Seven-membered Carbocycle Research Articles

Fused Seven-Membered Carbocycle Construction through Electrochemical Relay Cyclization.

Seven-membered carbocycles, which are frequently associated with relevant biological activities, can be found in nature and drugs in ever-increasing numbers. Radical cascade addition of 1,n-enynes-like substrates is one of the most important and efficient strategies for the synthesis of this valuable skeleton with structural diversity and complexity. Herein, we describe an electrooxidative radical-mediated synthesis of dibenzocycloheptanes from ortho-ethynyl-substituted biaryls and tertiary C(sp3)-H containing reactants. The chemo- and regioselective addition of in situ generated carbon radical onto the alkynyl moieties triggers a desired reaction cascade, resulting in the formation of three new C-C bonds. This approach provides a step-economical regime for the facile assembly of a wide range of polycyclic products containing a 6-7-5 system. This green strategy features a good substrate scope, mild conditions, and high efficiency under ferrocene-mediated electrochemical oxidation conditions.

Synthesis of 2,2′-biphenyl-fused porphyrins: Installation of directly fused seven-membered ring

2,2[Formula: see text]-Biphenyl-fused Ni(II) porphyrins were synthesized by two methods. One was oxidative fusion reaction of meso-(biphen-2-yl)-substituted Ni(II) porphyrin with the combination of 2,3-dichloro-5,6-dicyano-[Formula: see text]-benzoquinone (DDQ) and Sc(OTf)3 and the other was Pd-catalyzed intramolecular cyclization of meso-(2[Formula: see text]-chlorobiphen-2-yl)-substituted Ni(II) porphyrin. These fused products showed contorted structures owing to the installed seven-membered carbocycle(s) that were revealed by X-ray crystallographic analysis and exhibited moderately red-shifted absorption bands.

Total Synthesis and Structural Revision of the 6,11-Epoxyisodaucane Natural Sesquiterpene Using an Anionic 8π Electrocyclic Reaction.

A new synthetic strategy that forms a seven-membered carbocycle using an anionic 8π electrocyclic reaction facilitated the first total synthesis of the 6,11-epoxyisodaucane natural sesquiterpene in 9.0% yield over 10 steps in the longest linear sequence. The misassigned proposed stereochemistry was corrected by the synthesis of both the proposed structure and its C6 epimer. In addition, the 5-7-fused ring system was concisely constructed by tandem decyanation/five-membered-ring formation from an epoxynitrile.

Soluble, Thermally Stable, and Low Thermal Expansion Polyarylamides Enabled by a Seven-Membered Carbocycle

Soluble, thermally, and dimensionally stable polyarylamides have been a long-standing challenge for polymer chemists and materials scientists. Herein, we designed and synthesized a series of polyar...

Synthesis of guaipyridine alkaloids (±)-cananodine and (±)-rupestines D and G using an intramolecular Mizoroki-Heck reaction

The guaipyridine alkaloids cananodine, rupestine D and rupestine G were synthesized in six steps or less from readily available 3-(allyloxy)-2-(bromomethyl)-6-methylpyridine. Key steps in the synthesis include an enolate alkylation of the aforementioned substituted picolyl bromide and an intramolecular Mizoroki-Heck reaction to form the seven-membered carbocycle of the target compounds.

Synthesis of (±)-rupestines B and C by intramolecular Mizoroki-Heck cyclization

The total synthesis of rupestines B and C, two guaipyridine sesquiterpene alkaloids, is reported. These compounds are isolated from Artemisia rupestris L. and have structural similarities to that of cananodine, a guaipyridine alkaloid with activity against two liver cancer cell lines. The synthesis of rupestines B and C was accomplished in six steps using an intramolecular Mizoroki-Heck cyclization as the key-step to form the seven-membered carbocycle of the targets.

