Acid-promoted rearrangement of drimane type epoxy compounds and their application in natural product synthesis

The reactions of (±)-α-epoxy drimenol (4) and (±)-α-epoxy drimenyl cyanide (6) with acids (proton acid or Lewis acid) selectively gave the rearranged aldehyde (±)-13 and (±)-15 having the hydroindane skeleton, respectively, while the reactions of (±)-4 and (±)-6 with Dibal-H selectively afforded the allyl alcohol (±)-14 and (±)-16, respectively. The reactions of (8aR)-6 and (8aS)-6 with Dibal-H were applied for the determination of the absolute structure of natural 7β-acetoxy-ent-labda-8(17),13(14)E-dien-15-ol (18). The reaction of (±)-α-epoxy bicyclofarnesol (5) and (8aS)-5 with proton acid selectively provided the rearranged ketol (±)- and (8aS)-31 having the hydroindane skeleton, respectively. The optically active (8aS)-31 was converted to the natural (9S)-austrodoric acid (33).     

The sulfonation of aromatic and heteroaromatic polycyclic compounds

Relative reactivities of a series of polycyclic carbo- and heteroaromatic compounds to sulfonation by sulfur trioxide in nitrobenzene are measured and discussed. The results show the following reactivity in decreasing order: indole, carbazole, pyrene, perylene, naphthalene, phenanthrene, benzene, benzothiophene, and dibenzothiophene.     

Fluoride-promoted rearrangement of organo silicon compounds: a new synthesis of 2-(arylmethyl)aldehydes from 1-alkynes

A new approach to 2-(arylmethyl)aldehydes 4 based upon a 1,2-anionotropic rearrangement of an aryl group is presented. The synthetic sequence begins with a silylformylation reaction of terminal acetylenes 5 with aryl and heteroaryl silanes 6, followed by treatment of the products (Z)-1 with TBAF. The optimization of the experimental conditions of the fluoride-promoted step is described, together with the synthetic potentialities of the process. A plausible mechanism of the rearrangement reaction is reported that suggests the addition of the fluoride ion to the arylsilicon moiety of beta-silylalkenals (Z)-1 and the consequent migration of the aryl group to the adjacent carbon atom. Both aryl and heteroaryl substituents can rearrange without any loss of configuration. Bromo-functionalized substrates undergo an intramolecular reaction that affords exclusively carbacyclobenzyl aldehydes, further enhancing the high synthetic value of this method.     

Olefin cross-metathesis for the synthesis of heteroaromatic compounds

The olefin metathesis reaction has underpinned spectacular achievements in organic synthesis in recent years. Arguably, metathesis has now become the foremost choice for a carbon-carbon double bond disconnection. Despite this general utility, de novo routes to heteroaromatic compounds using the cross-metathesis (CM) reaction have only recently emerged as an efficient strategy. This approach allows a convergent union of simple, functionalised, three- to four-carbon olefinic core building blocks, to generate furans, pyrroles and pyridines with a high degree of control of substitution pattern in the product.     

Formation of uncondensed binuclear heterocyclic compounds in the thio-claisen rearrangement of heteroaromatic sulfides

Allyl hetaryl Sulfides with an allyl fragment that is part of a heteroaromatic ring undergo a [3,3]-sigmatropic rearrangement when they are heated in various solvents, as a result of which uncondensed binuclear heterocyclic compounds are formed. On the basis of kinetic data it was shown that the inclusion of the vinyl or allyl fragment of a sulfide in the composition of the heteroaromatic ring hinders the rearrangement more, the higher the aromatic character of the heteroring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1348–1351, October, 1983.     

The synthesis of heteroaromatic nitro compounds from 3-nitrochromone

3-Nitrochromone ( 1 ) reacts with a series of nucleophiles by Michael addition followed by intramolecular condensation to yield pyrrolyl ( 2 ), phenyl ( 3 ), pyridyl ( 4 ), pyrido ( 5,6 ), pyrimidyl ( 7 ) and pyrazolyl ( 8 ) nitro derivatives. The reactions proceed under basic catalysis in 39–78% yields. Conversion of 4 to 3,4-dihydrobenzofuro[3,2-b]quinol-1-(2H)one ( 12 ) is also described. Carbon-13 data for 2, 5, 6 and 8 are discussed. The one bond C,H coupling constants in the nitropyridines are also reported and used as an analytical tool.     

Palladium-catalyzed nucleomethylation of alkynes for synthesis of methylated heteroaromatic compounds

Herein, we disclosed a novel and efficient palladium-catalyzed nucleomethylation of alkynes for the simultaneous construction of the heteroaromatic ring and methyl group. The 3-methylindoles, 3-methylbenzofurans and 4-methylisoquinolines were obtained in moderate to excellent yields. Notably, this methodology was employed as a key step for synthesis of a pregnane X receptor antagonist, zindoxifene, bazedoxifene and AFN-1252. The kinetic studies revealed that reductive elimination might be the rate-determining step.

A novel palladium-catalyzed nucleomethylation of alkynes is developed, affording 3-methylindoles, 3-methylbenzofurans and 4-methylisoquinolines in moderate to excellent yields.     

Photochemical synthesis of heteroatom-containing polycyclic aromatic compounds

Anthra[2,1-b]furan, anthra[2,1-b]benzo[d]furan, anthra[2,1-b]thiophene, anthra[1,2-b]thiophene, anthra[2,1-b]benzo[d]thiophene, anthra[2,1-b]pyrrole and naphtho[2,3-c]carbazole derivatives were synthesized in fairly good yields by a one-pot photocycloaddition reaction of 2,3-disubstituted 1,4-naphthoquinone with 1,1-diarylethylene. This is the first reported synthesis of these aromatic compounds.     

