Cobalt(I)-mediated preparation of polyborylated cyclohexadienes: scope, limitations, and mechanistic insight

A series of 1,3- and 1,4-diboryl-1,3-cyclohexadienes have been prepared by intermolecular CoCp-mediated [2+2+2] cocyclizations of alkynylboronic pinacolate esters with alkenes, followed by oxidative demetallation with iron(III) chloride. The effect of substitution at the borylated alkyne on chemo- and regioselectivities has been studied, suggesting steric control. The proper choice of substituents allowed the preparation of 1,3-diborylated cyclohexadienes in a highly selective manner. Alternatively, 1,4-diborylated cyclohexadienes could be prepared from diborylated diynes. The scope of this reaction has been examined and found to include electron-poor, electron-rich, linear, and cyclic alkenes. The diborylated cyclohexadienes were submitted to single or double Suzuki-Miyaura cross-coupling reactions with haloarenes to afford polyarylated systems. The mechanism of the title reaction, including the regioselectivity of the cycloaddition steps, has been analyzed by means of DFT computations.     

Radical dearomatization of benzene leading to phenanthridine and phenanthridinone derivatives related to (±)-pancratistatin

The synthesis of the phenanthridinone nucleus common to the Amaryllidaceae series of natural products is achieved by a sequence involving tributylstannane-mediated, benzeneselenol-catalyzed addition of ortho-nitrogen functionalized aryl radicals to benzene, yielding aryl-substituted cyclohexadienes. These cyclohexadienes may be manipulated by oxidative ring closure sequences to generate functionalized phenanthridines. Beginning from 2-hydroxy-6-iodopiperonic acid a key intermediate in the Danishefsky synthesis of (±)-pancratistatin is achieved in two steps.     

Sequential Birch reaction and asymmetric Ir-catalyzed hydrogenation as a route to chiral building blocks

A range of 1,2,4-trisubstituted cyclohexadienes obtained from the Birch reaction were hydrogenated asymmetrically to produce synthetically valuable chiral compounds in high enantio- and diastereoselectivity.     

1,4‐Cyclohexadienes—Easy Access to a Versatile Building Block via Transition‐Metal‐Catalysed Diels–Alder Reactions

1,4‐Cyclohexadiene derivatives are easily accessed via transition‐metal cycloadditions of 1,3‐dienes with alkynes. The mild reaction conditions of several transition‐metal‐catalysed reactions allows the incorporation of various functional groups to access functionalised 1,4‐cyclohexadienes. The control of the regiochemistry in the intermolecular cobalt‐catalysed Diels–Alder reaction is realised utilising different ligand designs. The functionalised 1,4‐cyclohexadiene derivatives are valuable building blocks in follow‐up transformations. Finally, the oxidation of the 1,4‐cyclohexadienes can be accomplished under mild conditions to generate the corresponding arene derivatives.     

Discrimination of the Enantiotopic Faces of Structurally Unbiased Carbenium Ions Employing a Cyclohexadiene-Based Chiral Hydride Source

An enantioselective reduction of simple carbenium ions with cyclohexadienes containing a hydridic C−H bond at an asymmetrically substituted carbon atom is disclosed. The net reaction is a transfer hydrogenation of alkenes (styrenes) only employing chiral cyclohexadienes as dihydrogen surrogates. The trityl cation is used to initiate a Brønsted acid-promoted process, in which a delicate intermolecular capture of a carbenium-ion intermediate by the aforementioned chiral hydride source is enantioselectivity determining. Exclusively non-covalent interactions are rendering one of the transition states energetically more favored, giving the reduction products in good enantiomeric ratios. The computed reaction mechanism supports the present findings as well as previous results obtained from studies on other transfer-hydrogenation methods involving the cyclohexadiene platform.     

Unusual gold(I)-catalyzed isomerization of 3-hydroxylated 1,5-enynes: highly substrate-dependent reaction manifolds

[reaction: see text] The gold(I) isomerization of diversely substituted 3-hydroxylated enynes has led to the discovery of three new unreported skeletal rearrangements furnishing structures such as alkylidene-cyclopentenes, cyclohexadienes or alpha,beta-unsaturated aldehydes under very mild conditions.     

Desymmetrization of metallated cyclohexadienes with chiral N-tert-butanesulfinyl imines

This communication describes the desymmetrization of various achiral metallated cyclohexadienes with a series of chiral N-tert-butanesulfinyl imines. Depending on the metal used, either the symmetrical diene (dicyclohexadienyl-zinc) or the desymmetrized diene (cyclohexadienyl-MgCl) is obtained in a good regioselectivity with excellent diastereoselectivity. The products formed should be useful building blocks for natural product synthesis. The symmetrical 1,4-dienes are readily oxidized to the corresponding diarylmethylamine derivatives.     

