Nitroimidazoles X . Syntheses of substituted 2-(1-methyl-5-nitro-2-imidazolyl)quinolines

Reduction of substituted-2-nitrobenzaldehyde (1) afforded substituted-2-aminobenzaldehyde (2) . Reaction of compound 2 with 2-acetyl-1-methyl-5-nitroimidazole (3) under basic conditions afforded substituted 2-(1-methyl-5-nitro-2-imidazolyl)quinolines 4 . Reaction of compound 4 (R = X) with hydrogen peroxide in acetic acid afforded compound 5 which was transformed to compound 6 with phosphorus oxychloride.     

Synthesis of N‐benzoylamino‐1,2,3,6‐tetrahydropyridine derivatives as potential anti‐inflammatory agents

N‐Benzoylamino‐1,2,3,6‐tetrahydropyridines 9a‐q were synthesized from 4‐substituted pyridines in four steps. Amination of pyridines was carried out to prepare intermediate N‐aminopyridinium mesylates using mesytelenesulfonyl hydroxmate (MSH) as aminating agent. N‐aminopyridinium mestylates reacted with appropriately substituted acyl chlorides to form N‐ylides as stable crystalline solids. Partial reduction of N‐ylides with mild reducing agent afforded N‐benzoylamino‐1,2,3,6‐tetrahydropyridines in fair to good yields.     

Stereoselective reduction of α-alkoxy acetylenic ketones with zinc borohydride and K-selectride.

Reduction of α-benzyloxy acetylenic ketones with zinc borohydride afforded the erythro-acetylenic vicinal diols in 95% stereoselectivity, while reduction with K-selectride gave the isomeric threo-diols in 90% stereoselectivity.     

Synthesis and structure of the dithienostannole anion

Novel dithienostannoles were synthesized by the reactions of the corresponding dilithiobithiophenes with dichlorodiphenylstannane. A unique byproduct, 10-membered ring compound was also obtained. Reduction of type A dithienostannole with lithium afforded 2,2′-dilithio-3,3′-bithiophene, while reduction of type B dithienostannole with lithium afforded the corresponding dithienostannole anion. The structure and aromaticity of the dithienostannole anion are also discussed.     

Synthesis and Aza-[2,3]-Wittig Rearrangements of Vinylaziridines: Scope and Limitations

cis- and trans-2,3-Trisubstituted vinylaziridines have been prepared from cis- and trans-epoxy alcohols, respectively, and used as substrates in the aza-[2,3]-Wittig rearrangement. Five different anion-stabilizing groups have been investigated for their efficiency to promote the rearrangement, and it was found that N-tert-butyl acetyl vinylaziridines were superior in this reaction, affording the corresponding cis-2,6-tetrahydropyridines (>90%) as single isomers when treated with LDA. Similarly, the corresponding (Z)-propenylaziridines gave trans,trans-2,3,6-trisubstituted tetrahydropyridines as the sole products while the (E)-propenylaziridines afforded the cis,cis-2,3,6-derivatives with equally high selectivity. The scope and limitations of the process have been investigated by varying the structure of the substrate, and the mechanism of the rearrangement has been probed to some extent; the mechanistic picture is more complex than assumed previously.     

A possible electron-ionization induced elimination of dioxetane from the deglycolization product of lithium aluminum hydride reduction of the ethylene acetal of methyl o-formylbenzoate

Reduction of the ethylene acetal of methyl o-formylbenzoate with lithium aluminum hydride afforded 1,2 bis(2-oxaindan-1-yloxy)ethane(V a), whose interesting mass spectroscopic behavior is discussed.     

Synthesis,reduction, and reductive alkylation of a few tricyclic α,β-unsaturated ketones

Reduction and reductive alkylation of the tricyclic α,β-unsaturated ketones 9–12 afforded the saturated ketones 13–21 in high yields.     

Phosphine‐Catalyzed [4+2] Cycloadditions of Allenic Ketones: Enantioselective Synthesis of Functionalized Tetrahydropyridines

Amino‐acid‐derived phosphine catalyzed [4+2] cycloaddition leading to chiral tetrahydropyridines, making use of α‐substituted allenic ketones as “C4 synthons” and N‐sulfonyl cyclic ketimines, has been developed. This asymmetric cycloaddition tolerates a wide range of α‐substituted allenic ketones. A series of chiral sultam‐fused tetrahydropyridines bearing a quaternary stereocenter were obtained in high yields with good enantioselectivities.     

