Tetralones as precursors for the synthesis of 2,2′-disubstituted 1,1′-binaphthyls and related compounds

Using tetralones as starting materials, the synthesis of biaryl compounds is described in this paper. The tetralones were initially converted into 1-bromo-3,4-dihydro-2-naphthalenecarbaldehydes before effecting aromatization into the corresponding naphthalenes. These products were then subjected to Suzuki-Miyaura cross-coupling reactions, with a variety of aromatic boronic acids containing substituents in the ortho position, to afford biaryl compounds. The biaryl compounds possess heteroatom containing substituents ortho to the newly formed biaryl axis.     

Lewis acid-catalysed one pot synthesis of substituted xanthenes

A direct synthesis of substituted xanthenes from salicylaldehydes and cyclohexenones or tetralones has been developed. The reaction is catalysed by Lewis acids like scandium triflate and furnishes substituted xanthenes in good to excellent yields using either microwave or thermal heating. Microwave heating results in significantly shortened reaction times of 30 min and generally higher yields.     

Regioselective Arene Functionalization: Simple Substitution of Carboxylate by Alkyl Groups

Arenes with various alkyl side‐chains were synthesized in high yields and excellent regioselectivities. Starting from toluic and naphthoic acids, the carboxylate group was conveniently substituted by alkyl halides by Birch reduction and subsequent decarbonylation. The method is characterized by inexpensive starting materials and reagents, and methylation of arenes was realized. Besides simple alkyl substituents, the scope of arene functionalization was extended by benzyl, fluoro, amino, and ester groups. We were able to control the alkylation of 1‐naphthoic acid during Birch reduction by the addition of tert‐butanol. This allowed the regioselective synthesis of mono and bis‐substituted naphthalenes from the same starting material.     

Synthesis of o-nitrosoacylbenzenes from o-nitrobenzyl alcohols and their derivatives

Nitration of substituted benzyl alcohols, as well as ethers and esters derived therefrom, with nitric acid in acetic anhydride was studied. The corresponding o-nitrobenzyl alcohols and their derivatives formed as the primary products are capable of being converted into o-nitrosoacylbenzenes by the action of acids.     

New synthesis of substituted 3-aryl-1-naphthaldehydes

A general, unequivocal procedure for the preparation of specifically substituted 3-aryl-1-naphthaldehydes was developed. Benzylmagnesium bromides with 5-aryl-2, 2-dimethyl-4-pentene-3-ones (12) gave exclusively 1,4-addition products, 5,6-diaryl-2,2-dimethyl-3-hexanones (13). The hexanones on oxidation with peracetic acid gave 3,4-diarylbutanoic acids (14), which were cyclized to tetralones (15). The tetralones on treatment with MeMgI followed by dehydration and dehydrogenation gave 3-aryl-1-methylnaphthalenes (10), which were converted into corresponding aldehydes (11). When benzylmagnesium bromides were added to 4-aryl-3-butene-2-ones (1), mixtures of 1,2 and 1,4-addition products were formed. Further treatment of these mixtures also yielded the desired methylnaphthalenes along with various identified side products.     

Synthesis of the bis-potassium salts of 5-hydroxy-3-oxopent-4-enoic acids and their use for the efficient preparation of 4-hydroxy-2H-pyran-2-ones and other heterocycles

5-Hydroxy-3-oxopent-4-enoic acid esters can be efficiently transformed into the stable bis-potassium salts of the corresponding 5-hydroxy-3-oxopent-4-enoic acids, from which the sensitive acids are released in situ, the latter being converted into substituted 4-hydroxy-2H-pyran-2-ones, pyrazoles and isoxazoles under mild conditions; the efficiency of this method is demonstrated by the first synthesis of two naturally occurring pyrones.     

Carbopalladation of nitriles: synthesis of benzocyclic ketones and cyclopentenones via Pd-catalyzed cyclization of omega-(2-iodoaryl)alkanenitriles and related compounds

An efficient procedure for the synthesis of 2,2-disubstituted benzocyclic ketones by intramolecular carbopalladation of nitriles has been developed. The cyclization of substituted 3-(2-iodoaryl)propanenitriles affords indanones in high yields. The reaction is compatible with a wide variety of functional groups. This methodology has been extended to the synthesis of tetralones and cyclopentenones.     

Synthesis of substituted naphthalenes and carbazoles by the palladium-catalyzed annulation of internal alkynes

An efficient synthesis of highly substituted naphthalenes has been developed by the palladium-catalyzed annulation of a variety of internal alkynes, in which two new carbon-carbon bonds are formed in a single step under relatively mild reaction conditions. This method has also been used to synthesize carbazoles, although a higher reaction temperature is necessary. The process involves arylpalladation of the alkyne, followed by intramolecular Heck olefination and double-bond isomerization. This method accommodates a variety of functional groups and affords the anticipated highly substituted naphthalenes and carbazoles in good to excellent yields.     