A cascade process toward the synthesis of fused polycyclic dihydropyridines

The synthesis of fused polycyclic dihydropyridines was achieved using a cascade process comprising a Suzuki coupling, a nucleophilic cyclization and a hydrogen migration. Several functional groups are tolerated in this reaction and the methodology could be applied with success to quinoline and isoquinoline derivatives.     

Synthesis of functionalized polycyclic compounds via a novel aromatic oxy-Cope rearrangement

Polycyclic compounds have been prepared by aromatic dianionic oxy-Cope rearrangements involving the π bonds of two phenyl rings in a [3,3] sigmatropic rearrangement.     

Chemoselective intramolecular alkylation of the Blaise reaction intermediates: tandem one-pot synthesis of exo-cyclic enaminoesters and their applications toward the synthesis of N-heterocyclic compounds

The intramolecular alkylative reactivity and N/C selectivity of the various Blaise reaction intermediates, which are formed from the reaction of the Reformatsky reagents with ω-chloroalkyl nitriles, did not reach the synthetic potential as an entry to exo-cyclic enaminoesters. To circumvent this issue, various additives were investigated, among which the addition of NaHMDS dramatically enhanced the reactivity and N/C selectivity. This modification provided a highly efficient route for the synthesis of various N-fused heterocyclic compounds, as it requires only two steps from nitriles.     

Chromium-mediated synthesis of polycyclic aromatic compounds from halobiaryls

[reaction: see text] Reaction of 2,2'-dihalobiphenyl with butyllithium followed by the addition of chromium(III) chloride and alkynes afforded the corresponding phenanthrene derivatives via formal [4 + 2] cycloaddition. A variety of alkynes could be used for this reaction, such as alkyl, aryl, silyl, and alkoxycarbonyl alkynes. Repetitive process of the reaction gave more extended polycyclic compounds such as benzo[g]chrysene and azacyclopentaphenalene derivatives.     

Acid-promoted rearrangement of carbonate functionality anchored to the lower rim of a Calix

A unique calix[4]arene lower-rim intramolecular rearrangement, resulting in molecular asymmetry arising from the upper- and lower-rim substitution pattern, produces a new class of inherently chiral calix[4]arenes in a partial cone conformation. This was aided by molecular rigidification arising from pi-pi and C-H.pi interactions between bulky lower-rim substituents, with the corresponding circular dichroism spectra exhibiting the most intense bisignate Cotton effects yet observed for calix[4]arenes not bearing a chiral center.     

Triflic acid promoted synthesis of polycyclic aromatic compounds

The triflic acid (CF₃SO₃H) promoted cyclizations of 2-styrylbiaryls are found to be useful for the synthesis of polycyclic aromatic compounds, including functionalized derivatives of polycyclic aromatic compounds and heterocyclic systems. The reaction involves cationic cyclization followed by an elimination of benzene from the intermediate product.     

Tandem cobalt mediated rearrangement and Pauson-Khand reaction for the synthesis of functionalized polycyclic systems

The cobalt mediated rearrangement of enol ether complex 2 furnishes cyclic ketone 6, which undergoes an intramolecular Pauson-Khand reaction allowing access to functionalized polycyclic systems.     

Acid-promoted DNA-cleaving activities and total synthesis of varacin C

The first total synthesis of the antibiotic varacin C has been accomplished. In addition, it has been demonstrated that this antibiotic exhibits potent antitumor activity and is capable of causing efficient DNA cleavage under acidic conditions.     

Base- and ligand-free room-temperature synthesis of N-fused heteroaromatic compounds via the transition metal-catalyzed cycloisomerization protocol

A new practical method for the synthesis of N-fused heterocycles via the transition metal-catalyzed cycloisomerization of heterocyles possessing a propagyl group has been developed. This very mild, base- and ligand-free method allows for the synthesis of diverse fused heterocyclic cores in good to excellent yields.     

Orthogonal synthesis of pyrroles and 1,2,3-triazoles from vinyl azides and 1,3-dicarbonyl compounds

Tri- and tetrasubstituted N-H pyrroles were prepared by the simple treatment of vinyl azides with 1,3-dicarbonyl compounds in toluene at 100 °C via 2H-azirine intermediates generated in situ. When the reactions of vinyl azides and 1,3-dicarbonyl compounds were performed in DMF in the presence of a catalytic amount of K₂CO₃, 1-vinyl-1,2,3-triazoles were obtained via 1,3-dipolar cycloaddition. These methodologies exploited orthogonal modes of chemical reactivity of vinyl azides, which could be achieved by slight modification of the reaction conditions.     

Generation and reaction of heteroaromatic zirconocene: synthetic application to polycyclic heterocycles

Heteroaromatic zirconocene intermediates were generated by the reaction of ‘Cp₂Zr’ with alkoxymethyl-(TMS-ethynyl)-indole, -benzofuran or -benzothiophene derivatives under mild conditions in moderate to good yields. Copper-catalyzed C-C bond formation of the zirconocene intermediate with allylic halides gave allylation products, which were transformed into heterocyclic dienes through enyne metathesis. Preliminary Diels-Alder reaction of the dienes with DMAD showed notable site selectivity.