4, and amides 5. The present reactions are proposed to proceed through a 1,2-addition of the nucleophile to the carbonyl group of starting triflates 1 to form tetrahedral alkoxide intermediates C, followed by Grob-type fragmentation, which effects C-C bond cleavage to yield acyclic acetylenic compounds 2-5 and 7. The potent nucleofugacity of the triflate moiety is channeled through the sigma-bond framework of 1, providing direct access to the fragmentation pathway without denying other typical reactions of cyclic vinylogous esters. The synthetic versatility of vinylogous acyl triflates, including functionalization reactions of the cyclic enone core (1 --> 6 or 8), is also illustrated.     

On the Functional Group Tolerance of Ester Hydrogenation and Polyester Depolymerisation Catalysed by Ruthenium Complexes of Tridentate Aminophosphine Ligands

The synthesis of a range of phosphine‐diamine, phosphine‐amino‐alcohol, and phosphine‐amino‐amide ligands and their ruthenium(II) complexes are reported. Five of these were characterised by X‐ray crystallography. The activities of this collection of catalysts were initially compared for the hydrogenation of two model ester hydrogenations. Catalyst turnover frequencies up to 2400 h^?1 were observed at 85 °C. However, turnover is slow at near ambient temperatures. By using a phosphine‐diamine Ru^II complex, identified as the most active catalyst, a range of aromatic esters were reduced in high yield. The hydrogenation of alkene‐, diene‐, and alkyne‐functionalised esters was also studied. Substrates with a remote, but reactive terminal alkene substituent could be reduced chemoselectively in the presence of 4‐dimethylaminopyridine (DMAP) co‐catalyst. The chemoselective reduction of the ester function in conjugated dienoate ethyl sorbate could deliver (2E,4E)‐hexa‐2,4‐dien‐1‐ol, a precursor to leaf alcohol. The monounsaturated alcohol (E)‐hex‐4‐en‐1‐ol was produced with reasonable selectivity, but complete chemoselectivity of C?O over the diene is elusive. High chemoselectivity for the reduction of an ester over an alkyne group was observed in the hydrogenation of an alkynoate for the first time. The catalysts were also active in the depolymerisation reduction of samples of waste poly(ethylene terephthalate) (PET) to produce benzene dimethanol. These depolymerisations were found to be poisoned by the ethylene glycol side product, although good yields could still be achieved.     

Functionalization and Rearrangement of Spirocyclohexadienyl Oxindoles: Experimental and Theoretical Investigations

The preparation and functionalization of spirocyclohexa‐2,5‐diene oxindoles is described. The spirocyclic core of the title compounds was installed by using a SmI₂‐mediated cyclization of aryl iodobenzamides. Epoxidation with CF₃CO₃H was then carried out and was shown to occur with a high level of diastereocontrol: the reagent approaches the diene moiety syn to the amide group, which is likely to be as a consequence of hydrogen bonding between the amide C?O bond and the peracid hydrogen. Carbanionic functionalization of the spirocyclohexa‐2,5‐diene oxindoles was then examined, leading to an unprecedented rearrangement of the strained spiro system into dearomatized phenanthridinones. Upon treatment with lithium diisopropylamide (LDA) at ?40 °C, the dienes rearranged to provide a phenanthridinone lithium enolate intermediate that was trapped by electrophiles including alkyl halides and aldehydes. Interestingly, alkylation and hydroxyalkylation occurred with different regiocontrol. DFT calculations were performed that rationalize the observed skeleton rearrangement, emphasizing the role of LDA/diisopropylamine in this rearrangement. The proposed mechanism thus relies on a thermodynamically driven diisopropylamine‐mediated proton transfer with the cleavage of the diene–amide C?O bond as the key step.     

Direct vinylogous Mannich-type reactions via ring opening and rearrangement of vinyloxiranes

[reaction: see text] The first synthetic application of 2-methyl-2-vinyloxirane as a masked dienolate has been successfully demonstrated in the direct vinylogous Mannich-type reaction with an alpha-imino ester as an electrophile. The Mannich adduct was a useful intermediate en route to cis-5-substituted pipecolinic acid ethyl ester under simple hydrogenation conditions.