N-acyliminium Ion Precursors Research Articles

N-Acyliminium Ion Chemistry: Improving the Access to Unsaturated γ-Lactams and Their N-α-Methoxylated Derivatives: Application to an Expeditive Synthesis of (±)-Crispine A

An improved synthesis of unsaturated γ-lactams by condensation of various primary amines with 2,5-dimethoxy-2,5-dihydrofuran is described. A modified mechanism for this reaction is suggested. Synthesis of their N-α-methoxylated derivatives, as N-acyliminium ion precursors, is also reported. Finally, a short synthesis of (±)-crispine A is presented as an illustrative application.

Exocyclic N-Acyliminium Ion (NAI) Cyclization: Access to Fully Substituted Oxazoles and Furocoumarins.

A concise, one-pot route to oxazoles and furocoumarins has been reported. The key step in this transformation involves in situ generation of N-acyliminium ion (NAI) precursor under catalyst and solvent-free conditions and their further transformations promoted by superacid in the same pot. We have also presented the experimental evidence for the involvement of proto-solvated novel exocyclic N-acyliminium ion. Further, the UV-visible and fluorescence studies revealed that few of the compounds reported here exhibited emission of blue light upon irradiation in EtOH in the region of 404-422 nm.

Recent synthetic applications of α-amido sulfones as precursors of N-acylimino derivatives

α-Amido sulfones can be directly used as N-acylimine or N-acyliminium ion precursors in several synthetic processes aimed at the preparation of nitrogen containing compounds. This review collects the most relevant and practical utilizations of α-amido sulfones appeared in the literature after 2005.

Trapping of N-Acyliminium Ions with Enamides: An Approach to Medium-Sized Diaza-Heterocycles.

Enamides equipped with N-acyliminium ion precursors were obtained through reduction of ynamides tethered to N-imides. Intramolecular TMSOTf-mediated trapping of N-acyliminium ions provided a variety of polyfunctionalized medium-sized diaza-heterocycles of putative pharmacological interest.

Microwave-Assisted Branching Cascades: A Route to Diverse 3,4-Dihydroquinazolinone-Embedded Polyheterocyclic Scaffolds.

A novel metal-free microwave-assisted branching cascades strategy for the efficient synthesis of 3,4-dihydroquinazolinone-embedded polyheterocyclic scaffolds is reported. Starting from in situ generated key N-acyliminium ion precursors, 12 distinct and skeletally diverse polycyclic frameworks were accessed in a single step/pot via adjustment of the nucleophile(s) and reaction conditions. Postcascade functionalization of these compounds was also demonstrated, proving the utility of this method in accessing structurally diverse chemical entities.

Synthesis of Bridged Heterocycles via Sequential 1,4- and 1,2-Addition Reactions to α,β-Unsaturated N-Acyliminium Ions: Mechanistic and Computational Studies.

Novel tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of allyl and 3-substituted allylsilanes to indolizidine and quinolizidine α,β-unsaturated N-acyliminium ions. These reactions involve a novel N-assisted, transannular 1,5-hydride shift. Such a mechanism was supported by examining the reaction of a dideuterated indolizidine, α,β-unsaturated N-acyliminium ion precursor, which provided specifically dideuterated tricyclic bridged heterocyclic products, and from computational studies. In contrast, the corresponding pyrrolo[1,2-a]azepine system did not provide the corresponding tricyclic bridged heterocyclic product and gave only a bis-allyl adduct, while more substituted versions gave novel furo[3,2-d]pyrrolo[1,2-a]azepine products. Such heterocyclic systems would be expected to be useful scaffolds for the preparation of libraries of novel compounds for new drug discovery programs.

Dual Hard/Soft Gold Catalysis: Intermolecular Friedel–Crafts‐Type α‐Amidoalkylation/Alkyne Hydroarylation Sequences by N‐Acyliminium Ion Chemistry

Gold catalysts have been applied in cascade-type reactions for the synthesis of different nitrogen-based compounds. The reactions likely proceed by a new gold-catalyzed cascade intermolecular α-amidoalkylation/intramolecular carbocyclization cascade process by unifying both the σ- and π-Lewis acid properties of the gold salts. In the first part of this report we show that the σ-Lewis acidity of gold(I) and gold(III) could be exploited to efficiently catalyze the nucleophilic substitution of various alkoxy- and acetoxylactams. The reaction was found to be applicable to a wide range of cyclic N-acyliminium ion precursors and various nucleophiles, including allyltrimethylsilane, silyl enol ethers, arenes, and active methylene derivatives. As a logical progression of this study, a combined hard/soft binary catalytic gold system was then used to implement an unprecedented tandem intermolecular Friedel-Crafts amidoalkylation/intramolecular hydroarylation sequence allowing an expedient access to new, complex, fused polyheterocyclic structures from trivial materials.

Enantioselective, Thiourea‐Catalyzed Intermolecular Addition of Indoles to Cyclic N‐Acyl Iminium Ions

Enantioselective, Thiourea‐Catalyzed Intermolecular Addition of Indoles to Cyclic <i>N</i>‐Acyl Iminium Ions

N,N-Acetals as N-Acyliminium Ion Precursors: Synthesis and Absolute Stereochemistry of Epiquinamide

A stereoselective synthesis of (+)-epiquinamide is presented in combination with determination of the absolute configuration of the natural product. Key steps in the sequence involved chemoenzymatic formation of an enantiomerically pure cyanohydrin, reductive cyclization to the corresponding cyclic N,N-acetal, and subsequent conversion into a suitable N-acyliminium ion precursor to enable construction of the second ring.