Synthesis of cananodine by intramolecular epoxide opening

Cananodine is a guaipyridine alkaloid with activity against liver cancer. Cananodine was synthesized using a remarkable intramolecular opening of a trisubstituted epoxide as the key step in construction of the seven-membered carbocycle of the target. The epoxide opening strategy allows all four stereoisomers of cananodine to be prepared.

A theoretical study on the palladium-catalyzed oxidative carbocyclization-alkoxycarbonylation of bisallenes to construct seven-membered carbocycles assisted by olefins.

The reaction mechanisms of the Pd(ii)-catalyzed oxidative carbocyclization-alkoxycarbonylation of bisallenes to construct seven-membered carbocycles have been theoretically investigated with the aid of density functional theory (DFT) calculations. Our calculation results account for the experimental fact that the product should be the seven-membered carbocycle P1 instead of the spiro-type product P2. Our calculations indicate that CO coordination should occur prior to the ring closing step, which determines the regioselectivity. Through investigating the corresponding natural bond orbital (NBO) charges, we find that an electron withdrawing carbonyl group would decrease the electron density and lower the activation barrier. Therefore, the regioselectivity is dominated by the electronic effect.

Heptagons in Aromatics: From Monocyclic to Polycyclic.

Heptagons in Aromatics: From Monocyclic to Polycyclic.

Synthesis of a Key Intermediate, 10-Acetyl-7-(t-butyldiphenylsilyloxymethyl)-4-methylbicyclo[5.3.0]dec-4-en-1-ol, in the Synthesis of Pseudolaric Acid A

10-Acetyl-7-(t-butyldiphenylsilyloxymethyl)-4-methylbicyclo[5.3.0]dec-4-en-1-ol was synthesized by aldol cyclization to a five-membered ring, epoxidation, samarium diiodide-induced ring opening, and the RCM reaction to the seven-membered carbocycle. This method has succeeded in constructing the desired stereochemistry in the synthesis of pseudolaric acid A.

Unexpected Prins cyclization: iron-promoted cyclization/hydration of alkynyl-dimethyl acetals

Unexpected products containing acyl-substituted unsaturated seven-membered carbocycle were synthesized by FeCl3-promoted intramolecular Prins cyclization of alkynyl-dimethylacetals in good yields. It is remarkable that the synthesized 7-exocyclic vinyl cations generated as a result of Prins-type cyclization were trapped by H2O (no halogen ion) in CH2Cl2 to give the corresponding enol derivatives. Those enol derivatives underwent enol-keto tautomerism and then eliminated one molecule of MeOH to give the corresponding acyl-substituted unsaturated seven-membered carbocycle.

Palladium-Catalyzed Synthesis of Endocyclic Allenes and Their Application in Stereoselective [2 + 2]Cycloaddition with Ketenes

Palladium-catalyzed reactions of various 2-bromo-3-exo-methylenecycloalkenes with a stabilized nucleophile were examined. When the carbocycles were nine-membered or larger, the corresponding endocyclic allenes were isolated in excellent yields. In a reaction of the eight-membered cyclic substrate, initial formation of a cycloocta-1,2-diene derivative was detected; however, it dimerized slowly. The seven-membered carbocycle was inert to the reaction. Using a chiral Pd-catalyst, an axially chiral endocyclic allene was obtained in 65% ee. The cyclic allenes were applied to [2 + 2]cycloaddition with ketenes, and the stereoselectivity was studied.

Domino intramolecular enyne metathesis/cross metathesis approach to the xanthanolides. Enantioselective synthesis of (+)-8- epi-xanthatin

The first total synthesis of (+)-8- epi-xanthatin ( 1) has been achieved in 14 steps starting from the commercially available ester 24, which was converted into aldehyde 23 in six steps. An enantioselective aldol reaction of 23 gave 30, which was transformed into triflate 22 in four steps, setting the stage for a palladium-catalyzed carbonylation reaction to form acrylate 34. Compound 34 was then subjected to a deprotection/lactonization sequence to furnish enyne 21, which underwent a domino enyne ring-closing metathesis/cross metathesis process to form a seven-membered carbocycle and ( E)-conjugated dienone, thereby completing the synthesis of 1. This domino ruthenium-catalyzed metathesis reaction thus serves as an efficient method to construct the core of xanthanolide and other sesquiterpene lactones.