Tandem 1,4-addition reactions with benzene and alkylated benzenes promoted by pentaammineosmium(II)

Electrophiles such as dimethoxymethane and 3-penten-2-one react with the complex [Os(NH(3))(5)(eta(2)-benzene)](2+) in the presence of triflic acid to form metastable benzenium intermediates. These benzenium intermediates further react with carbon nucleophiles including silyl ketene acetals, (silyloxy)alkenes, and phenyllithium in an overall tandem 1,4-addition sequence. The metal fragment controls the relative stereo- and regiochemistry for both electrophilic and nucleophilic addition steps. Upon oxidative demetalation with silver triflate, cis-1,4 cyclohexadienes are formed in yields ranging from 16 to 82%. This methodology can also be used to dearomatize toluene and ortho- and meta-xylene with unexpectedly high regio- and stereocontrol.     

Theoretical insights into the [4 + 2]/retro [4 + 2] cycloaddition approach to the synthesis of biaryls and polycyclic aromatics

A domino [4+2]/retro [4+2] cycloaddition process of cyclohexadienes with arylethynes or benzyne providing access to biaryls and polycyclic aromatics has been studied theoretically using density functional theory calculations. It has been found that the initial Diels-Alder (D-A) reaction acts as the rate-determining step and the consequent [4+2] cycloreversion reaction is feasible under the conditions used. Furthermore, the D-A reaction affects the regioselectivity, the origin of which is essentially derived from the good match of orbital coefficients between dienes and dienophiles as shown by using frontier molecular orbital (FMO) theory. Further investigation of the reactivity reveals that the reactions are predicted to fail to occur if an electron-donor group in the diene or an electron-acceptor group in the dienophile is lacking, as a consequence of the increased FMO energy gap. By further exploring the scope of substrates computationally, benzyne as an active dienophile was predicted to react with a variety of dienes in a cascade reaction under mild conditions with a low energy barrier, with the rate-determining step being the retro [4+2] cycloaddition.     

Catalytic One-Pot Osmylation of Cyclohexadienes: Stereochemical and conformational studies of the resulting polyols

Catalytic double osmylation is described for a series of cyclohexadienes in acetone/H₂O in the presence of the co-oxidant N-methylmorpholine N-oxide (NMO). The formation of polyols occurred stereospecifically with cyclohexadienes 3,7 , and 11a , leading thereby to tetrols 5a , and 9a and to allo-inositol ( 14a ), respectively. To the contrary, trans-cyclohexadiene-diol 15a gave a mixture of the stereoisomeric inositols 18a (epi), 19a (neo), and 20a (chiro). High-field NMR let to clearcut conformational analyses of the polyhydroxylated derivatives.     

Preparations,structures and reactions of mono-alkene alkyne complexes of rhodium(I): The crystal structures of acetylacetonato(ethylene) (hexafluorobut-2-yne)rhodium(I) and acetylacetonato(cyclo-octene) (hexafluorobut-2-yne)rhodium(I)

Mono-alkene alkyne complexes of rhodium(I) have been synthesised, and characterised by i.r., ¹⁹F n.m.r., and crystallography. Their role as intermediates in the formation of cyclohexadienes is described.     

Silylated cyclohexadienes as new radical chain reducing reagents: preparative and mechanistic aspects

Various silylated 1,4-cyclohexadienes are presented as superior tin hydride substitutes for the conduction of various radical chain reductions. Debrominations, deiodinations, and deselenations can be performed using these environmentally benign reagents. Furthermore, Barton-McCombie-type deoxygenations using silylated cyclohexadienes are described. Radical cyclizations, ring expansions, and Giese-type addition reactions with the new tin hydride substitutes are presented. The polymerization of styrene can be regulated using silylated cyclohexadienes. Rate constants for hydrogen atom abstraction from two 1-silyl-cyclohexadienes by primary C-radicals were determined. The effects of the cyclohexadiene substituents on the reaction outcomes are discussed. Finally, qualitative EPR experiments on silyl radical expulsion from silylated cyclohexadienyl radicals are presented.     

