Iridium-catalyzed ring-opening reactions of unsymmetrical oxabenzonorbornadienes with water and alcohol nucleophiles

The iridium-catalyzed ring-opening reaction of unsymmetrical oxabenzonorbornadienes (OBD) with water and alcohol nucleophiles is reported, with the effects of various C₁-substituents explored. Electron-donating alkyl groups lead entirely to the substituted naphthol derivatives in excellent yields while substitution of the C₁ position for electron-withdrawing groups afforded ring-opened products in fair to excellent yields with excellent regioselectivity. The reaction was demonstrated to be highly regioselective for the C₂ position with no C₃ regioisomer observed in all cases. A proposed mechanism for the formation of C₂ regioisomeric ring-opened products has been included.     

Type 3 ring opening reaction of cyclopropanated oxabenzonorbornadienes with alcohol nucleophiles

The first examples of a Type 3 ring opening reaction of cyclopropanated oxabenzonorbornadiene (CPOBD) were found to occur using alcohol nucleophiles under acid catalyzed conditions, yielding seven-membered rings via ring expansion. Optimization of the reaction determined the ideal conditions to be 10?mol% pTsOH at 40?°C using excess alcohol nucleophile as the solvent. The scope of the reaction investigated diverse alcohol nucleophiles and bridgehead substituents on the CPOBD; in both cases the steric properties of the substituent was found in influence the yield of the reaction. Alternative Type 3 products were observed when the bridgehead substituent was an ethyl or hydroxymethyl group and limited examples of Type 3 products were formed using a palladium catalyst with alcohol nucleophiles. Mechanisms have been proposed for the formation of the Type 3 product as well as the alternative Type 3 products.     

Indium(III)-catalyzed intramolecular addition of silyl enolates to alkynes

In the presence of water and a catalytic amount of InBr₃, intramolecular trans-addition of silyl enolates derived from ketones and an aldehyde to alkynes proceeded smoothly to give 4 to 7-membered carbocycles bearing an acyl group. When carboxylic anhydrides were used as electrophiles instead of water, the cyclized products could be functionalized with an additional acyl group.     

Reactions of 3-R-5-nitropyridines with nucleophiles: Nucleophilic substitution vs conjugate addition

A number of 3-R-5-nitropyridines were synthesized and their reactions with various types of nucleophiles were investigated. The reaction outcome depends on the nature of a nucleophile: in case of anionic O-, N- and S-nucleophiles the previously unreported substitution of non-activated nitro group occurred while carbon nucleophiles underwent dearomatization of the pyridine ring with the formation of products of 1,2- and 1,4-addition.     

2-Aryl-3,4-dihydropyrans as building blocks for organic synthesis: ring-opening reactions with nucleophiles

An electrophilic ring-opening reaction of 2-aryl-3,4-dihydropyran with many nucleophiles, such as thiophenols, thiols, benzenesulfinic acid, resorcin, 2-methylfuran, benzamide and allyltrimethylsilane, was developed. In the presence of an appropriate catalyst, a product that contains not only a moiety of the nucleophile but also a fragment of 1,3-dicarbonyl compound was obtained.     

Isatins 3-C annulation vs ring-opening: Two different pathways for synthesis of spiro compounds via multicomponent reactions

An efficient synthesis of spiro compounds via two different pathways from the reactions of isatins, 3-phenylisoxazol-5(4H)-one (3-ethylisoxazol-5(4H)-one), and pyrazol-5-amine (6-aminopyrimidine-2,4(1H,3H)-dione) were reported. The catalyst Amberlyst-15 could be easy recycled and reused for many time without any appreciable loss in catalytic activity. The new type spiro compounds were gained through the ring-opening of isatins process. The structures of spiro[indoline-3,4′-isoxazolo[5,4-b]pyrazolo[4,3-e]pyridin]-2-one, spiro[isoxazolo[5,4-b]quino line-4,5′-pyrrolo[2,3-d]pyrimidine]-2′,4′,6′(1′H,3′H,7′H)-trione, and spiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2,6′(5′H)-dione were successfully confirmed by ¹H NMR, ¹³C NMR, HRMS, and X-ray crystal diffraction analysis.     

Regioselectivity in the reactions of polyfunctionalised pyrroles with nucleophiles

The polyfunctionalised pyrrole, 3,5-dichloro-1H-pyrrole-2,4-dicarbaldehyde reacts with secondary amines by condensation with the 2-carbaldehyde to give methylene-substituted pyrroles, while its N-alkyl derivatives undergo substitution of the 5-chloro group to give 5-substituted pyrroles.     

