Reissert compound chemistry. XXVI. The syntheses of bis-benzylisoquinolines

The condensation of the anion of isoquinoline Reissert compounds with diaryl ethers is reported. These condensation products are converted into analogues of bis-benzylisoquinoline alkaloids.     

Reissert compound studies. XLV. The phenanthridine reissert compound

A series of phenanthridine Reissert compounds and Reissert analogs have been prepared using the trimethylsilyl cyanide method. The reactions of the conjugate base and fluoroborate salt have been studied and found, generally, to be similar to those of the isoquinoline Reissert compounds.     

Chemical modification of polymers. VII. Condensation of polymeric aldehydes with the anion of an isoquinoline reissert compound

The anion of the isoquinoline Reissert compound, 2-benzoyl-1,2-dihydroisoquinaldonitrile, reacts with polymeric aldehydes in essentially complete conversion, leading to polymeric esters containing isoquinoline moieties. These can be completely hydrolyzed to the corresponding alcohols. The reactivity of the Reissert anion toward polymeric halides and aldehydes is rationalized on the basis of its moderate hardness.     

Reissert compound studies. LXIV. Reissert compound and other products from an isolated N-benzoylisoquinolinium triflate salt

In the presence of trimethylsilyl trifluoromethanesulfonate, a methylene chloride solution of isoquinoline and benzoyl chloride gave N-benzoylisoquinolinium triflate ( 3 ) and N-H-isoquinolinium triflate ( 4 ). Depending on the reaction conditions, reaction of 3 may occur on the isoquinoline ring yielding a Reissert compound and 1,2-dihydroisoquinoline species. Otherwise, reactions transpire on the carbonyl of 3 to give an amide, an ester, and an anhydride.     

Reissert compound studies. XXVII. The reaction of the anion with 4-piperidones

The anion of the isoquinoline Reissert compound has been found to react with 4-piperidones to give esters of tertiary alcohols.     

A novel approach to 4-benzylisoouinolines

The reaction of quinone methides with 3.4-dihydroisoquinoline or isoquinoline leads to benzylisoquinoline derivatives. NMR and ms investigations as well as chemical degradation prove that benzylation takes place at C-4 of the isoquinoline nucleus. Spectroscopic data are given for all new compounds.     

Regioselective hydroxylation of phenols by simultaneous photochemical generation of phenol cation-radical and hydroxyl radical

Substituted phenols having pendant isoquinoline N-oxide were synthesized and their photochemical and luminiscent properties studied. Photolysis in an acid medium was found to yield the related photohydroxylation products, in a regioselective process, in addition to the isoquinoline deoxygenated precursor. Photoinduced electron transfer from the donor phenols to the protonated form of the first excited singlet state (S₁) of the pendant isoquinoline N-oxide acting as acceptor leads to a red-shifted emissive charge transfer (CT) state that is in fact a radical/cation-radical pair. Homolysis of the N-OH bond restores the aromatic isoquinoline nucleus and produces a hydroxyl radical that can couple to the required ring carbon in the phenol cation-radical to give the photohydroxylation products in a regioselective process controlled by the spin density of the phenol cation-radical. These photohydroxylation processes efficiently compete with the reported tendency to deprotonation in phenol cation-radicals. The photohydroxylation process by itself, and its regioselectivity, exclude a proton-coupled electron transfer mechanism or a consecutive electron transfer/deprotonation reaction. By contrast, the phenol cation-radical exists long enough to undergo the hydroxyl radical coupling reaction that leads to the photohydroxylation products.     

Iodine-mediated electrophilic cyclization of 2-alkynyl-1-methylene azide aromatics leading to highly substituted isoquinolines and its application to the synthesis of norchelerythrine