Scope and limitations of the solution and solid phase synthesis of homoallylic amines via N-acyliminium ion reactions

The full scope and limitations of solution and solid phase one-pot three component N- acyliminium ion reactions are detailed. After studying the scope in solution with respect to the carbamate, nucleophile and aldehyde component, a 'translation' was made to the solid phase. The solid phase reactions were eventually carried out using the so-called SEC linker system, which was previously developed in our group. In order to maximize the scope of the nucleophile component, additional studies were successfully conducted using two-step processes involving stable N-acyliminium ion precursors.

Chiral Glycine Cation Equivalents: N‐Acyliminium Species Derived from Diketopiperazines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Allenylmethylsilanes as Nucleophiles in N‐Acyliminium Ion Chemistry.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Cyclopentene‐Fused Pyrroloisoquinolinone Derivative via N‐Acyliminium Ion Cyclization.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chiral glycine cation equivalents: N-acyliminium species derived from diketopiperazines

Studies towards a N,N′-bis(p-methoxybenzyl)diketopiperazine asymmetric glycine cation equivalent for the synthesis of homochiral α-amino acids are described. The oxidation of enolate 3 with molecular oxygen provides either a mixture of hydroxylated diketopiperazines 7 and 8 or trione 10 depending upon the reaction conditions. The nucleophilic reduction of trione 10 and the reaction of acetoxy N-acyliminium ion precursors 5 and 6, derived from 7 and 8, with allyltrimethylsilane and boron trifluoride etherate is examined and a model for the stereoselectivity observed in these additions is presented.

Allenylmethylsilanes as nucleophiles in N-acyliminium ion chemistry.

Treatment of a variety of N-acyliminium ion precursors with 2,3-butadienyl(trimethyl)silane and related allenes in the presence of BF(3).OEt(2) provides good yields of N-protected 2-(aminomethyl)-substituted 1,3-dienes, which prove to be useful substrates for subsequent Diels-Alder and alkene metathesis reactions. [reaction: see text]

SYNTHESIS OF CYCLOPENTENE-FUSED PYRROLOISOQUINOLINONE DERIVATIVE VIA N-ACYLIMINIUM ION CYCLIZATION

ABSTRACT In this research, a new class of pyrrolo[2,1-a]isoquinolinone derivative 7 was prepared. C-4 Hydroxylated 5-ethoxylactam 1b gave 4,5-epoxylactam 2 in high yield instead of isoquinoline derivative 3b under the N-acyliminium ion cyclization condition. The 4,5-epoxylactam 2 was converted to another N-acyliminium ion precursor 6 through base-promoted epoxide ring opening, silylation, and thermal Diels–Alder reaction with cyclopentadiene in high yield. Finally, compound 6 was cyclized in the presence of TiCl4 to provide cyclopentene-fused pyrroloisoquinoline derivative 7.

Building constrained peptidomimetics: a convenient approach to 3-phenyl-5-vinyl substituted proline derivatives

An approach to the synthesis of 3-phenyl-5-vinyl substituted prolines starting from readily available 2,3-disubstituted pentenoic acid derivatives is reported. The route converts the pentenoic acid derived starting materials into cyclic N-acyliminium ion precursors with the use of a hydroboration–Swern oxidation sequence. This overall transformation worked best when the initial alkylborane product was treated sequentially with excess MCPBA and then acetone prior to the Swern oxidation. In this way, a 70% yield of the desired N-acyliminium ion precursor could be obtained. Once in hand, the cyclic N-acyliminium ion precursor was used to make the desired 3-phenyl-5-vinyl substituted prolines.

N -Acyliminium ion chemistry and palladium catalysis: a useful combination to obtain bicyclic heterocycles

Abstract By using N-acyliminium ion chemistry, several ω-propadienyllactams and a propadienyloxazolidine were prepared from N-acyliminium ion precursors and propargylsilanes. Treatment of these allene containing lactams and oxazolidinone with allyl halides or an allyl carbonate using Pd(II)-salts as the catalyst gave rise to a coupling–cyclization reaction, yielding bicyclic systems in which the allyl moiety is incorporated. With this methodology several substituted pyrrolizinones, an oxazolone and indolizinone were prepared.

Preparation of Resin-Bound N-(-Methoxyalkyl)amides: An Advantageous Use of Solid-Phase Chemistry for the Handling of Unstable Precursors of the Versatile N-Acyliminium Ions

The development of a new and efficient synthesis of resin-bound N-(α-methoxyalkyl)amides is described. The condensation of aldehydes on a supported amide in the presence of trimethyl orthoformate afforded, in acidic media, the resin-bound N-acyliminium ion precursors. Repeating the reaction a second time led to a great improvement in yields, demonstrating one advantage of the solid-phase chemistry for the handling of sensitive intermediates difficult to isolate.

Preparation of resin-bound N-(alpha-methoxyalkyl)amides: an advantageous use of solid-phase chemistry for the handling of unstable precursors of the versatile N-acyliminium ions.

The development of a new and efficient synthesis of resin-bound N-(alpha-methoxyalkyl)amides is described. The condensation of aldehydes on a supported amide in the presence of trimethyl orthoformate afforded, in acidic media, the resin-bound N-acyliminium ion precursors. Repeating the reaction a second time led to a great improvement in yields, demonstrating one advantage of the solid-phase chemistry for the handling of sensitive intermediates difficult to isolate.