New facile synthesis of furan-2(3H)-ones and 2,3,5-trisubstituted furans via intramolecular Wittig reaction of acid anhydride

A new facile preparation of furan-2(3H)-ones and 2,3,5-trisubstituted furans by a sequential O-acylation/Wittig(/O-acylation) reaction has been developed. The easily accessible 2-(triphenylphosphoranylidene)-succinic acid 1-ester 3 reacted with acid chloride produced furan-2(3H)-ones 4 in good yields in the presence of DMAP via sequential O-acylation and intramolecular Wittig reaction of acid anhydride. Subsequently, the 2,3,5-trisubstituted furans 5 were prepared from furan-2(3H)-ones 4 and diverse aryl chlorides in presence of triethylamine through further O-acylation.     

Nucleophilic ring-opening of activated aziridines: A one-step method for labeling biomolecules with fluorine-18

The direct labeling of biomolecules with fluorine-18 is highly desirable. An option is the ring-opening of an activated aziridine moiety in a biomolecule using ¹⁸F-fluoride. Therefore, a series of aziridine-based model compounds and three aziridine-based biomolecules four aziridine-based model compounds were synthesized and evaluated as potential precursors for a direct one-step radiolabeling with fluorine-18. High to moderate yields of ¹⁸F-incorporation were achieved under mild labeling conditions. The influence of different activating groups, reaction temperature, solvent and base was investigated. The applicability of this method for the direct ¹⁸F-radiolabeling of biomolecules for positron emission tomography (PET) studies is illustrated with examples.     

Rhodium/zinc co-catalyzed asymmetric ring opening reactions of oxabenzonorbornadienes with carboxylic acids

The asymmetric ring opening reactions of oxabenzonorbornadienes with carboxylic acids are described. By using the complex of [Rh(COD)Cl]₂ and (S,S)-BDPP, with ZnI₂ as the co-catalyst, a range of aromatic acids and alkyl acids were utilized as nucleophiles to afford the corresponding chiral hydronaphthalene products with high enantioselectivities (84–94% ee). Thus, the present methodology has provides an effective synthetic method for the preparation of enantioenriched hydronaphthalenes.     

Straightforward synthesis of 4,5-bifunctionalized 1,2-oxazinanes via Lewis acid promoted regio- and stereo-selective nucleophilic ring-opening of 3,6-dihydro-1,2-oxazine oxides

Functionalized 1,2-oxazinanes are interesting and valuable heterocycles with potential applications in synthetic and medicinal chemistry. A straightforward strategy for quick access to unprecedented trans-4-hydroxyl-5-azido/cyano/amino 1,2-oxazinanes are developed: N-COR 3,6-dihydro- 1,2-oxazine oxides are prepared with ease from related dihydro- 1,2-oxazines and opened by nucleophiles TMSN₃, TMSCN and aryl/alkyl amines. Appropriate Lewis acid catalysts are found playing a vital role for both reaction rate and regioselectivity. The N-COR group can be removed under mild conditions to provide highly desirable NH 1,2-oxazinanes inaccessible via previous methods.     

Iridium-catalyzed asymmetric ring-opening reactions of N-Boc-azabenzonorbornadiene with secondary amine nucleophiles

Iridium-catalyzed asymmetric ring-opening reactions of N-Boc-azabenzonorbornadiene with a number of secondary amines has been developed for the first time. The reaction gave 1,2-trans-diamine derivatives in moderate to good yields with high enantioselectivity in the presence of 2.5 mol % of [Ir(COD)Cl]2 and 5 mol % of (S)-BINAP. The trans-configuration of the 1,2-diamino products was confirmed by X-ray crystallography.     

Enantioselective reactions catalyzed by phosphine oxides

The development of chiral small organic molecules that serve as Lewis base catalysts promoting highly stereoselective transformations has been the subject of intense research over the past decades. As a matter of fact, among the plethora of molecules used as Lewis bases, chiral phosphine oxides have thoroughly been overlooked by the organic synthetic community. Thus, this review focuses exclusively on Lewis base catalysis mediated by chiral phosphine oxides with emphasis on mechanistic aspects, covering most of the publications related to this field since their first use as organocatalyst in 2005 until the end of March 2019.     

