One-pot N-dealkylation and acid-catalyzed rearrangement of morphinans into aporphines

The one-pot N-demethylation and acid-catalyzed rearrangement of morphinan-N-oxides offers a new, shorter and more efficient route to neuropharmacologically important N-substituted aporphines. An improved procedure is described for the preparation of the starting alkaloid N-oxides using Na₂WO₄ as catalyst. The transetherification during the rearrangement of codeinone into 2-O-alkyl-norapocodeines is documented.     

Benzylation of morphinandienes and new aspects of their acid-catalyzed rearrangement to new aporphines

The benzylation of thebaine and 6-demethoxythebaine resulted in different product mixtures. Explanations were given for both the observed differences in the ratio of 5β- versus 7-benzyl products and the deviation of the electronic structure of ring C of 7-benzyl products. The acid-catalyzed rearrangement of morphinan-5,8-dienes, 5,6- and 6,7-disubstituted morphinan-6,8-dienes was achieved and mechanistic interpretations for the formation of new, potentially dopamine-active aporphines were provided.     

Synthesis of 1,4-diazepin-5-ones under microwave irradiation and their reduction products

A new efficient access to 1,4-diazepane derivatives is described via a microwave assisted synthesis of 7-substituted-1,4-diazepin-5-ones, which proceeds rapidly in good yields. Catalytic reduction gave 1,4-diazepan-5-ones and 1,4-diazepanes whereas a ring opening was observed by hydride reduction when a phenyl group occupies the N-benzylic position.     

Studies on the deprotonation and subsequent [1,4]-Wittig rearrangement of α-benzyloxyallylsilanes

Upon exposure to s-BuLi, benzyloxyallylsilane undergoes an unusually rapid and efficient [1,4]-Wittig rearrangement. Herein we describe efforts aimed at trapping the intermediate α-carbanion with an electrophile prior to rearrangement. The results of these experiments indicate that α-deprotonation and bond reorganization are separate events. Findings herein further indicate that the future success of benzyloxyallylsilanes in [1,4]-Wittig rearrangements will likely hinge on the acidity of the benzylic protons.     

Synthesis of 3-alkyl-1,4-dihydrocyclopenta[b]indoles: unexpected formation of dimeric compounds

Acid-catalyzed dehydration of 3-alkyl(aryl)-4-methyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-ols gives dimeric derivatives of 3-alkyl(aryl)-4-methyl-1,4-dihydrocyclopenta[b]indole.     

n-Butyltriphenylphosphonium peroxodisulfate: A cheap and efficient reagent for the aromatization of Hantzsch 1,4-dihydropyridines

Different 4-substituted 1,4-dihydropyridines have been oxidized to pyridine derivatives by n-butyltriphenyl phosphonium peroxodisulfate in acetonitrile solution at reflux condition.Formation of two kinds of products has been observed depending on the type of 4-substituent.     

Synthesis and structure elucidation of oxidative coupling products of 2-hydroxy-1,4-naphthoquinones

2,3-Dihydro-3-O-(1,4-naphthoquinon-2-yl)-2-oxo-1,4-naphthoquinones are the products of oxidative coupling of substituted 2-hydroxy-1,4-naphthoquinones (regardless of the presence of peri-hydroxy groups in their structures) under the action of lead dioxide. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 294—298, February, 2006.     

Synthesis of functionalized cage propellanes and D3-Trishomocubanes via the ring-closing metathesis and acid-promoted rearrangement

Several functionalized cage propellanes and D₃-trishomocubanes containing spiro linkage have been reported starting with commercially available materials such as 1,4-hydroquinone and dicyclopentadiene. In this regard, Claisen rearrangement, Diels–Alder reaction (DA), ring-closing metathesis (RCM) and acid-promoted rearrangement have been used as key steps. The strategies described here, opens up new opportunities to assemble intricate cage systems that are difficult to construct by conventional methods. Carbocation intermediates generated during the rearrangement process play a prominent role in designing unusual cage systems. One of the rearranged cage compound's structure was unambiguously established by single crystal X-ray diffraction studies.     

Methods for the Synthesis of Heteroaryl-substituted 1,4-Benzo- and 1,4-Naphthoquinones. (Review)

Methods for the synthesis of heteroaryl-substituted 1,4-benzo- and 1,4-naphthoquinones with a C-C bond between the heterocycle and quinone fragments are reviewed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 803–833, June, 2005.     

