New strategies for the synthesis of 1- and 2-azetines and their applications as value-added building blocks

Gatazka, Michael; McFee, Elvis C; Ng, Cody; Wearing, Emily; Schindler, Corinna S.

doi:10.1039/d2ob01812h

Cited by 13 publications

(6 citation statements)

References 141 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We recently developed an intramolecular visible-light-mediated [2 + 2]-cycloaddition of alkenes 14 , which resulted in the formation of azetidines 15 upon sensitization of the 2-isoxazoline moiety (Figure A) . On the basis of these results, we expected alkyne 16 to react analogously to form 2-azetine , 17 upon irradiation with visible light in the presence of an iridium photocatalyst (Figure B). To our surprise, the reaction resulted in the exclusive formation of a new product in 34% yield, which was ultimately characterized as the dimeric, macrocyclic 1-azetine 18 .…”

Section: Resultsmentioning

confidence: 99%

Visible-Light-Mediated Macrocyclization for the Formation of Azetine-Based Dimers

Ng,

Kim,

Kevlishvili

et al. 2024

ACS Catal.

Self Cite

View full text Add to dashboard Cite

Macrocyclic dimeric lactones have pharmacological activities that make them attractive synthetic targets, but typical synthetic strategies employ an iterative approach to construct the macrocycle. Herein, we report a visible-light-mediated approach that enables facile access to 1-and 2-azetine-based dimeric lactones of up to 30-membered ring macrocycles. These products form via four consecutive triplet energy transfers for 1-azetine dimeric products and two consecutive triplet energy transfers for 2-azetine dimeric products. Computational investigations provide insights into the mechanism of this reaction, consistent with an unexpected initial intermolecular [2 + 2]-cycloaddition being preferred under nonstandard Curtin−Hammett conditions over the corresponding intramolecular reaction, which ultimately enables an efficient reaction pathway for macrocyclic dimerization.

show abstract

Section: Resultsmentioning

confidence: 99%

Visible-Light-Mediated Macrocyclization for the Formation of Azetine-Based Dimers

Ng,

Kim,

Kevlishvili

et al. 2024

ACS Catal.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cyclobutanes were similarly obtained from metallated bicyclo[1.1.0]butanes 23 – 27 . Aside from strain-releasing strategies, substituted azetidines and cyclobutanes are traditionally approached through [2 + 2]-cycloadditions as recently illustrated by Schindler 28 – 31 , Bach 32 – 35 , Glorius 36 – 38 and Brown 39 – 43 as well as cyclizations and ring contraction and expansion reactions 44 – 50 , which imply a pre-organization of the substituents around the structure of starting materials.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective polar radical crossover for the functionalization of strained-ring systems

Trauner,

Ghazali,

Rettig

et al. 2024

Commun Chem

View full text Add to dashboard Cite

Radical-polar crossover of organoborates is a poweful tool that enables the creation of two C-C bonds simultaneously. Small ring systems have become essential motifs in drug discovery and medicinal chemistry. However, step-economic methods for their selective functionalization remains scarce. Here we present a one-pot strategy that merges a simple preparation of strained organoboron species with the recently popularized polar radical crossover of borate derivatives to stereoselectively access tri-substituted azetidines, cyclobutanes and five-membered carbo- and heterocycles.

show abstract

“…Among these strategies, the manipulation of 2‐azetines is emerging as a powerful tool to decorate the azetidine ring. Indeed, 2‐azetines have been recently adopted as versatile synthetic platforms to access functionalized azetidines through cycloadditions, [9] batch and flow metal catalyzed hydrogenations, [10,11] acid [10b] and base‐promoted [12] additions, and metal‐catalyzed transformations [13,14] …”

Section: Introductionmentioning

confidence: 99%

Forging C−S Bonds on the Azetidine Ring by Continuous Flow Photochemical Addition of Thiols and Disulfides to Azetines

Colella,

Gelato,

Andresini

et al. 2023

Eur J Org Chem

View full text Add to dashboard Cite

A strategy for anti‐Markovnikov hydroalkyl/aryl thiolation and disulfidation of 2‐azetines under continuous flow conditions has been developed. Thiyl radicals are generated from thiols or disulfides and subsequently propagate into the azetine unsaturation to forge the C−S bond and shape a secondary radical intermediate. This carbon‐centered radical chain transfers to another thiol via hydrogen atom transfer (HAT) or another disulfide to regenerate the key thiyl radical intermediates. The use of flow technology ensures efficient irradiation of the reaction mixture leading to extremely fast, robust, and scalable protocols. Furthermore, ethyl acetate was adopted as an environmentally responsible solvent.

show abstract

New strategies for the synthesis of 1- and 2-azetines and their applications as value-added building blocks

Abstract: Azetines are valuable 4-membered nitrogen-containing heterocycles with unique reactivity and useful synthetic applications. Recent methods to access these compounds and a comprehensive review of their application as intermediates is presented.

Cited by 13 publications

References 141 publications

Visible-Light-Mediated Macrocyclization for the Formation of Azetine-Based Dimers

Visible-Light-Mediated Macrocyclization for the Formation of Azetine-Based Dimers

Stereoselective polar radical crossover for the functionalization of strained-ring systems

Forging C−S Bonds on the Azetidine Ring by Continuous Flow Photochemical Addition of Thiols and Disulfides to Azetines

Contact Info

Product

Resources

About