Transannular Cyclization Research Articles

ChemInform Abstract: New Control Possibilities of the Transannular Cyclization of 1,5- Dienes, for Example of Methyl-cis-bicyclo(4.3.0)nona-3,7-dienes, in the Ritter Reaction.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Tandem Cyclization-Cycloaddition Reaction of Rhodium Carbenoids. Studies Dealing with the Geometric Requirements of Dipole Formation.

The carbenoid intermediate derived by the treatment of several 1-diazobutanediones with rhodium(II) acetate undergoes ready transannular cyclization onto the neighboring keto group to give five-membered ring carbonyl ylides. The dipole derived from ethyl 4-diazo-2-methyl-3-oxobutyrate was found to undergo a rapid proton transfer, producing 5-ethoxy-4-methyl-3-(2H)-furnone. When the position adjacent to the diazo carbonyl group is blocked with two substituent groups, however, smooth 1,3-dipolar cycloaddition occurs. The observed regioselectivity can be nicely accomodated in terms of frontier molecular orbital (FMO) theory. A type II FMO interaction is involved since carbonyl ylides possess one of the smallest HOMO-LUMO energy gaps of common 1,3-dipoles. The rhodium(II)-catalyzed reaction of 1-diazo-6-phenyl-2,6-hexanedione afforded a mixture of products. In addition to the expected cycloadduct, a product derived from the bimolecular addition of the rhodium carbenoid to benzene was obtained

ChemInform Abstract: Friedel-Crafts Transannular Alkylation of Aromatic Compounds with Nonconjugated Cyclic Dienes.

Friedel–Crafts transannular alkylation of aromatic compounds with nonconjugated cyclic dienes such as (Z,Z)-1,5-cyclooctadiene (1,5-COD), bicyclo[2.2.1]hepta-2,5-diene (norbornadiene), and 1,4-cyclohexadiene was studied. The five to six isomers of phenylbicyclooctanes were produced in the alkylation of benzene with 1,5-COD in the presence of either Bronsted acid or Lewis acid as the catalyst. The isomer ratios depended on the nature and the amount of catalyst, the reaction time, and the reaction temperature. In the AlCl3-catalyzed reaction of 1,5-COD with toluene it was disclosed that an initial para-rich isomer distribution of the products shifted to a meta-rich one in a prolonged reaction. With norbornadiene a transannular cyclized compounds was obtained, while with 1,4-cyclohexadiene no transannular cyclization was observed.

ChemInform Abstract: First Synthesis of the Trinervitane System from Secotrinervitane by Transannular Ring Construction.

The unique skeleton of the tricyclic diterpene, trinervitane, was synthesized for the first time in racemic form by a transannular cyclization of a secontrinervitane derivative.

The Chemical Behavior of 3,4‐Benzocycloocten‐1,5‐diyne

AbstractThe title compound 3,4‐benzocycloocten‐1,5‐diyne (1) is a highly reactive hydrocarbon that has been shown to undergo addition reactions with tetraphenyl‐cyclopentadienone(tetracyclone) to the 2:1 adduct 6, with octacarbonyldicobalt to the bis metal complex 7, with lithium aluminium hydride to the bis diene 9, and with various electrophilic reagents. In these latter cases cationic intermediates are generated from 1 and a transannular cyclization takes place leading to novel derivatives of 1,2‐dihydropentalene (31, 32, 35, 36, 43, 44).