Different rearrangement behaviour of the cation or anion derived from the Diels-Alder adduct of 9-ferrocenylanthracene and 1,4-benzoquinone: ring-opening or paddlewheel formation

Prototropic rearrangement of the Diels-Alder adduct (3a) of 9-ferrocenylanthracene and 1,4-benzoquinone potentially furnishes 9-ferrocenyl-1,4-dihydroxytriptycene (3b) incorporating a C(2v) symmetrical paddlewheel moiety. However, reaction of 3a with HBF(4) unexpectedly yields instead 9-ferrocenyl-10-(2,5-dihydroxyphenyl)anthracene (4) via cleavage of the C9-C12 bond to generate initially a ferrocenyl-stabilized cation. Treatment of 3a with sodium hydride and iodomethane yields 1,4-dimethoxy-9-ferrocenyltriptycene (3c) in high yield but, surprisingly, also leads to fission of the C9-C12 bond resulting, after methylation, in the formation of 9-hydroxy-9-ferrocenyl-10-(2-hydroxy-5-methoxyphenyl)dihydroanthracene (12), which readily dehydrates on silica to form 9-ferrocenyl-10-(2-hydroxy-5-methoxyphenyl)anthracene (8). The X-ray crystal structures of 3a, 3c and 4 are reported.     

Synthesis and study of novel fulleropyrrolidines bearing biologically active 1,4-dihydropyridines

New fulleropyrrolidines endowed with chlorine-containing biological active 1,4-dihydropyridines (1,4-DHPs) have been synthesised from the respective formyl substituted 1,4-DHPs by following Prato's procedure. The presence of the chlorine atom on C2 of the 1,4-DHP ring brings about important spectroscopical and structural differences in compounds 10a-f related to the parent hydrogen-containing 11a. The mass spectroscopy study reveals different fragmentation patterns for fulleropyrrolidines 10a-f and their precursors 1,4-DHPs, as well as with 11a. Semiempirical calculations (AM1 and PM3) predict a most stable stereoisomer in all cases (RS for 10a-f) and the same RR for 11a. The presence of chlorine atom in 10a-f is responsible for the higher calculated conformational energy barriers in comparison with 11a. The geometry of the 1,4-DHP shows that the presence of fullerene unit does not significantly alter the required conformation for biological activity.     

Phosphorus-containing disiloxanes: Synthesis and thermal rearrangement of the 1,2-shift type

Methods for the synthesis of tetramethylbis(ω-phosphoryloxyalkyl)disiloxanes were developed. Thermal rearrangement of the 1,2-shift type of tetramethylbis(phosphoryloxymethyl)disiloxanes was studied. The 1,2-shift rearrangement of dimethyl(diphenoxyphosphoryloxymethyl)silyl hydrogen sulfate was found. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1210–1214, May, 2005.     

Selective oxidation of acetylenic 1,4-diols with dioxiranes in comparison with the methyltrioxorhenium-hydrogen peroxide oxidant

Dimethyldioxirane (1a) and its trifluoro analog (1b) were employed to achieve selectively the direct transformation of hex-3-yne-2,5-diol 3a and 1,4-diphenyl-but-2yne-1,4-diol 3b (two representative acetylenic 1,4-diols) into the corresponding carbonyls, leaving the carbon-carbon triple bond moiety untouched. The results are compared with those recorded in the analogous oxidation using the methyltrioxorhenium (MTO)/85% H₂O₂ homogeneous system. The powerful methyl(trifluoromethyl)dioxirane (1b) is the reagent of choice to achieve optimum yields of the target alkyne-1,4-diones, which are extremely versatile synthons.     

Synthesis of macrocyclic 1,1′-biarenol derivatives by the tandem Claisen rearrangement and their binding properties

Crown ether-type macrocycles consisting of an enantiopure biarenol derivative and an oligoethylene glycol were synthesized by the Lewis acid-mediated tandem Claisen rearrangement. This is the first example of the successful application of the tandem Claisen rearrangement to the synthesis of enantiopure macrocyclic biarenol derivatives. The enantiopure macrocyclic biarenols were found to form 1:1 complexes with amino acid salts and to discriminate their chirality.     

Aromatization of Various 1,4‐Dihydropyridines by Tetrabutylphosphonium Dichromate (TBPDC) under Conventional Heating and Microwave Irradiation

Tetrabutylphosphonium dichromate (TBPDC) has been found an efficient oxidizing agent for the aromatization of various 1,4‐dihydropyridines to their pyridine derivatives in refluxing acetonitrile and also under microwave irradiation. Short reaction times and clean workup are the advantages of this method.     