Synthesis of tri-substituted biaryl based trianglimines: formation of C3-symmetrical and non-symmetrical regioisomers

2-Functionalised aromatic monoaldehydes were synthesised in good to excellent yields by reacting 4-bromo-2-fluorobenzaldehyde with different secondary amines and phenol. The Suzuki-coupling reaction of the newly functionalised aromatic monoaldehydes with 4-formylphenylboronic acid afforded the corresponding 2-functionalised-4,4'-biphenyldialdehydes in good yields (47-85%). The [3+3]-cyclocondensation reactions of the 2-functionalised-4,4'-biphenyldialdehydes with (1R,2R)-1,2-diaminocyclohexane afforded a mixture of regioisomeric C(3)-symmetrical and non-symmetrical trianglimines. Reduction of the C(3)-symmetrical and the non-symmetrical trianglimines with NaBH(4) in a mixture of THF and MeOH afforded the corresponding trianglamines in high yields.     

Organocatalytic Enantioselective Oxidative CH Alkenylation and Arylation of N‐Carbamoyl Tetrahydropyridines and Tetrahydro‐β‐carbolines

The first organocatalytic enantioselective C? H alkenylation and arylation reactions of N‐carbamoyl tetrahydropyridines and tetrahydro‐β‐carbolines (THCs) are described. The metal‐free processes represent an efficient and straightforward approach to a variety of structurally and electronically diverse α‐substituted tetrahydropyridines and THCs in good yields with excellent regio‐ and enantioselectivities. Preliminary control experiments provide important insights into the reaction mechanism.     

Tricyclic chemistry. Synthesis and chemistry of a novel polyheterocycle

The photochemical reaction of 1 with acrylonitrile gave the cyclobutane adducts II and III, which on treatment with base afforded a novel polycyclic structure IV. Reduction of IV with LAH followed by Eschweiler-Clarke methylation yielded the polyheterocyclic structure VI.     

Economical Access to Diverse Enantiopure Tetrahydropyridines and Piperidines Enabled by Catalytic Borrowing Hydrogen

We disclose herein a catalytic borrowing hydrogen method that enables an unprecedented, economical one-pot access to enantiopure tetrahydropyridines with minimal reagent use or waste formation. This method couples a few classes of readily available substrates with commercially available 1,3-amino alcohols, and delivers the valuable tetrahydropyridines of different substitution patterns free of N-protection. Such transformations are highly challenging to achieve, as multiple redox steps need to be realized in a cascade and numerous side reactions including a facile aromatization have to be overcome. Highly diastereoselective functionalizations of tetrahydropyridines also result in a general access to enantiopure di- and tri-substituted piperidines, which ranks the topmost frequent N-heterocycle in commercial drugs.     

Pd-catalyzed halocyclizations of unactivated 1,6-diynes through a formal anti-carbopalladation/bromide radical cascade

We report a Pd-catalyzed halocyclization of unactivated 1,6-diynes with N-bromosuccinimide (NBS). This approach produces stereo-defined dibromo substituted dihydropyrans, tetrahydropyridines, and 3-methylene cyclohexenes with exocyclic double bond appendages in mostly good yields. Copper salt was found to be a useful Lewis acid in this reaction. Mechanistically, a formal anti-carbopalladation and a bromide radical promoted Pd^II-Pd^III-Pd^I-Pd^II catalytic cycles were proposed to be involved in the formation of the dibromo-substituted products. Further functionalization of the dihydropyran derivatives underwent B(C₆F₅)₃-catalyzed ring opening, and reduction afforded dibrominated 1,3-dienes with excellent stereoselectivity.     

Phosphine-catalyzed [4+2] cycloaddition of sulfamate-derived cyclic imines with allenoates: synthesis of sulfamate-fused tetrahydropyridines

Using n-PrPPh₂ as the nucleophilic catalyst, the [4+2] cycloaddition reaction of the sulfamate-derived cyclic imines with allenoates works efficiently to yield various sulfamate-fused tetrahydropyridines in high yields with excellent diastereoselectivities. Using amino acid-based bifunctional phosphine as chiral catalyst, an asymmetric [4+2] cycloaddition reaction was achieved, giving chiral sulfamate-fused tetrahydropyridines in high yields with good enantiomeric excesses.     