Can π6 + π4 = 10? Exploring Cycloaddition Routes to Highly Unsaturated 10-Membered Rings

This paper uses DFT and G3(MP2) calculations to examine whether unbridged 10-membered rings can be made by (pi)6 + (pi)4 cycloadditions to (Z)- and (E)-hexatrienes, hexa-1,5-dien-3-ynes, (Z)-hexa-1,3-dien-5-ynes, hexa-1,2,3,5-tetraenes, and (Z)-hexa-3-ene-1,5-diynes. Cycloadditions to four 4pi reactants, buta-1,3-diene, butenyne, butatriene, and butadiyne, are explored. Thirty different basic cycloadditions are identified, and all are shown to be exothermic according to G3(MP2) calculations; strain energies in the products are comparable with that of cyclodecane itself, despite the presence of trans-alkene, alkyne, allene, cumulene, and s-trans diene moieties. The major obstacles to the isolation of 6 + 4 cycloaddition products are competing (pi)4 + (pi)2 cycloadditions and, especially, rapid Cope rearrangement of the products, but, in many cases, the judicious introduction of substituents can overcome these problems so that practical syntheses should be possible. Reactions between (E)-hexa-1,3,5-triene and s-trans-buta-1,3-diene are shown to have substantially lower activation energies than those involving (Z)-hexa-1,3,5-triene reacting with either s-cis- or s-trans-buta-1,3-diene. Conformationally locked derivatives of s-cis,s-cis (E)-hexa-1,3,5-trienes can lead to derivatives of (Z,Z,E)-cyclodeca-1,3,7-triene that are stable to Cope rearrangement, and reactions should proceed at close to ambient temperatures with suitable activating groups. We predict that it should be possible to prepare suitably substituted derivatives of at least 11 more highly unsaturated ring systems: (5Z,7Z)-cyclodeca-1,2,5,7-tetraene, (1Z,3Z)-cyclodeca-1,3-dien-7-yne, (2Z,7E)-cyclodeca-1,2,3,7-tetraene, (Z)-cyclodeca-1,2,3-trien-7-yne, (4Z,8E)-cyclodeca-1,2,4,8-tetraene, (Z)-cyclodeca-1,2,4,5,7-pentaene, (Z)-cyclodeca-1,2,4-trien-8-yne, (1Z,7E)-cyclodeca-1,7-dien-3-yne, (R,S,E)-cyclodeca-1,2,4,5,8-pentaene, cyclodeca-1,2,4,5,8,9-hexaene, and (R,S)-cyclodeca-1,2,4,5-tetraen-8-yne. In three other cases, we predict that cycloaddition will be followed by unusual and intriguing rearrangements. Cycloadditions can be accelerated by the presence of electron-withdrawing groups in either the 6pi or 4pi reactants. Transannular cyclizations of some products may lead to interesting stereocontrolled routes to 6,6- and/or 5,7-bicyclic structures.

Conformational Properties of the Germacradienolide 6-Epidesacetyllaurenobiolide by Theory and NMR Analyses

Knowing the conformational properties of 1(10),4-cyclodecadiene gamma-lactones is important because of the biogenetic and evolutionary implications on the different groups of sesquiterpene lactones. Despite their importance, there are no physicochemical data on the conformational dynamic and the potential energy surface associated with the conformational changes of the cyclodecadiene ring. Fischer's biogenetic theory on the origin of ambrosanolides and helenanolides has support in the results presented since the conformers that yield two groups of sesquiterpene lactones coexist in solution as demonstrated by dynamic NMR experiments. These results are important on the basis of Fischer's proposal that states that the biosynthesis of each group of pseudoguaianolides requires a specific enzyme to select the right conformer to start the electrophilic cyclization. The germacra-1(10),4-dien-12,8alpha-olides can exist as a mixture of four different conformations, [(15)D(5),(1)D(14)], [(15)D(5),(1)D(14)], [(15)D(5),(1)D(14)], and [(15)D(5),(1)D(14)], and it is also proposed that the configuration of trans-annular cyclization depends on the conformation of the precursor. The results of the study presented herein show that 6-epi-desacetyllaurenobiolide exists in solution at room temperature as a mixture of two stable conformers, [(15)D(5),(1)D(14)] and [(15)D(5),(1)D(14)], which are more stable due to the diminishing of the so-called allylic strain. Analysis of the potential energy surface associated with the conformational interchange showed two other conformers that are intermediaries in the equilibria between [(15)D(5),(1)D(14)]/[(15)D(5),(1)D(14)] and [(15)D(5),(1)D(14)]/[(15)D(5),(1)D(14)]. This indicates the presence of six different conformers participating in the global process instead of the four that have been proposed. The experimental values of DeltaH(++), DeltaG(++), DeltaH(conf), and DeltaG(conf) of the conformational exchange and those calculated at the mPW1B95/6-31+G(d,p) level of theory are very similar, indicating that such level of theory is adequate for the description of this conformational equilibrium.