Convenient Synthesis of 2-Allyl-3-bromo-1,4-dimethoxynaphthalene: Key Intermediate as Building Block for Bioactive Pyranonaphthoquinones

Synthesis of a key precursor 2-allyl-3-bromo-1,4-dimethoxynaphthalene (1) used in constructing various naturally occurring biologically active pyranonaphthoquinones is carried out utilizing easily available 1-methoxynaphthalene as a starting material. The synthesis was accomplished with Dakin's oxidation and Claisen rearrangement, thereby providing another easy approach toward (1) without involving highly lachrymatric 2-bromonaphthoquinone.     

α-Trifluoroacetyl-δ-valerolactone: synthesis, acyl-lactone rearrangement and unexpected easy decarboxylation of the rearranged product

Claisen condensation of δ-valerolactone and ethyl trifluoroacetate leads to α-trifluoroacetyl-δ-valerolactone, existing completely in CDCl₃ solution as an enol. Upon treatment of this cyclic 1,3-ketoester with aqueous HCl, an acyl-lactone rearrangement takes place. The structure of the resulting pyran was confirmed by an X-ray analysis. The ability of the rearrangement product to lose its carboxylic group under unexpected mild conditions was used for the synthesis of the corresponding 3-unsubstituted cyclic hemi-ketal.     

Unusual rearrangement of spiro β-lactams to 1,4-diazabicyclo[4,4,0]decanes and 1,4-diazabicyclo[4,3,0]nonanes. Synthesis of conformationally restricted σ-receptor ligands

Synthesis of 1,4-diazabicyclo[4,4,0]decanes and 1,4-diazabicyclo[4,3,0]nonanes was achieved by using 4-formyl spiro β-lactams as easily available starting materials. Furthermore, the application of this protocol to the preparation of conformationally restricted σ-receptor ligands was also performed. Theoretical calculations were carried out on a model reaction, in order to give some understanding of the reaction mechanism.     

Microwave-assisted combined Mitsunobu reaction-Claisen rearrangement and microwave-assisted phenol oxidation: rapid synthesis of 2,6-disubstituted-1,4-benzoquinone natural products

Microwave irradiation of a phenol, an allylic alcohol, di-isopropyl azodicarboxylate and triphenylphosphine at 220-240 °C for 30 min results in a combined Mitsunobu reaction and Claisen rearrangement to give the rearranged 2-allylphenol. Following the first detailed study of microwave-assisted phenol oxidation, rapid syntheses of the natural products primin and 2-methoxy-6-pentadecyl-1,4-benzoquinone (four reaction steps, total reaction time 1 h) were achieved using this combined Mitsunobu-Claisen strategy in combination with two further microwave-assisted steps (alkene hydrogenation and phenol oxidation).     

Synthesis of new linear polymers containing phosphorus atom in the main chain by the radical polyaddition: Addition polymers of phenylphosphine with 1,4-divinylbenzene or 1,4-diisopropenylbenzene and their properties

A polyaddition of phenylphosphine (PH) to 1,4-divinylbenzene (DVB) or 1,4-diisopropenylbenzene (DIPB) was carried out by radical initiations or UV irradiation at 60–80°C in toluene under a nitrogen atmosphere. The soluble polymer with higher molecular weight () was obtained in a high yield with AIBN initiator for 95 h in the presence of 5% excess of PH to DVB (monomer feed ratio [DVB]₀/[PH]₀ = 1/1.05). On the other hand, a polyaddition of PH to DIPB proceeded much slower than the case of DVB, but the high polymer was obtained in a high yield by choosing polyaddition conditions such as polyaddition temperature and initiator concentration. From ¹H-NMR, IR analyses, and phosphorus content of the polymers, it was characterized that both polymers have the alternating structure consisting of PH and DVB or DIPB units in 1 : 1 ratio. The glass transition and decomposition temperatures of both polymers under a nitrogen atmosphere were almost similar: 15–30°C and 380–385°C, respectively; but, the polymers were oxidized by heating under an atmosphere of air. The polymers had a self-extinguishing property and the polymer blend of the flammable polymers such as polystyrene and polyethylene with the phosphorus-containing polymers exhibited an excellent flame resistance. © 1994 John Wiley & Sons, Inc.