Addition of carbon nucleophiles to cyclic N-acyliminium ions in SDS/water

The acid-catalyzed addition of 1,3-dicarbonyl compounds and activated olefins (silyl enol ethers and ethyl vinyl ether) to N-Boc-2-methoxypyrrolidine (1a) and N-Boc-2-methoxypiperidine (1b) in SDS/water medium is described. Good yields of the corresponding 2-substituted N-Boc pyrrolidines were generally observed from 1a while moderate yields prevailed from 1b.     

Addition of activated olefins to cyclic N-acyliminium ions in ionic liquids

Organoindate(III) ionic liquid (BMI·InCl₄) was successfully employed in the nucleophilic addition of allyltrimethylsilane, silyl enol ethers and ketene silyl acetals to in situ generated cyclic N-acyliminium ions at room temperature without the need of an external Lewis acid. The corresponding α-substituted heterocycles were obtained in good yields and the recovered ionic liquid phase could be reused at least three times.     

Addition of carbon nucleophiles to cyclic N-acyliminium and oxocarbenium ions under solvent-free conditions

The InCl₃-catalyzed addition of carbon nucleophiles to cyclic N-acyliminium and oxocarbenium ions under solvent-free conditions at room temperature is described. The corresponding α-substituted heterocycles were obtained in moderate to excellent yields.     

Nucleophilic addition of potassium organotrifluoroborates to chiral cyclic N-acyliminium ions: stereoselective synthesis of functionalized N-heterocycles

The stereoselective nucleophilic addition of potassium aryl- and alkynyltrifluoroborates to cyclic N-acyliminium ion derivatives from N-benzyl-3,4,5-triacetoxy-2-pyrrolidinone, affording the respective 5-substituted 2-pyrrolidinone is described. The products were obtained in moderate to good yields and with preference for the syn diastereomer.     

Spiro cyclisations of N-acyliminium ions involving an aromatic π-nucleophile

Spiro 2-pyrrolidin-5-ones were obtained from N-substituted succinimides by a two-step procedure, involving 5- or 6-endo-trig cyclisation of N-acyliminium ion intermediates with a tethered aromatic π-nucleophile.     

Selective amidoalkylation of cyclic enamino ketones with N-acyliminium salts of 3,4-dihydroisoquinolines

A series of cyclic enaminoketones were selectively amidoalkylated at the α-carbon in reactions with acyliminium reagents derived from 3,4-dihydroisoquinolines.     

Stereoselective synthesis of trans-2,3-disubstituted pyrrolidines via addition to N-acyliminium ions

An efficient and stereoselective synthesis of trans-2,3-disubstituted pyrrolidines is described. The intermolecular alkylation of racemic N-acyliminium ions generated in situ from the corresponding 3-substituted lactams proceeds stereoselectively and in high yield.     

Solid-phase synthesis of biarylalanines via Suzuki cross-coupling and intramolecular N-acyliminium Pictet-Spengler reactions

Solid-supported masked peptide aldehydes containing 3- or 4-iodophenylalanine residues were subjected to Pd-catalyzed Suzuki cross-coupling reactions with arylboronic acids. The biarylalanines generated were applied in intramolecular N-acyliminium Pictet-Spengler reactions. In this way, a range of pharmacologically interesting aryl-substituted pyrroloisoquinolines was obtained in excellent purity (>95%).     

Intramolecular substitution reactions involving π-nucleophiles and N-acyliminium cations generated from azetidin-2-ones

The Lewis acid-catalyzed intramolecular substitution reactions of 4-vinyloxy- or 4-acyloxy-azetidin-2-ones with nitrogen-bound allyl-, propargyl- and vinyl-silanes leading to the carbacephams or carbacephems, are reported. The formation of carbapenams was not observed. To illustrate the potential of these reactions to be carried out under solid-phase conditions, a synthesis of diastereomeric 5-vinyl-carbacephams via the cyclization/cleavage methodology was performed.     

endo-Mode cyclizations of vinylogous N-acyliminium ions as a route to the synthesis of condensed thiazolidines

endo-Mode cyclizations of vinylogous N-acyliminium ions incorporating heteroatom-based nucleophiles have been examined as a route to the synthesis of condensed thiazolidines. The scope of these reactions and stereochemical outcome are discussed and explained using quantum chemical calculations.     

Synthesis of indene derivatives via reactions of vinylidenecyclopropanes with the N-acyliminium cations generated from hydroxylactams

A novel route for the synthesis of 1H-indene derivatives via the reactions of vinylidenecyclopropanes (VCPs) with the N-acyliminium cations generated from hydroxylactams is described.     

Architecturally diverse heterocycle formation by N-acyliminium ion initiated cyclization

Enaminoesters containing a tethered indole or aryl moiety on the amine react with substituted maleic anhydrides or acryloyl chlorides to provide pyrrolinone or dihydropyridone products, respectively. The indole-tethered dihydropyridones can be induced to undergo a one-pot cyclization whereas, the indole-tethered pyrrolinone intermediates are readily cyclized with HCl. The aryl-tethered pyrrolinones or dihydropyridones can be isolated and subsequently induced to cyclize with triflic acid. This methodology culminates in the synthesis of erythrane-like and other natural products that are readily amenable to combinatorial library production.     