Some reactions of Ni-Mo and Ni-W propargylic cations with nucleophiles

Preliminary reactions of the metal stabilized carbocationic species [(η-C₅H₅)Ni(μ-η²(Ni),η³(Mo)-HC₂CMe₂)Mo(CO)₂(η-C₅H₄Me)]⁺ BF₄⁻ (Ni-Mo) with nucleophiles are reported. The Ni-Mo cationic propargylic complex undergoes nucleophilic attack by sodium methoxide to regenerate the neutral μ-alkyne complex [(η-C₅H₅)Ni{μ-η²,η²-HC₂CMe₂(OMe)}Mo(CO)₂(η-C₅H₄Me)] (Ni-Mo), from which the stabilized carbocation was originally derived by protonation. The new complexes [(η-C₅H₅)Ni{μ-η²,η²-HC₂CMe₂(C₅H₅)}Mo(CO)₂(η-C₅H₄Me)] (Ni-Mo), which exist as an inseparable mixture of 1(c)-1,3- and 2(c)-1,3-cyclopentadienyl isomers, were also obtained. When the Ni-Mo cations were treated with potassium t-butoxide, the alkyne isomers with pendant 1(c)-1,3- and 2(c)-1,3-cyclopentadienyl groups are also formed. The μ-hydroxyalkyne complex [(η-C₅H₅)Ni{μ-η²,η²-HC₂CMe₂(OH)}-Mo(CO)(η-C₅H₄Me)] (Ni-Mo) was also isolated concurrently, and presumably arises from nucleophilic attack of fortuitously present hydroxide ions in the BuO⁻ reagent on the Ni-Mo cation. When NaBH₄ was added to the Ni-Mo propargylic, nucleophilic attack by hydride resulted and the μ-ⁱPrC₂H heterobimetallic complex [(η-C₅H₅)Ni{μ-η²,η²-HC₂Prⁱ}Mo(CO)₂(η-C₅H₄Me)] (Ni-Mo) was recovered in good yield. Small quantities of other side-products were isolated and characterized spectroscopically. Some tantalizing differences in reactivity were observed when the corresponding Ni-W stabilized carbocation was reacted with methoxide ions. When the not fully characterized solid formed by protonating [(η-C₅H₅)Ni(μ-η²,η²-{HC₂CMe₂)(OMe)}W(CO)₂(η-C₅H₄Me)] (Ni-W) was treated with methoxide ions, regioisomers (1(c)-1,3- and 2(c)-1,3-cyclopentadienyl species) of composition [(η-C₅H₅)Ni{μ-η²,η²-HC₂CMe₂(C₅H₅)}W(CO)₂(η-C₅H₄Me)] (Ni-W) were formed. Direct reaction of the pure cation [(η-C₅H₅Niμ-η²,η³-HC₂CMe₂)W(CO)₂(η-C₅H₄Me)]⁺ (Ni-W) with methoxide also generated the same 1(c)-1,3- and 2(c)-1,3-cyclopentadiene-substituted alkyne complexes. Unlike the case with the Ni-Mo complexes, the initial μ-HC₂CMe₂(OMe) species was not regenerated.     

Brønsted acid−catalyzed synthesis of tetrasubstituted allenes and polysubstituted 2H-chromenes from tertiary propargylic alcohols

A practical and environmentally benign Brønsted acid?catalyzed protocol for the preparation of all-carbon tetrasubstituted allenes, consisting in the direct S_N? addition of tri- or dimethoxy arenes or allyltrimethylsilane to tertiary propargylic alcohols, has been developed. In addition, a straightforward synthesis of densely substituted 2H-chromenes by metal-free tandem allenylation/heterocyclization reaction of methoxyphenols and tertiary alkynols is presented.     

Ring-closure reactions through intramolecular substitution of thiophenoxide by oxygen and nitrogen nucleophiles: simple stereospecific synthesis of 4,5-dihydroisoxazoles and 4,5-dihydropyrazoles

A new and simple method for the stereospecific synthesis of 3,5-disubstituted-4,5-dihydro-isoxazoles (chiral isoxazolines) from readily available oximes of chiral Michael adducts of thiophenol to chalcones is reported. An analogous reaction with the N-arylhydrazones of the Michael adduct gave nonracemic 1-(aryl)-3,5-diphenyl-4,5-dihydro-1H-pyrazoles (chiral pyrazolines), but these products are configurationally unstable. The key step of the synthesis is the ring-closure reaction, which occurs by a stereospecific intramoleculer nucleophilic substitution of thiophenoxide.     

CuI/Cu(OTf)2/DMSO system-catalyzed intramolecular oxidative cyclization of (o-alkynyl)arylketones: Efficient synthesis of 1,4-naphthoquinones

A concise and efficient method for the synthesis of 1,4-naphthoquinones has been successfully developed involving a CuI/Cu(OTf)₂/DMSO system-catalyzed intramolecular oxidative cyclization of (o-alkynyl)arylketones. The present protocol provided a novel approach to access functionalized 1,4-naphthoquinones from non-naphthoquinone precursors with good selectivity and functional group tolerance.     

Stereocontrolled concise synthesis of (±)-halosaline through intramolecular C-H amination

Total synthesis of 2-(2-hydroxyalkyl)-piperidine alkaloid (±)-halosaline is described from 7-octen-4-ol using a Rh-catalyzed chemo- and diastereo-selective intramolecular CH amination of sulfamate ester, ring-closing metathesis, and S_N2 displacement reaction of the six-membered ring sulfamidate as the key steps.     

Copper-catalyzed denitrogenative N-arylation of sulfoximines and sulfonamides with arylhydrazines

A Cu-mediated ligand-free arylation of NH-sulfoximines and sulfonamides by arylhydrazine hydrochlorides was herein demonstrated. The oxidative transformation provided an easy access towards N-aryl sulfoximines and sulfonamides in high yields (up to 93% yields) with broad functional groups tolerance (up to 36 examples). The protocol was proposed to take place through the free radical pathway based on the results of control reactions and EPR analysis.