Rh(II)-catalyzed [2,3]-sigmatropic rearrangement of sulfur ylides derived from N-tosylhydrazones and sulfides

In this paper, Rh₂(OAc)₄-catalyzed [2,3]-sigmatropic rearrangement of sulfur ylides derived from N-tosylhydrazones and sulfides is reported. A series of tosylhydrazones derived from aldehydes were successfully used for [2,3]-sigmatropic rearrangement by reaction with either allylic phenyl sulfides or propargyl phenyl sulfides. The reaction conditions were optimized and afforded the products in moderate to good yields. In addition, a novel and convenient approach for the synthesis of cyclobutenones and cyclopropanes has been developed through direct oxidation of the rearrangement products.     

Approaches to the enantioselective synthesis of ferrugine and its analogues

A four-step synthetic route, to ferrugine (2α-benzoyltropane), its methyl analogue (2-acetyltropane) and their N-benzyl analogues is reported. The reaction sequence uses tropinone or N-benzylnortropinone aldols as key intermediates. Reduction of aldol derived N-tosylhydrazones and oxidation of the side chain hydroxyl group followed by spontaneous diastereomer equilibration provides the final products. Relative configuration of the exo,anti N-methyl and N-benzyl aldols was retained during N-tosylhydrazone formation. The relative stereochemistry of N-tosylhydrazones was assigned by single crystal diffraction. The final products, ferrugine and its methyl analogue, were synthesized in enantiomerically pure form via asymmetric deprotonation of tropinone using chiral lithium amide/lithium chloride aggregate prepared in situ from (S,S)-N,N-bis(1-phenylethyl)amine hydrochloride.     

White Light/NIS-Promoted Aminoselenylation of Alkenes by Using N-Tosylhydrazones

A white light/iodosuccinimide (NIS)-promoted three component reaction of alkenes, N-sulfonylhydrazones, and diorganyl diselenides for synthesis of organylselenylethyl sulfonylhydrazones under air is disclosed. This intermolecular aminoselenylation of alkenes using N-tosylhydrazones as nitrogen source was performed under mild conditions and well tolerated for common groups. In addition, heteroaryl and aliphatic diselenides also gave the target compounds. Gram-scale reaction also carried out smoothly. This protocol has a wide range of substrates and affords moderate to high yields and excellent regioselectivities. The photoactive intermediates from the interaction between NIS and diphenyl diselenide was detected by UV-visible absorption spectra, which matches the wavelength of the applied white LED. A reasonable mechanism was proposed based on UV-visible light experiments and control experiments.     

Metal free coupling of heteroaryl N-tosylhydrazones and thiols: Efficient synthesis of sulfides

A metal free coupling of heteroaromatic N-tosylhydrazones with thiols is presented. A convenient synthetic route to synthesize heteroaryl N-tosylhydrazones is also showed. Valuable thioethers with pyrroles, pyridines, thieno[2,3-b]pyridines, imidazo[1,2-a]pyridines, and 6H-thieno[2,3-b]pyrroles derivatives were synthesized in good yields. This coupling reaction can be carried out in a one-pot fashion and scaled up to the gram scale by using heteroaryl aldehydes, without the need to isolate the N-tosylhydrazone.     

The Pd-catalysed asymmetric allylic alkylation reactions of sulfamidate imines

The Pd-catalysed asymmetric allylic alkylation (Pd-AAA) of prochiral enamide anions derived from 5H-oxathiazole 2,2-dioxides has been developed. Various 4,5-disubstituted and 4-substituted cyclic sulfamidate imines have participated in the transformation with a range of allyl carbonates—as well as 2-vinyl oxirane, 2-vinyl-N-tosylaziridine, and 2-vinyl-1,1-cyclopropane dicarboxylate—to furnish the desired C-allylated products in moderate to high yields, with high regioselectivites and generally high enantioselectivities. Conversion between N- and C-allyl products was observed, with the N-allylated products converting to the C-allylated products over time. The resulting high-value allylated heterocyclic products all bear a tetrasubstituted stereogenic centre and can be reduced to an allylated chiral sulfamidate or an amino alcohol.

The Pd-catalysed asymmetric allylic alkylation (Pd-AAA) of prochiral enamide anions derived from 5H-oxathiazole 2,2-dioxides has been developed.     

Efficient synthesis of N-allylated 2-nitroiminoimidazolidine analogues from Baylis–Hillman bromides

Various Baylis–Hillman–derived new N-allylated 2-nitroiminoimidazolidine analogs were efficiently prepared using potassium carbonate as base. Simple workup procedure, excellent yields, and mild reaction conditions are the salient features of this method. All the synthesized compounds are screened for their larvicidal activity on fourth instar mosquito larvae, Culex quinquefasciatus.     

