Regioselective Ring Opening Of Aziridines Research Articles

Enantioselective Total Synthesis of (-)-Hunterine A Enabled by a Desymmetrization/Rearrangement Strategy.

The first enantioselective total synthesis of (-)-hunterine A is disclosed. Our strategy employs a catalytic asymmetric desymmetrization of a symmetrical diketone and subsequent Beckmann rearrangement to construct a 5,6-α-aminoketone. A convergent 1,2-addition joins a vinyl dianion nucleophile and the enantioenriched ketone. The endgame of the synthesis features an aza-Cope/Mannich reaction and azide-olefin dipolar cycloaddition to complete the pentacyclic ring system. The synthesis is completed through a regioselective aziridine ring opening.

Synthesis of Phenethylamine‐Azulene Conjugates Enabled by Regioselective Ring Opening of Aziridines

AbstractThe BF3⋅OEt2‐catalyzed reaction of azulene with N‐protected aziridines represents a general, efficient (up to 91% yield) and regioselective approach to phenethylamine‐azulene conjugates. Stereochemical studies and DFT calculations lend support to a concerted SN2‐type mechanism governing the ring‐opening of the aziridine.

Catalyst- and solvent-free regioselective ring opening of aziridines with amines: application in the gram-scale synthesis of the α,β-diamino propionic derivative, aspergillomarasmine A.

A green and efficient approach for synthesizing α,β-diamino propionic derivatives was developed through the ring opening of α-C-alkyloxycarbonyl aziridine. This method features catalyst- and solvent-free conditions, high regioselectivity, and wide substrate scope including solid amines, and realizes the gram-scale synthesis of aspergillomarasmine A.

Synthesis of Fingolimod Employing Regioselective Aziridine Ring-Opening Reaction as a Key Step

Synthesis of Fingolimod Employing Regioselective Aziridine Ring-Opening Reaction as a Key Step

Zinc-Catalyzed Hydroxyl-Directed Regioselective Ring Opening of Aziridines in SN2 Reaction Pathway

In this protocol, a zinc-catalyzed catalytic regioselective ring opening of electronically and sterically unbiased 2,3-aziridinyl alcohols has been accomplished. The directing effect of the hydroxy...

Total Synthesis of Pactalactam, an Imidazolidinone-Type Pactamycin Analogue.

The first total synthesis of pactalactam was accomplished using substrate-controlled stereoselective aziridination and regioselective aziridine ring-opening to construct three continuous amino groups on an octasubstituted cyclopentane core. The cyclopentane framework was obtained by ring-closing metathesis and aldol coupling using a l-threonine-derived oxazoline compound. Cyclic urea formation, m-acetylphenyl group introduction by Chan-Lam coupling, and primary alcohol-selective acylation yielded the reported pactalactam structure. The presence of pactalactam in the fermentation broth of pactamycin-producing bacteria was also confirmed.

Aryldiazonium ion initiated C–N bond cleavage for the versatile, efficient and regioselective ring opening of aziridines

Aryldiazonium salts have been proved to initiate the regioselective cleavage of aziridines for the installation of varied functional groups.

Synthesis of tubuphenylalanine and epi-tubuphenylalanine via regioselective aziridine ring opening with carbon nucleophiles followed by hydroboration-oxidation of 1,1-substituted amino alkenes

An efficient synthesis of N-Boc-tubuphenylalanine benzyl ester (N-Boc-Tup-OBn, 1a) and N-Boc-epi-tubuphenylalanine benzyl ester (N-Boc-epi-Tup-OBn, 1b) is reported herein. Regioselective aziridine 4 ring opening with carbon nucleophiles followed by hydroboration of 1,1-substituted aminoalkene 3 using 9-BBN and subsequent oxidation in an alkaline medium are used as the key steps to provide N-tosyl 1,4-aminoalcohols. The 1,4-aminoalcohols are successfully transformed into the desired products with an overall yield of 23% for 1a and 11% for 1b over 8 consecutive steps separately.

Synthesis of diverse β-(nitrooxy)-substituted amines by regioselective ring-opening of aziridines under neat conditions

An efficient and regioselective method was developed for the synthesis of β-(nitrooxy)-substituted amine derivatives by ring-opening of different aziridines with Zn(NO3)2·6H2O without using additives or catalyst. A library of β-(nitrooxy)-substituted amine derivatives having a variety of substituents has been synthesized. Excellent regioselectivity, high yields, clean reaction, ease of product isolation, easily accessible reactants, and solvent-free as well as environment friendly reaction conditions are the notable advantages of the present methodology. The nitrooxy derivative was successfully transformed into hydroxy derivative by simple reduction. Gram-scale synthesis demonstrates the potential applications of the present method.

Preparation of Chiral Contiguous Epoxyaziridines and Their Regioselective Ring-Opening for Drug Syntheses.

Synthetically valuable chiral (aziridin-2-yl)oxirane-3-carbaldehydes bearing three consecutive functional groups including aziridine, epoxide, and aldehyde were prepared from the stereoselective epoxidation of (aziridin-2-yl)acrylaldehydes with H2 O2 using organocatalyst (2R)- or (2S)-[diphenyl(trimethylsilyloxy)methyl]pyrrolidine as organocatalyst. The regioselective ring opening of aziridines and epoxides enabled us to achieve the highly efficient asymmetric synthesis of the antibiotic edeine D fragment 3-hydroxy-4,5-diaminopenatanoic acid, an intermediate for the formal synthesis of non-proteinogenic amino acid (-)-galantinic acid, and for potent antifungal agent (+)-preussin, and the medicinally important framework 3-hydroxy-2-hydroxymethylpyrrolidine.