The Condensation of Cyclic Aminoketones,Cyclohexanone and Cyclohexane-1,4-dione with some Phenolic Ethers in Polyphosphoric Acid

The title condensations gave respectively: gem-bisarylated cyclic amines 3a–k or monoarylated unsaturated cyclic amines 4a–g , 1,3-bisarylated cyclohexadienes 6a , 6b , the condensed bicyclo [2,2,2]-octane 8 . In addition the aromatic ketone 9 gave the fluorenone 10 on treatment with polyphosphoric acid (PPA).     

Silylated Cyclohexadienes in Radical Chain Hydrosilylations

A new method for the mild radical hydrosilylation of alkenes and alkynes is described. Silylated cyclohexadienes that can be readily prepared on large scale are used as radical hydrosilylating reagents. Non‐activated alkenes and alkynes are hydrosilylated in high yields. The reaction can be combined with C C bond formation, as demonstrated for the preparation of silylated cycloalkanes from the corresponding dienes. Furthermore, radical hydrosilylations in combination with β‐fragmentation reactions for the synthesis of allylsilanes and hydrosilylations of aldehydes and ketones providing protected alcohols can be readily performed by this strategy.     

Carbolithiation of aromatic rings: cyclohexadienes from N-aroyl-2,2,6,6-tetramethylpiperidines

Benzamides whose nitrogen atom is part of a 2,2,6,6-tetramethylpiperidine ring are dearomatised by alkyllithiums, which attack them regioselectively to yield, after electrophilic quench, substituted cyclohexadienes.     

Ring synthesis by stereoselective, methylene-free enyne cross metathesis

Tandem enyne metathesis between 1-alkynes and 1,5-cyclooctadiene or all-cis-1,4-polybutadiene resulted in a direct, one-step ring synthesis of cyclohexadienes by methylene-free metathesis. The use of methylene-free metathesis conditions provided apparent Z-selectivity in the intermolecular enyne metathesis step.     

Au- and pt-catalyzed cycloisomerizations of 1,5-enynes to cyclohexadienes with a broad alkyne scope

We describe the development of gold- and platinum-catalyzed cycloisomerizations of 1,5-enynes. This catalytic process displays a wide alkyne scope and furnishes a range of highly functionalized 1,4- and 1,3-cyclohexadienes. In the case of 1-siloxy-1-yne-5-enes, the reactions are efficiently catalyzed by AuCl (1 mol %) at ambient temperature to afford siloxy cyclohexadienes or the corresponding 1,2- and 1,3-cyclohexenones upon subsequent protodesilylation. We propose that the reaction proceeds via a novel mechanism involving a series of 1,2-alkyl shifts. Elucidation of this unusual reaction mechanism enabled us, in turn, to significantly expand the scope of the cycloisomerization by incorporation of a quaternary center at the C(3) position of the enyne. Indeed, we established that PtCl(2) (5 mol %) efficiently catalyzed the cycloisomerizations of 1,5-enynes containing terminal, internal, and arene-conjugated alkynes. Since a variety of 1,5-enynes are readily accessible, the cycloisomerization provides a rapid approach to a wide range of highy substituted cyclohexadienes for many subsequent synthetic applications.     

Tandem Michael addition/ylide olefination reaction for the synthesis of highly functionalized cyclohexadiene derivatives

A tandem Michael addition/ylide olefination for the rapid creation of highly functionalized cyclohexadiene is developed. The tandem annulation reactions afford versatile cyclohexadienes in good to excellent isolated yields. This method has been successfully applied to the synthesis of three biologically active molecules.     

Transformations of benzene-argon mixture in barrier discharge

The transformation of a benzene-argon mixture in dielectric-barrier discharge (DBD) was studied. Benzene-soluble polymeric compounds (76.5 wt %), biphenyl (7.6 wt %), and phenylcyclohexadienes (9 wt %) are the major products. Monoalkylbenzenes, cyclohexadienes, and ethynylbenzene are in trace amounts in the reaction mixture. The benzene conversion per pass through the discharge zone was 5.5 wt %. The possible mechanism of the benzene transformation in DBD was suggested on the basis of experimental data and theoretical calculations.     

Synthetic Studies on Damascenones

The odor principle β-damascenone and its isomer α-damascenone have been prepared by treatment of the corresponding ethyl safranates with excess allyl lithium followed by alkoxide catalyzed isomerization of the resulting products with β, γ-unsaturated ketonic side chains. Addition of allyltriphenylphosphorane (preferably prepared from allyltriphenylphosphonium chloride) rather than the propenyl isomer to ethyl α-isopropylidene-acetoacetate produced ethyl α-safranate. This represents a new, potentially general method for the synthesis of functionalized cyclohexadienes.