Metal-free and highly regioselective synthesis of N-heteroaryl substituted pyrazoles from α,β-unsaturated N-tosylhydrazones and heteroaryl chlorides

A cascade cyclization/nucleophilic aromatic substitution (S_NAr) reaction of α,β-unsaturated N-tosylhydrazones with N-heteroaryl chlorides was developed for the synthesis of N-heteroaryl pyrazole derivatives. This one-pot reaction provided bi(heteroaryl) derivatives in good to excellent yields and with excellent regioselectivity. The procedure is operationally simple and applicable to large-scale synthesis.     

Transition‐Metal‐Free Synthesis of N‐(1‐Alkenyl)imidazoles by Potassium Phosphate‐Promoted Addition Reaction of Alkynes to Imidazoles

The addition reaction of alkynes to N‐heterocycles by simply heating in DMSO with potassium phosphate is reported. Good yields with high stereoselectivity could be achieved for a range of substrates. The scope is quite general for both amines and phenylacetylenes. In addition, internal alkynes and α‐bromostyrene were also examined in this reaction. This process is efficient and useful for the synthesis of (Z)‐N‐(1‐alkenyl)imidazoles and related Z products. Thus, the reaction is useful because of the importance of the imidazole scaffold.     

A Modular Approach to Dibenzo-fused ϵ-Lactams: Palladium-Catalyzed Bridging-C−H Activation

Tricyclic ring systems possessing a dibenzo structure joined to a seven-membered heterocyclic ring frequently show important biological activities. However, a modular approach to these molecules based on efficient intermolecular reaction of readily available chemicals is lacking. Herein, an unprecedented palladium-catalyzed formal [4+3] annulation for modular construction of these tricyclic systems is described. This reaction features easily accessible reactants (o-haloarylaldehydes and N-tosylhydrazones), broad substrate scope, and excellent functional group compatibility. The synthetic potential is demonstrated by the easy scale-up reactions, late-stage modification of complex molecules, and collective synthesis of bioactive molecules and approved drugs.     

Enantioselective Radical-Polar Crossover Reactions of Indanonecarboxamides with Alkenes

Highly efficient asymmetric intermolecular radical-polar crossover reactions were realized by combining a chiral N,N′-dioxide/Ni^II complex catalyst with Ag₂O under mild reaction conditions. Various terminal alkenes and indanonecarboxamides/esters underwent radical addition/cyclization reactions to afford spiro-iminolactones and spirolactones with good to excellent yields (up to 99 %) and enantioselectivities (up to 97 % ee). Furthermore, a range of different radical-mediated oxidation/elimination or epoxide ring-opening products were obtained under mild reaction conditions. The Lewis acid catalysts exhibited excellent performance and precluded the strong background reaction.     

Visible Light Induced Brønsted Acid Assisted Pd-Catalyzed Alkyl Heck Reaction of Diazo Compounds and N-Tosylhydrazones

A mild visible light-induced palladium-catalyzed alkyl Heck reaction of diazo compounds and N-tosylhydrazones is reported. A broad range of vinyl arenes and heteroarenes with high functional group tolerance, as well as a range of different diazo compounds, can efficiently undergo this transformation. This method features Brønsted acid-assisted generation of hybrid palladium C(sp³)-centered radical intermediate, which allowed for new selective C?H functionalization protocol.     

Cu(I)-catalyzed cascade reaction of N-tosylhydrazones with 3-butyn-1-ol: A new synthesis of tetrahydrofurans

The Cu(I)-catalyzed cascade coupling/cyclization reaction of N-tosylhydrazones with 3-butyn-1-ol has been explored. This new strategy represents a simple platform for the synthesis of tetrahydrofurans in moderate to good yields.     

Synthesis of N‐Arylated 1,2‐Dihydroheteroaromatics Through the Three‐Component Reaction of Arynes with N‐Heteroaromatics and Terminal Alkynes or Ketones

The reaction of benzynes with N‐heteroaromatics including quinolines, isoquinolines, and pyridines and various terminal alkynes or ketones with an α‐hydrogen in the presence of KF and 18‐crown‐6 in THF at room temperature for 8 h gave various N‐arylated 1,2‐dihydroheteroaromatics in good to moderate yields. Some of these product structures are found in various naturally occurring and biologically active heterocyclic compounds. The reaction involves an unusual multiple construction of new C? C, C? N, and C? H bonds and the cleavage of a C? H bond in one pot. It is likely that the three‐component coupling proceeds through the nucleophilic addition of quinoline to benzyne, which generates a zwitterionic species. The latter then attracts a proton from terminal alkyne (or ketone) to generate an N‐arylated quinolinium cation and an acetylide anion. Further reaction of these two ions provides the final substituted 1,2‐dihydroquinolines. In the reaction, the terminal alkyne acts first as a proton donor and then as a nucleophile. The application of a three‐component coupling reaction product, 1,2‐dihydro‐2‐pyridinyl alkyne in a stereospecific [4+2] Diels–Alder cycloaddition reaction with N‐phenyl maleimide to give an isoquinuclidine derivative, an important core present in various natural products, is demonstrated.     