Addition of a 3-alkoxy allenylzinc to N-acyliminium ions: new entry to propargyl syn-1,2-aminoalcohol units

A new addition reaction of a 3-alkoxy allenylzinc reagent to N-acyliminiums prepared in situ from imines and acid halides is reported. Unlike addition onto imines or nitrones that affords the trans adducts, acetylenic syn-1,2 amino ethers are yielded with good selectivities, thus providing a new entry to propargyl syn-1,2-aminoalcohol units.     

Synthesis of N-substituted cyclic triglycines and their response to metal ions

N,N^′,N^″-Trisubstituted-cyclo-triglycines were synthesized. The major conformation of these compounds has C₃ symmetry, and the carbonyl groups and substituents on the nitrogen are inclined in the same direction. Their response to various metal ions was estimated by constructing ion-selective electrodes. Two of them responded selectively to Ca²⁺ over other cations, demonstrating that N,N^′,N^″-trisubstituted-cyclo-triglycines provide a new scaffold to act as host molecules.     

Ultrasound-assisted addition of alcohols to N-acyliminium ions mediated by In(OTf)3 and synthesis of 1,2,3-triazoles

An easy and mild approach using ultrasound-assisted reaction addition of alcohols to N-acyliminium ion mediated by Lewis acid, In(OTf)₃, allowed the synthesis of ether pyrrolidinones; next, the products were converted to 1,2,3-triazoles using click chemistry reaction conditions. The products in both reactions were afforded in moderate to good yields.     

Sonogashira/N-acyliminium ion aromatic π-cyclisation processes: access to tetra- and pentacyclic lactams

Application of the Sonogashira reaction of N-alkynylimides with 2-iodophenol or 2-iodo-N-tosylaniline affords 2-(N-alkylimino)-benzofurans and indoles in good yield. Selective partial reduction of the latter followed by treatment with TsOH generates N-acyliminium ions, which cyclise to afford tetra- and pentacyclic lactams in good yield. The latter are reduced to the analogous cyclic amines by BH₃.     

Sialylation reactions with N,N-dibenzylthiosialoside donor

A new sialyl donor, N,N-dibenzyl-protected p-toluenethiosialoside, was synthesized and its sialylation reaction was investigated. This reaction proceeded in a preactivation manner and preferred to provide β-anomeric coupling products. The β-selectivity was rationalized based on the assumption that N,N-dibenzylamino group could serve as an oriented group to activate the hydroxyl group of acceptor from β-face.     

Diastereoselective Ti-mediated preparation of bicyclic aminocyclopropanes from N-alkenyl amides

Intramolecular Ti-mediated alkene-amide couplings of a range of N-alk-3-enyl amides fitted with a substituent at the homoallylic position are described. CF₃-substituted compounds are suitable substrates and bicyclic aminocyclopropanes bearing a CF₃ group can be prepared in this way. Good diastereoselectivities can be observed depending on the substitution pattern, and best results are obtained in diethyl ether rather than in THF.     

N,N-polymethylene-bisadenine complexes with d metal ions

The reaction of N⁹,N^9′-(tri or tetramethylene)-bisadenines (Ade₂C_x; x = 3 or 4) in HCl 2 M at 50 °C with MCl₂ · 2H₂O [M = Zn(II), Cd(II)] yields outer sphere compounds like the previously described [(H-Ade)₂C₃][ZnCl₄] · H₂O (3) and [(H-Ade)₂C₃]₂[Cd₂Cl₈(H₂O)₂] · 4H₂O (4) for Ade₂C₃ and the new {[(H-Ade)₂C₄][Cd₂Cl₆(H₂O)₂] · 2H₂O}_n (5) for Ade₂C₄. On the other hand, only in case of Zn(II) complexes by changing [HCl] to 0.1 M, the inner sphere compounds [H-(Ade)₂C₃(ZnCl₃)] (6) and [H-(Ade)₂C₄(ZnCl₃)] · 1.5H₂O (7) are obtained. X-ray diffraction study of compound 6, which represents the first inner sphere complex with a N⁹,N^9′-bisadenine, shows a zwitterionic form with one adenine ring protonated at N(1) while the other ring is coordinated via N(7) to a ZnCl₃ moiety as in other alkyl-adenine derivatives. In addition, with Ade₂C₄, is also possible to obtain another inner sphere complex: [(H-Ade)₂C₄(ZnCl₃)₂] · 3H₂O (8).     

Allylstannation of N-acyliminium intermediates: a possible method for the stereocontrolled synthesis of polyhydroxypiperidines

The stereochemistry of the allylstannation of acyliminium intermediates has been examined for γ-alkoxyallyltins and γ-silyloxyallyltributyltins. In the latter case, the reaction has been shown to afford cleanly the syn adduct. Its subsequent ring-closing metathesis and dihydroxylation has allowed the highly stereoselective preparation of a 2-aryl-trihydroxypiperidine.