Reaction of Cage-opened Fullerene Derivative with Grignard Reagents and Subsequent Transannular Cyclization

Abstract 1,2-Addition of methyl and allyl Grignard reagents to a cage-opened fullerene derivative 2a selectively proceeded at −20 °C in THF at one of the two carbonyl groups. Under acidic conditions, the resulting alcohol underwent a transannular cyclization. The elevated LUMO levels of these products were shown by electrochemical and theoretical investigations.

Enantiospecific Synthesis of the Cubitane Skeleton

The fully substituted 12-membered macrocycle of the cubitane-type diterpenoids has been assembled in an enantioselective manner following a novel "bridge-and-cut" strategy. Hydroxyalkylation of (S)-carvone afforded a carvonylgeraniol, which underwent transannular cyclization on treatment with samarium diiodide in THF. Fragmentation of one of the shorter bridges of the resulting [8.2.2]bicycle liberated the 12-membered ring with the desired cis-arrangement of the isopropenyl side chains.

Polyprenylated Benzoylphloroglucinol-Type Derivatives Including Novel Cage Compounds from <i>Hypericum erectum</i>

Hyperici erecti herba (Hypericum erectum THUNB.) showed a suppressive effect on generation of isovaleric acid by Corynebacterium xerosis. An ethyl acetate (AcOEt) soluble fraction of methanol extract of H. erectum showed the activity. The AcOEt fraction was separated by various successive choromatographical methods to give seven new compounds 1-7 along with some known compounds. The structures of the new compounds were elucidated to be polyprenylated benzoylphloroglucinol derivatives by means of HR-MS and NMR spectra including 2D-NMR. Some of these compounds had novel cage structures having benzoyltricyclo[3,3,1,1(3,7)]decane and benzoyltricyclo[4,3,1,1(3,8)]undecane skeletons arising from a polyprenylated phloroglucinol precursor by a transannular cyclization reaction. The isolated compounds were tested for suppressive activity, but they showed only weak activity.

The reactions of 3,7-dimethylenebicyclo[3.3.1]nonane, norbornadiene and cis, cis-1,5-cyclooctadiene with pentafluoro-λ 6-sulfanyl chloride

Radical transannular cyclizations of the non-conjugated dienes, such as 3,7-dimethylenebicyclo[3.3.1]nonane and norbornadiene with SF 5Cl upon UV-irradiation led to the corresponding SF 5-substituted 3,7-noradamantane and nortricyclanes with high yields. Radical reaction of cis, cis-1,5-cyclooctadiene with SF 5Cl led to a product of SF 5Cl addition to one of the diene double bonds either UV-irradiation or triethylborane were used for radical initiation.

A Concise Synthesis of Castanospermine by the Use of a Transannular Cyclization

A nine-step synthesis of (+)-castanospermine has been accomplished in 22% overall yield from methyl alpha-D-glucopyranoside. The key transformations involve a zinc-mediated fragmentation of benzyl-protected methyl 6-iodoglucopyranoside, ring-closing olefin metathesis, and strain-release transannular cyclization to afford the indolizidine skeleton of the natural product.

New Pathways in Transannular Cyclization of Germacrone [Germacra-1(10),4,7(11)-trien-8-one]: Evidence Regarding a Concerted Mechanism

The transannular cyclization of germacrone with HSO(3)Cl at -78 degrees C by means of a concerted and regioselective mechanism gives rise to a bicyclo[6.2.0]decan-2-ylium intermediate ion, which evolves to unusual skeletons through subsequent cyclization and Wagner-Meerwein rearrangements. This novel germacra-1(10),4-diene cyclization could suggest the existence of a new biosynthetic pathway to sesquiterpenes.