Enantioselective Radical‐Polar Crossover Reactions of Indanonecarboxamides with Alkenes

Highly efficient asymmetric intermolecular radical‐polar crossover reactions were realized by combining a chiral N,N′‐dioxide/Ni^II complex catalyst with Ag₂O under mild reaction conditions. Various terminal alkenes and indanonecarboxamides/esters underwent radical addition/cyclization reactions to afford spiro‐iminolactones and spirolactones with good to excellent yields (up to 99 %) and enantioselectivities (up to 97 % ee). Furthermore, a range of different radical‐mediated oxidation/elimination or epoxide ring‐opening products were obtained under mild reaction conditions. The Lewis acid catalysts exhibited excellent performance and precluded the strong background reaction.     

Catalytic CN Bond Alkynylation of N‐Benzylic Sulfonamides with Terminal Alkynes

A new cross‐coupling reaction of N‐benzylic sulfonamides with terminal alkynes for the synthesis of internal alkynes is reported. In the presence of 5 mol% of (Tf)₂NH/Bi(OTf)₃ (1:1), a broad range of N‐benzylic sulfonamides react smoothly with arylacetylenes to afford structurally diverse internal alkynes in moderate to excellent yields. We reasoned that vinyl cations could be formed by the regioselective attack of terminal alkynes with benzyl cations generated in situ from N‐benzylic sulfonamides under acidic conditions, which then eliminated to form a carbon‐carbon triple bond.     

Nickel Acetylacetonate-Induced 1,4-Additions of 1-Alkenyl(Disiamyl)Boranes to α,β-Unsaturated Ketones,Esters and Nitriles

The conjugate addition of 1-alkenyl(disiamyl)boranes to α,β-unsaturated ketones, esters, or nitriles was carried out in the presence of Ni(acac)₂ and triethylamine in DMF. The reactions provided γ,δ-unsaturated ketones, esters, and nitriles in high yields while retaining the original configuration of the 1-alkenylboranes. A similar addition reaction of 1-alkenyl(disiamyl)boranes to 1-acetyl-2-vinylcyclopropane produced the terminal and internal coupling products, 5,8-alkadien-2-on and 5-ethenyl-6-alken-2-on, in high yields in some cases with high regioselectivity favoring the terminal addition products.     

Photosolvolysis of 2-Allylated Anilines to 2-Indanols

It is shown that 2-allylated anilines (cf. Schemes 2–4, 7, and 8) on irradiation in protic solvents such as H₂O. MeOH, and EtOH in the presence of H₂SO₄ undergo a novel photosolvolysis reaction to yield specifically trans-2-hydroxy- and trans-2-alkoxy-1-methylindanes. Intermediates are presumably tricyclo[4.3.0.0^1,8]nona-2,4-dienes formed in an intramolecular [2s + 2s] cycloaddition reaction (cf. Scheme 7). On the other hand, N,N,N-trimethyl-2-(1′-methylallyl)anilinium salts 18 (Scheme 6) and 2-(3′-butenyl)-N,N-dimethylaniline ( 17 ) lose on irradiation in MeOH or H₂SO₄/MeOH the ammonium group reductively to yield (1-methylallyl)benzene ( 19 ) and 1-methylindane ( 20 ), respectively.     

Z-Selective synthesis of o-bromoacetophenone N-tosylhydrazones and formation of 3-methylindazoles in aqueous ethanol

A practical and effective Z-selective synthesis of o-bromoacetophenone N-tosylhydrazones is developed. Subsequent cyclization of Z-tosylhydrazones to furnish 3-methylindazoles is accomplished with the aid of copper and DMEDA in aqueous ethanol. Cyclization reactions are complete at ambient temperature in 10 min to afford the desired compounds in excellent yields.     

Hypervalent Iodine(III)‐Mediated Benzannulation of Enamines with Alkynes: an Efficient Synthesis of Substituted Aminonaphthoic Acid Derivatives

An intermolecular two C? C bond formation procedure for the synthesis of carbocycles mediated by hypervalent iodine(III) reagents was developed. This metal free protocol provided a new approach for the synthesis of useful substituted 1‐amino‐2‐naphthoic acid derivatives via benzannulation reactions. Various N‐unsubstituted and N‐alkyl substituted aromatic enamines with terminal alkynes and non‐terminal alkynes can be converted into corresponding 1‐amino‐2‐naphthoic acid derivatives under mild reaction conditions. When meta‐substituted phenyl enamines were employed in the reaction, two cyclization paths were detected in the reaction and ortho‐cyclization products were the only or major products. Good functional group tolerance, readily available material and high atom utilization efficiency make this method a potential procedure which may find broad application in organic synthesis.     

Iodine-catalyzed direct allylation of chiral oxazolidinones by the amide-aldehyde-alkene condensation

An iodine-catalyzed direct allylation of chiral oxazolidinones with aldehydes and alkenes has been developed. The reaction proceeds, without use of any bases or metals, directly converted the 3-chiral oxazolidinones into N-allylated oxazolidinones. Additionally, the 3-chiral allylamine skeleton was constructed and the diastereomers were isolated by simple column chromatography.