The synthesis of diastereo- and enantiomerically pure beta-aminocyclopropanecarboxylic acids

The synthesis of diastereo- and enantiomerically pure beta-aminocyclopropanecarboxylic acids (beta-ACCs) is described. Starting from pyrrole, (rac)-4 is readily obtained, which was kinetically resolved by enzymatic hydrolysis. Subsequent oxidation of (-)-4 and deformylation gives rise to the cis-beta-ACC derivative (ent)-9, while (+)-10 was converted to the trans-beta-ACC derivative 8. Both 8 and (ent)-9 and their benzyl esters 13 and 16, being conformationally restricted beta-alanine or gamma-aminobutyric acid (GABA) derivatives, represent useful building blocks for peptides containing unnatural amino acids.     

Bifunctional Brønsted Base Catalyst Enables Regio‐, Diastereo‐, and Enantioselective Cα‐Alkylation of β‐Tetralones and Related Aromatic‐Ring‐Fused Cycloalkanones

The catalytic asymmetric synthesis of both α‐substituted and α,α‐disubstituted (quaternary) β‐tetralones through direct α‐functionalization of the corresponding β‐tetralone precursor remains elusive. A designed Brønsted base‐squaramide bifunctional catalyst promotes the conjugate addition of either unsubstituted or α‐monosubstituted β‐tetralones to nitroalkenes. Under these reaction conditions, not only enolization, and thus functionalization, occurs at the α‐carbon atom of the β‐tetralone exclusively, but adducts including all‐carbon quaternary centers are also formed in highly diastereo‐ and enantioselective manner.     

Preparation of phenyl-butyraldehydes using a base-catalyzed aromatization of dienones

Seven aldehydes were prepared using a five-step sequence synthesis. The synthetic strategy involved the use of a novel aromatization reaction of dienones. These key intermediates were prepared following a sequence involving BAR of substituted tetralones, ketones reduction, protection of alcohol, and bis-allylic oxidation. The key step of the route is an aromatization promoted by basic reaction conditions of dienones leading to substituted 4-phenyl butanals.     

An alkaloid-mediated desymmetrization of meso-anhydrides via a nucleophilic ring opening with benzyl alcohol and its application in the synthesis of highly enantiomerically enriched β-amino acids

The cinchona alkaloid-mediated opening of prochiral cyclic anhydrides in the presence of benzyl alcohol leading to optically active hemiesters is described. Structurally diverse anhydrides are converted into their corresponding benzyl monoesters with either enantiomer being obtained with up to 99% e.e. by using quinine or quinidine as the directing additive. A simple aqueous work-up protocol permits the isolation of the products in analytically pure form and the recovery of the alkaloids almost quantitatively. These hemiesters can be converted to N-protected β-amino esters by means of Curtius degradation of the corresponding acyl azides. Subsequent cleavage of both protecting groups by a single reaction step leads to the free β-amino acids in excellent yields. The efficiency of this procedure is demonstrated by the short asymmetric synthesis of the fungicide cis-pentacin delivering the amino acid with >99.7% enantiomeric excess.     

Eine neue Synthese von methoxylierten meso-Benzanthronen; Abbau zu 5,8-Dihydroxy-anthrachinon-1-carbonsäure und 5,7,8-Trihydroxy-anthrachinon-1-carbonsäure

Methyl benzoquinone carboxylate and its 5-methoxy- and 6-methoxy-derivatives condense smoothly with β-methoxynaphthalene in an acid catalysed reaction to give α-arylsubstituted naphthalenes 7 , which, after reduction, methylation and intramolecular acylation yield tri-and tetramethoxylated 7 H-Benz[d, e]anthracene-7-ones 9 . Partial degradation by means of chromic acid or permanganate leads to a regiospecific synthesis of a substituted phenalenone ( 10 ) and/or methoxy-anthraquinone-1-carboxylic acids. Phthalid anion has been added on to methyl methoxy benzoquinone carboxylate to yield the adducts 4 .     

Synthesis of 5H-tetrazolo[5,1-c][1,4]benzodiazepines

A three step synthesis of 5H-tetrazolo[5,1-c][1,4]benzodiazepin-11-ones 8a-d via the reaction of a substituted benzyl azide and ethyl cyanoformate is described. The derived lactams are converted to the corresponding 11-thiones 9a-d and, through the S-methylated derivatives, to the 11-amino analogs 11a-f. All of the described compounds are representatives of a novel ring system.     