The reaction of 2-alkynyl-1-methylene azide aromatics 1 with iodine and/or other iodium donors, such as the Barluenga reagent (Py2IBF4/HBF4) and NIS, gave highly substituted cyclization products, namely, the 1,3-disubstituted 4-iodoisoquinolines 2, in good to high yields. Not only simple 2-alkynyl benzyl azides 1a-j and their substituted analogues 1k-u and 6 but also heteroaromatic analogues, including pyridine 8, pyrroles 10a-c, furane 10d, and thiophenes 10e-g, gave the corresponding isoquinoline derivatives in excellent to allowable yields. Electron-donating and electron-accepting substituents on the aromatic ring were equally tolerated, and either acidic or basic (or even neutral) reaction conditions, depending on the reactivity of the substrate, could be applied to smoothly convert the azide starting materials into the desired isoquinoline products in moderate to good yields. Limits were found only in connection with the substituent at the alkyne terminus, where electron-neutral or electron-donating substituents are clearly favored. The iodine-mediated electrophilic cyclization of 1 most probably proceeds through the iodonium ion intermediate 4 followed by nucleophilic cyclization of the azide and subsequent elimination of N2. This new methodology was successfully applied to the short synthesis of norchelerythrine.     

Reissert compound studies. XXX. Synthesis and alkylation of some new reissert compounds

The synthesis of several new isoquinoline Reissert compounds is described. Alkylation reactions of the anions of these new Reissert compounds and a rearrangement reaction are reported.     

Short and Efficient Syntheses of Protoberberine Alkaloids using Palladium‐Catalyzed Enolate Arylation

A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladium‐catalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50 % is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine‐containing derivative synthesized here.     

Bis(1,3,4-thiadiazolo)-1,3,5-triazinium halides. 2. Intramolecular ring transformation and synthesis of novel highly substituted guanidines.

Bis(1,3,4-thiadiazolo)-1,3,5-triazinium halides 6 can be easily attacked by nucleophiles at either the C(3a) or the C(4a) position of the central six-membered (cationic) ring. Nucleophilic attack leads to at least two reaction channels, one of which has been previously detected (pathway a) and leads to novel aminals 19. In this paper we report on a second channel (pathway b). Attack of primary or secondary amines 8 at C(3a) or C(4a) in 6 (and their analogues 7) leads to the weakly stabilized intermediates 14. A cascade of several proton shifts, ring openings, rearrangements, and ring closure processes is initiated which finally leads via 17 and 18 to novel highly substituted guanidines 9, 10, 12, and 13. Pathway b seems to be the result of well-balanced negative-hyperconjugative effects in 14 and/or 17 which control the highly selective opening of a relatively stable central 1,3,5-triazinium ring to yield the crucial intermediate 18. Some representatives of the guanidines have been characterized by X-ray analyses. Since some of the guanidines contain one or two chirality centers, an effort was made to investigate the stereochemistry of these compounds.     

Reaction of 1,2,3,4-tetrahydro-isoquinoline enamines with quinones

The reaction of p-benzoquinone with enamino amides derived from 2,2-dimethyl-1,2,3,4-tetrahydrobenzo[f]isoquinoline proceeds through a Michael addition. The reaction of this quinone with the base of drotaverine leads to a derivative of indolo[2,1-a]isoquinoline. Fusion of isoquinoline enamines by the action of 2,3-dichloro-1,4-naphthoquinone leads to pentacyclic benzo[g]naphtho-[2,3-b]indolyzine-8,13-dione. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1565–1570, October, 2006.     

Use of dilithio-tosylmethyl isocyanide in the synthesis of oxazoles and imidazoles

Dilithio-tosylmethyl isocyanide ($\text{2}$) reacts with the carbonyl of unsaturated esters to form oxazoles, unlike tosylmethyl isocyano monoanion which gives pyrroles by reaction with the conjugated carbon-carbon double bonds. Reaction of $\text{2}$ with carbon-nitrogen multiple bonds leads to imidazoles, an example of which is the one-step synthesis of imidazo[5,1-a]isoquinoline from isoquinoline. From $\text{2}$ and pyridine-N-oxide or pyridazine-N-oxide unsaturated ring opened products are obtained.     

Samarium-promoted coupling of pyridine-based heteroaryl analogues of benzylic acetates with carbonyl compounds

2-Substituted pyridine, quinoline, isoquinoline, bipyridine, and 1,10-phenanthroline analogues of benzylic acetates undergo SmI(2)-promoted coupling with aldehydes and ketones to afford (2-hydroxyalkyl)heteroaromatics. [reaction: see text]     

A Novel Three Component Reaction: The Synthesis of Stable,Highly Functionalized 1,4-Diionic Nitrogen Betaines

The protonation of a highly reactive 1,4-dipole generated in the reaction between pyridine or isoquinoline and dialkyl acetylenedicarboxylates by the acidic C-H group of (ethoxycarbonylmethyl) triphenylphosphonium bromide leads to a vinyl pyridinium cation derivatives, which undergo a carbon-centered Michael type addition with the conjugate base of the CH-acid to produce highly functionalized stable 1,4-diionic nitrogen betaines.     