A practical route to enantiopure, highly functionalized seven-membered carbocycles and tetrahydrofurans: concise synthesis of (+)-nemorensic Acid.

Highly diastereoselective thermal [5C+2C] intramolecular pyrone-alkene cycloadditions can be achieved by introducing a homochiral p-tolylsulfinyl group at a suitable position of the alkene. The resulting adducts can be readily desulfinylated to give optically active 8-oxabicyclo[3.2.1]octane derivatives. Interestingly, switching from a sulfinyl to a sulfonimidoyl group allows one to reverse the direction of the diastereofacial selectivity and thereby produces oxa-bridged carbocyclic systems enantiomeric to those obtained from the sulfinyl precursors. Cleavage of the oxa-bridge on the desulfurated adducts yields highly functionalized seven-membered carbocyclic derivatives in enantiopure form. Alternative cleavage of the seven-membered carbocycle provides enantiomerically enriched tetrahydrofurans. We have exploited this reaction pathway for the synthesis of the naturally occurring enantiomer of nemorensic acid.

Intramolecular Cyclization of (2-Functionalized Allyl)trimethylsilane with Acid Chloride. Synthesis of Two Guaianolide-Type α-Methylene γ-Lactones

Abstract α-Methylene γ -lactone fused to seven-membered carbocycle was synthesized by intramolecular cyclization of (2-ethoxycarbonylallyl)trimethylsilane or (2-acetoxymethylallyl)trimethylsilane with acid chloride. The former was found to be a better way for seven-membered carbocyclization, while the latter method was applicable to the synthesis of α- methylene γ -lactones fused to eight- and fourteen-membered carbocycles. Both guaian-8,12- and 6,12-olide type of compounds were synthesized by this method, in which the cyclization reaction proceeded stereoselectively. It was also found that both (Z)- and (E)-allylsilanes afford the same stereoisomer as the major product.

Straightforward Construction of Fused 6,7,5-Tricarbocyclic Systems by Tandem [5 + 2]/[4 + 2] Cycloadditions

One-pot coupling of an intramolecular thermal [5C + 2C] pyrone-alkene cycloaddition to a [4C + 2C] Diels-Alder reaction provides immediate access to 6,7,5-tricarbocyclic systems bearing a 1,4-oxa-bridge in the seven-membered carbocycle. The transformation entails the net formation of four carbon-carbon bonds and creates three new cycles and a minimum of five new stereocenters. Preliminary attempts to open the oxa-bridge by reaction of the adducts with samarium diiodide and trimethylsilyl triflate led to relatively unexpected deoxygenated and aromatized products.

A new type of phosphole dimer incorporating a seven-membered ring

Abstract The reaction of N -bromosuccinimide with one equivalent of the lithium derivative of the 1-phenyl-3, 4-dimethylphosphole-borane adduct ( 1 ) produces a new type of phosphole dimer ( 2 ). The X-ray crystal structure analysis shows a seven-membered carbocycle and a C α (phosphole)-CH 2 -C β (phosphole) junction.

Crystal structure 2,4-dideacetyldi-hydroxyinuchinenolide C. Effect of pseudorotation in the seven-membered ring of linear trans,trans-conjugated pseudoguanolides

The spatial structure of 2,4-dideacetyldihydroxyinuchinenolide C has been established by the x-ray structural method. On the basis of an analysis of known crystal structures of linear trans, trans-conjugated pseudoguanolides using the method of molecular mechanics it has been shown that a partial pseudo-rotation of the seven-membered carbocycle in these compounds is possible.