Preparation and structure of novel hexaazaisowurtzitane cages

Hexaazaisowurtzitane or cage molecules have attracted attention concerning their synthesis because hexanitrohexaazaisowurtzitane (HNIW or CL20) is presently the most powerful energetic compound. The synthesis of hexaazaisowurtzitanes was considered to be limited solely to the condensation of certain benzylamines with glyoxal. Here, we present the synthesis and characterization of seven novel non-benzylic hexaazaisowurtzitanes, such as hexapropargylhexaazaisowurtzitane. The substituents on the six nitrogen atoms are different to those of the benzyl or substituted benzyl groups to which previous syntheses were limited. X-ray structures are given for the hexapropargyl and hexa-2-thienylmethylene derivatives. Steric strains limit the synthesis with alpha-substituted benzyl and allyl derivatives. The reaction mechanism and the role of the intermediate diimines are discussed. Some of the novel hexaazaisowurtzitanes are potential precursors of hexanitrohexaazaisowurtzitane.     

Porphyrins with exocyclic rings. Part 21: Influence of pyrrolic and carbocyclic ring alkyl substituents on the synthesis of porphyrins bearing six-membered exocyclic rings

A series of 5-substituted 4,5,6,7-tetrahydroindoles were prepared by reacting 4-substituted cyclohexanones with phenylhydrazones derived from esters of acetoacetic acid under Knorr-type reaction conditions. Related 6,6-dimethyltetrahydroindoles were also prepared by reacting dimedone with oximes by the Knorr pyrrole syntheses, followed by selective reduction of the remaining ketone moiety with diborane. The substituted tetrahydroindoles were regioselectively oxidized with lead tetraacetate to give the related 7-acetoxy derivatives, and these reacted with 5-unsubstituted pyrrole esters to give pyrrolyltetrahydroindoles. In one case, a bromo substituent was used to protect the β-position of the pyrrole reactant. Cleavage of the benzyl ester protective groups with hydrogen over Pd/C, which also removes the bromo-protective group, gave four dipyrrole carboxylic acids. These were condensed with a dipyrrylmethane dialdehyde using the MacDonald ‘2+2’ condensation to give substituted porphyrins with six-membered exocyclic rings. These structures are useful for comparison to porphyrin samples found in organic-rich sediments such as oil shales and petroleum. The presence of methyl substituents on the six-membered ring for the tetrahydroindole precursors slightly decreases the yields for porphyrin synthesis, and this effect is enhanced when the system becomes more sterically crowded due to the presence of an ethyl group of the adjacent pyrrole ring. 5-Alkyl substituted tetrahydroindoles were also converted to tetrapropanoporphyrins via a cyclotetramerization procedure. The alkyl substituents again decreased the yields, although 5-alkyl substituents were found to have a far less deleterious effect than 6-alkyl groups. In addition to providing samples to help assign the vibrational spectra of geoporphyrin samples, these results demonstrate that highly substituted porphyrin systems can be prepared from tetrahydroindole derivatives.     

Highly regioselective synthesis of 1,3-diiodonaphthalene derivatives via a sequential cascade iodocyclization

A novel and flexible sequentially cascade iodocyclization for the synthesis of highly substituted 1,3-diiodinated naphthalene derivatives in up to 99% yield under mild conditions is reported. The dihalogenated moiety can be readily introduced into the naphthalenes in a position that is usually not easily functionalized.     

Naphthalenes,isoquinolines, and a benzazocine from zirconocene-copper-mediated coupling of benzocyclobutadiene with nitriles and alkynes

[reaction: see text] Commercially available 1-bromobenzocyclobutene is a potentially useful synthon particularly with the application of organometallic methodology. Here we show that it is readily converted into Cp(2)Zr(benzocyclobutadiene), which couples with alkynes or nitriles giving five-membered zirconacycles. Treatment of these alkyne- or nitrile-derived zirconacycles with CuCl yields substituted naphthalenes, isoquinolines, or in the presence of MeO(2)C-CC-CO(2)Me, a 3-benzazocine containing an eight-membered ring [corrected].     

Intermolecular Dearomatization of Naphthalene Derivatives by Photoredox‐Catalyzed 1,2‐Hydroalkylation

An intermolecular hydroalkylative dearomatization of naphthalenes with commercially available α‐amino acids is achieved via visible‐light photoredox catalysis. With an organic photocatalyst, a series of multi‐substituted 1,2‐dihydronaphthalenes are obtained in good‐to‐excellent yields. Intriguingly, by tuning the substituents at the C2 position of naphthalenes, formal dearomative [3+2] cycloadditions occur exclusively via a hydroalkylative dearomatization–cyclization sequence. This overall redox‐neutral method features mild reaction conditions, good tolerance of functionalities, and operational simplicity. Diverse downstream elaborations of the products are demonstrated. Preliminary mechanistic studies suggest the involvement of a radical–radical coupling pathway.     

Synthesis of substituted naphthalenes from alpha-tetralones generated by a xanthate radical addition-cyclisation sequence

A simple, highly efficient and cheap synthesis of substituted naphthalenes is reported. These aromatic compounds can be easily prepared in acidic or basic conditions from [small alpha]-tetralones, obtained by a xanthate-mediated addition-cyclisation sequence.