Organocatalytic Enantioselective Oxidative C?H Alkenylation and Arylation of N‐Carbamoyl Tetrahydropyridines and Tetrahydro‐β‐carbolines

The first organocatalytic enantioselective C H alkenylation and arylation reactions of N‐carbamoyl tetrahydropyridines and tetrahydro‐β‐carbolines (THCs) are described. The metal‐free processes represent an efficient and straightforward approach to a variety of structurally and electronically diverse α‐substituted tetrahydropyridines and THCs in good yields with excellent regio‐ and enantioselectivities. Preliminary control experiments provide important insights into the reaction mechanism.     

A new and stereospecific synthesis of an inositol analogue: bis-homoinositol

The photooxygenation of trans-8-(acetyloxy)bicyclo[4.2.0]octa-2,4-dien-7-yl acetate afforded the bicyclic endoperoxide. Reduction of the endoperoxide with thiourea followed by acetylation gave the corresponding tetraacetate. The KMnO₄ oxidation of the tetraacetate followed by acetylation gave dihydroxytetraacetate Ammonolysis of tetraacetate afforded the bis-homoinositol, bicyclo[4.2.0]octane-2,3,4,5,7,8-hexol.     

Stereochemistry of hydroboration of 3(or 5)-methyl-4-phenyl-1,2,5,6-tetrahydropyridines

Hydroboration of N-substituted 5 - methyl - 4 - phenyl - 1,2,5,6 - tetrahydropyridines gave, as a sole product, the 5-methyl-4-phenyl-3-piperidinols, while the 3 - methyl - 4 - phenyl - 1,2,5,6 - tetrahydropyridines gave the 3-methyl-4-phenyl-3-piperidinols together with the 4-boryl-3-methyl-4-phenylpiperidine amine boranes. Structural and configurational assignments were made through the analysis of spectral data (IR, ¹H NMR and MS).     

Syntheses of substituted 1-(2-phenethyl)pyrazoles

Alkylation of 3-methylpyrazole with 2-phenethyl p-toluenesulfonate gave 3-methyl-1-(2-phenethyl)pyrazole ( 2a ) and 5-methyl-1-(2-phenethyl)pyrazole ( 3a ) in low yield. Reaction of 5-chloro-1,3-dimethylpyrazole ( 5 ) with substituted-benzaldehydes afforded compounds 7 . Reduction of the latter afforded compound 2 in high yield. Compound 3 could be obtained from the reaction of substituted-2-(phenethyl)hydrazine hydrochloride 9 with acetoacetaldehyde dimethylacetal in moderate yield.     

Synthesis of the C-5 homologue of N-acetylneuraminic acid by enzymatic chain elongation of 2-C-acetamidomethyl-2-deoxy-D-mannose

Condensation of hexopyranosid-2-ulose 1 with nitromethane afforded after acetylation 2. Treatment with borohydride yielded stereoselectively 4. Reduction, acetylation, deblocking, and acid hydrolysis gave then C-2 branched N-acetylmannosamine 7 that was enzymatically converted to the first known C-5 branched homologue of 8.     

Benzomorphan related compounds. XIV. Synthesis of 2-(2-pyrrolylmethyl)- and 2-(2-indolylmethyl)tetrahydropyridines and cyclization to pyrrolo[3,2-f]morphans

The synthesis of 2-{2-pyrrolylmethyl)- and 2-(2-indolylmethyl)tetrahydropyridines by condensation of 2-cyanopyridines with appropriate pyrrole or indole derivatives followed by ketone reduction, quaternization and sodium borohydride reduction are described. The acid-induced cyclization of 2-(2-pyrrolylmethyl)tetrahydropyridines affords 4,5,6,7,8,9-hexahydro-4,8-methanopyrrolo[2,3-d]azocine systems (pyrrolo[3,2-f]-morphans), although the method fails with N-benzyl substituted pyrroles. The acid treatment of 2-(2-indolylmethyl)tetrahydropyridines and of 2-indolyl tetrahydro-2-pyridyl ketones is not a suitable procedure for the preparation of indolo[3,2-f]morphans, because of the protonation of indole nucleus or carbonyl group, respectively.