A synthesis of dihydroimidazo[5,1-a]isoquinolines using a sequential Ugi-Bischler-Napieralski reaction sequence

A flexible route to analogues of dihydroimidazo[5,1-a]isoquinolines is described. The synthesis hinges on a sequential Ugi coupling, followed by a Bischler-Napieralski reaction to form the imidazole isoquinoline core. This route facilitates the introduction of a range of substitutions throughout the carbon framework.     

An effective BINAP and microwave accelerated palladium-catalyzed amination of 1-chloroisoquinolines in the synthesis of new 1,3-disubstituted isoquinolines

A facile and microwave accelerated reaction of 1-chloro-3-(4-chlorophenyl)isoquinoline with various heterocyclic amines, catalyzed by Pd, in the presence of BINAP additive and sodium carbonate as the base, leads to the formation of 3-(4-chlorophenyl)-1-(1H-1,2,3-triazol-1-yl)isoquinoline, 3-(4-chlorophenyl)-1-(1H-imidazol-1-yl)isoquinoline and 3-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)isoquinoline via Buchwald protocol in good yields. Similarly pyrazolylisoquinolines are also reported.     

Enamines of the 1,2,3,4-tetrahydroiso-quinoline series in the Chichibabin synthesis of pyrrolo[2,1-a]isoquinolines and in reaction with oxalyl chloride

It has been shown that the Chichibabin reaction of enamines of the 1,2,3,4-tetrahydroisoquinoline series and 1,2,3,4-tetrahydrobenzo[f]isoquinoline series with p-bromophenacyl bromide leads to pyrrolo[2,1-a]isoquinoline derivatives. The same heterocyclic system is obtained on interaction of 1-alkyl-3,4-dihydroisoquinolines or their benzo[f]-analogs with oxalyl chloride. The obtained dioxopyrrolines form derivatives of benzo[g]quinoxalino[2,3-b]indolizine on condensation with o-phenylenediamine. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1068–1074, July, 2007.     

The NMR spectra of the porphyrins. 17—Metalloporphyrins as diamagnetic shift reagents,structural and specificity studies

The nature of the metalloporphyrin-ligand complexes produced by zinc, magnesium and cobalt porphyrins with basic ligands has been investigated using the diamagnetic ring current shifts of the porphyrin on the ligand protons. The metal to nitrogen bond lengths in some metallo-meso-tetraphenylporphyrin (pyridine) complexes have been determined and compared with the data of the crystalline complexes. The geometry of the Zn meso-tetraphenylporphyrin complexes with 2-picoline, quinoline and isoquinoline has been investigated. Steric interactions between the ligand and the porphyrin in 2-picoline and quinoline produce a dramatic increase in the Zn? N bond length when compared to the unstrained analogues pyridine and isoquinoline. This large increase is associated with comparatively minor angle distortions in the complex. The specificity of the Zn meso-tetraphenylporphyrin complexation shifts has been determined for a range of benzyl and butyl compounds. The complexation shift is linearly related to the basicity of the ligand for a wide range of basicities.     

Supplementary Observations on the Chemistry of the Alkaloids of Berberine Series. II. The Ultraviolet Absorption Spectra of Berberines and Related Compounds

The ultraviolet absorption spectra of berbines and ?-berbines consist of a single, weak and narrow band in which λ_max position dependeds on the kind of auxochrome group i. e., methylenedioxy-or dimethoxy group attached to 2–3 position. The effect of the auxochrome group at 11–12 position or 12–13 position is very small. The shape of the band of oxyberberine, oxy-?-berberine and oxyprotoberberine are similar, especially those of the latter two substances resemble closely. Comparing with isoquinoline, the bands (b), (c) and (d) of G-berberines and protoberberine are considered as characteristic of isoquinoline structure, while the band (a) in visible region is of berberinium structure, however, the absorption curve of ?-berberines does not show any characteristic of isoquinoline or berberinium structure.