Direct synthesis of medium-bridged twisted amides via a transannular cyclization strategy.

The sequential RCM to construct a challenging medium-sized ring followed by a transannular cyclization across a medium-sized ring delivers previously unattainable twisted amides from simple acyclic precursors.

Synthesis of 5-tert-butyl-8,12,14-trimethyl- and 5-tert-butyl-8,12,14,16-tetramethyl[2.2]metacyclophane and their treatment with Lewis acids in benzene

Treatment of 5- tert-butyl-8,12,14,16-tetramethyl[2.2]MCP with AlCl3-MeNO2 in benzene led to trans- tert-butylation to afford 8,12,14,16-tetramethyl[2.2]MCP in good yield along with tert-butylbenzene. On the other hand, the same treatment of 5- tert-butyl-8,12,14-trimethyl[2.2]MCP led to transannular cyclisation reaction and isomerisation reaction to afford the corresponding strainless 2- tert-butyl-3a,6,8-trimethyl-3,3a,4,5,9,10-hexahydropyrene in good yield.

ChemInform Abstract: Germacrenes A—E and Related Compounds: Thermal, Photochemical and Acid Induced Transannular Cyclizations

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Reaction Discovery Employing Macrocycles: Transannular Cyclizations of Macrocyclic Bis-lactams

Macrocyclic bis-lactams have been synthesized by cyclodimerization of homoallylic amino esters employing a Zr(IV)-catalyzed ester-amide exchange protocol. Base-mediated transannular cyclizations have been identified to access both bicyclic [5-11] and tricyclic [5-8-5] frameworks in good yield and diastereoselectivity. Preliminary mechanistic studies support an olefin isomerization-intramolecular conjugate addition pathway.

Ti-catalyzed transannular cyclization of epoxygermacrolides. Synthesis of antifungal (+)-tuberiferine and (+)-dehydrobrachylaenolide

We present a divergent strategy for the stereoselective synthesis of both eudesmanolides (+)-tuberiferine and (+)-brachylaenolide starting from the accessible germacrolide (+)-costunolide. The key steps of these syntheses are the Ti-catalyzed transannular cyclization of a 1,4-epoxygermacrolide in the presence or absence of water, respectively. The catalytic cycle operating in the presence of water probably involves the reduction of a tertiary radical by H-atom transfer from aquacomplex Cp 2Ti III(OH 2)Cl. The catalytic cycle under anhydrous conditions presumably occurs through mixed disproportionation between a tertiary radical and Cp 2Ti IIICl. Synthetic (+)-tuberiferine and (+)-brachylaenolide displayed an antifungal potency against Phycomyces blakesleeanus comparable or even higher than amphotericin B, the gold standard for antifungal therapy.

Substituent effects in the transannular cyclizations of germacranes. Synthesis of 6- epi-costunolide and five natural steiractinolides

The occurrence and orientation of substituents in the 10-membered ring characteristic of germacranes is determinant in the stereochemical outcome of the acid-promoted transannular cyclization of these metabolites. An explanation of the synthesis of eudesmanolides and guaianolides produced by the Umbelliferae family of plants is advanced. The syntheses of the natural products 6- epi-costunolide and five steiractinolides are reported.

Stereocontrolled Formal Synthesis of (±)-Platensimycin

The caged structure of platensimycin, known as Nicolaou's key intermediate for total synthesis of platensimycin, was synthesized stereoselectively by using the following key steps: (i) diastereoselective Diels-Alder reaction between gamma-benzoyloxy enone and tert-butyldimethylsiloxydiene, (ii) formation of a dihydropyran ring by intramolecular catalytic oxypalladation, and (iii) transannular radical cyclization of monothioacetal with tributyltin hydride and AIBN.