Diastereoselective synthesis ofcis-1,3-disubstituted isoindolinesviaa highly site-selective tandem cyclization reaction

A highly site-selective tandem reaction involving regioselective ring opening of aziridines and Michael addition of electron-deficient alkenes has been described.

A Mild and Efficient Method for the Syntheses and Regioselective Ring-Opening of Aziridines

We have developed a new synthetic method for the synthesis of aziridines using Chloramine-T as an effective reagent in the presence of NH2OH·HCl and NaIO4. We found that the same combination of NH2OH·HCl and NaIO4 is also very effective for nucleophilic ring opening of aziridines.

Concise Synthesis of 3-(Aminomethyl)pyrrolizidines via an In(OTf)3-Mediated Ring Rearrangement of 2-[2-(1-Pyrrolin-2-yl)-alkyl]aziridines

In this study, an efficient ring rearrangement of 2-[2-(1-pyrrolin-2-yl)alkyl]aziridines, prepared from 2-(bromomethyl)aziridines, toward novel trans- and cis-3-aminomethyl-substituted pyrrolizidines was developed. To that end, addition of In(OTf)3 as an appropriate Lewis acid catalyst resulted in the formation of intermediate pyrrolizidinium salts via regioselective aziridine ring opening, which were then trapped by a hydride or cyanide nucleophile. Column chromatographic purification allowed the isolation of the major trans-isomers, exclusively.

Activation of Alkynylzinc Reagents by a Hemiaminal‐Driven Catalytic Microenvironment

1,2‐Aziridinyl propargylic amines have been obtained through a zinc‐catalyzed multicomponent reaction. This process relies on the dimeric amino aldehyde assembly orchestrating the intramolecular 1,2‐alkyne addition to an iminium ion. The resulting products can be readily elaborated through regioselective aziridine ring opening. A catalytic cycle and stereochemical rationale for the highly anti‐selective alkyne addition is proposed.

Synthesis of Lacosamide (Vimpat) and Its Derivatives from Aziridine-(2R)-carboxylate

An efficient and scalable synthesis of the antiepileptic drug (<i>R</i>)-lacosamide and its derivatives has been achieved from commercially available aziridine-(2<i>R</i>)-carboxylate in three simple sequential steps, including regioselective aziridine ring opening, debenzylation followed by acetylation in one pot, and amide formation. The advantage of this protocol is that the starting material and reagents are commercially available and a single purification by recrystallization is required after all the chemical transformations, providing the final drug in >99.9% ee.

ChemInform Abstract: Synthesis of β‐Substituted Tryptamines by Regioselective Ring Opening of Aziridines.

Functionalized tryptamines are targets of interest for development as small molecule therapeutics. The ring opening of aziridines with indoles is a powerful method for tryptamine synthesis if site selectivity can be controlled. 4-Nitrobenzyl carbamate (PNZ)-protected aziridines undergo regioselective ring opening to produce β-substituted tryptamines for a series of indoles. The PNZ-protected tryptamines can be further manipulated by PNZ removal under mild conditions.

ChemInform Abstract: Zwitterionic Imidazolium Salt: Recent Advances in Organocatalysis

AbstractReview: [50 refs.

Synthesis of β-substituted tryptamines by regioselective ring opening of aziridines

Functionalized tryptamines are targets of interest for development as small molecule therapeutics. The ring opening of aziridines with indoles is a powerful method for tryptamine synthesis if site selectivity can be controlled. 4-Nitrobenzyl carbamate (PNZ)-protected aziridines undergo regioselective ring opening to produce β-substituted tryptamines for a series of indoles. The PNZ-protected tryptamines can be further manipulated by PNZ removal under mild conditions.

Zwitterionic Imidazolium Salt: Recent Advances in Organocatalysis

Imidazole-based zwitterionic-type molten salts have been explored as a new class of organocatalyst in various chemical transformations. It is known that imidazolium motifs provide an unconventional C–H bond for bonding. It is experimentally proven that C2–H of the imidazole moiety plays a crucial role in catalyzing the reaction via electrophilic activation. This review is based on the role of imidazole-based zwitterionic-type molten salts as an organocatalyst for some useful chemical transformations in organic synthesis. One of the most important features of this catalyst is that it can easily be recovered from the reaction media. The recovered catalyst can be reused for subsequent reactions without losing its catalytic activity significantly. 1 Introduction 2 Zwitterionic-type Molten Salt Catalyzed syn-Selective Aza-Henry Reaction 3 Synthesis of 1-(Amidoalkyl)- and 1-(Carbamatoalkyl)-2-naphthols 4 Synthesis of 3-Aminoalkylated Indoles 5 Synthesis of Highly Substituted Imidazoles 6 Synthesis of 5-Substituted 1H-Tetrazoles by the Cycloaddition of Arenecarbonitriles with Sodium Azide 7 Synthesis of 4-Arylidene-2-phenyloxazol-5(4H)-ones 8 Zwitterion-Promoted Ethylene Methoxycarbonylation 9 Synthesis of 5,6-Unsubstituted 1,4-Dihydropyridines 10 Regioselective Ring Opening of Aziridines 11 Conclusions

Organocatalysis by an aprotic imidazolium zwitterion: regioselective ring-opening of aziridines and applicable to gram scale synthesis

An imidazole-based zwitterionic-salt, 4-(3-methylimidazolium)butane sulfonate (MBS), has been used as organocatalyst for regioselective ring-opening of aziridine by various nucleophiles.