Water—More Than Just a Green Solvent: A Stereoselective One‐Pot Access to All‐Chiral Tetrahydronaphthalenes in Aqueous Media

A facile and highly stereoselective construction of heavily functionalized chiral tetrahydronaphthalene skeletons fused with an oxazolidine moiety has been developed. The process involves an organocatalytic tandem Michael/nitrone formation/intramolecular [3+2] nitrone–olefin cycloaddition in aqueous media. Using rationally designed substrates, the reaction conditions have been optimized and the one‐pot process has been applied to a series of nitroolefin acrylates and aldehydes. The N‐hydroxyphenylamine component used in the second step has also been varied. The stereochemistry of one product has been verified by an X‐ray crystal structure determination. The water used in the strategy not only constitutes an environmentally benign solvent, but also helps to improve the reactivity and stereoselectivity.     

A Convenient Synthesis of 1,2,4‐ and 1,3,4‐Azadiphospholes

A new synthetic route to functionalized neutral and anionic azadiphospholes from easily accessible starting materials is described. Equimolar reaction of Na(OCP) and N‐(2,6‐dimethylphenyl)pivalimidoyl chloride 2 a cleanly affords the imidoxy‐functionalized 1,2,4‐azadiphosphole 3 a . Using Na(OCP) and imidoyl chloride in a 2:1 ratio leads to an anionic four‐membered ring Na[ 4 a ], which has been structurally characterized. During 16 h at room temperature, Na[ 4 a ] rearranges to the anionic 1,3,4‐azadiphospholide Na[ 5 a ] with release of carbon monoxide. Applying the more sterically demanding N‐(2,6‐diisopropylphenyl)pivalimidoyl chloride allows isolation of the 1,3,4‐azadiphospholide Na[ 5 b ] in good yield (>70 %). Possible mechanisms leading to the new isomeric azadiphospholides have been investigated with the aid of high‐level composite calculations.     

Stereoselective Nickel‐Catalyzed [2+2] Cycloadditions of Ene‐Allenes

A stereoselective nickel‐catalyzed [2+2] cycloaddition of ene‐allenes is reported. This transformation encompasses a broad range of ene‐allene substrates, thus providing efficient access to fused cyclobutanes from easily accessed π‐components. A simple and inexpensive first‐row catalytic system comprised of [Ni(cod)₂] and dppf was used in this process, thus constituting an attractive approach to synthetically challenging cyclobutane frameworks under mild reaction conditions.     

Metal‐Free Synthesis of Functional 1‐Substituted‐1,2,3‐Triazoles from Ethenesulfonyl Fluoride and Organic Azides

The boom in growth of 1,4‐disubstituted triazole products, in particular, since the early 2000’s, can be largely attributed to the birth of click chemistry and the discovery of the Cu^I‐catalyzed azide–alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1‐substituted‐1,2,3‐triazoles has been surprisingly more challenging. Reported here is a straightforward and scalable click‐inspired protocol for the synthesis of 1‐substituted‐1,2,3‐triazoles from organic azides and the bench stable acetylene surrogate ethenesulfonyl fluoride (ESF). The new transformation tolerates a wide selection of substrates and proceeds smoothly under metal‐free conditions to give the products in excellent yield. Under controlled acidic conditions, the 1‐substituted‐1,2,3‐triazole products undergo a Michael addition reaction with a second equivalent of ESF to give the unprecedented 1‐substituted triazolium sulfonyl fluoride salts.     

Syntheses of High‐Valent fac‐[99mTcO3]+ Complexes and [3+2] Cycloadditions with Alkenes in Water as a Direct Labelling Strategy

Reported herein is a new concept for the labelling of biomolecules with small [^{99 m}TcO₃]⁺ complexes through a [3+2] cycloaddition with alkenes for radiopharmaceutical applications. We developed convenient reactions for the synthesis of small, water stable fac‐[TcO₃(tacn‐R)]⁺ complexes (⁹⁹Tc and ^99mTc, tacn=1,4,7‐triazacyclononane, R=H, ‐CH₂‐C₆H₅, ‐CH₂‐C₆H₄COOH). With alkenes, these high valent [^99mTcO₃]⁺ complexes undergo [3+2] cycloaddition with formation of the corresponding Tc^V–glycolato complexes. The ^99mTc^V and ^99mTc^VII complexes are stable at 37 °C in water and in the presence of serum proteins. Therefore, new opportunities in technetium chemistry are enabled with a high potential for medicinal and biological applications. In contrast to classical labelling, the presented strategy is ligand and not metal‐centred.     

The Divergent Synthesis of Nitrogen Heterocycles by Rhodium(II)‐Catalyzed Cycloadditions of 1‐Sulfonyl 1,2,3‐Triazoles with 1,3‐Dienes

The first rhodium(II)‐catalyzed aza‐[4+3] cycloadditions of 1‐sulfonyl 1,2,3‐triazoles with 1,3‐dienes have been developed, and enable the efficient synthesis of highly functionalized 2,5‐dihydroazepines from readily available precursors. In some cases, the reaction pathway could divert to formal aza‐[3+2] cycloadditions, thus leading to 2,3‐dihydropyrroles. In this context, the titled reaction represents a capable tool for the divergent synthesis of two types of synthetically valuable aza‐heterocycles from common rhodium(II) iminocarbene intermediates.     

One‐Pot Stereoselective Synthesis of 2‐Acylaziridines and 2‐Acylpyrrolidines from N‐(Propargylic)hydroxylamines

The stereoselective direct transformation of N‐(propargylic)hydroxylamines into cis‐2‐acylaziridines was achieved by the combined use of AgBF₄ and CuCl. Copper salts were found to promote the transformation of the intermediary 4‐isoxazolines into 2‐acylaziridines and both 3‐aryl‐ and 3‐alkyl‐substituted 2‐acylaziridines could be prepared by using this method. Furthermore, subsequent 1,3‐dipolar cycloaddition of azomethine ylides that were generated in situ from the intermediary 2‐acylaziridines with maleimides was achieved in a stereoselective one‐pot procedure to afford the corresponding 2‐acylpyrrolidines, which consisted of an octahydropyrrolo[3,4‐c]pyrrole skeleton.     

Enantioselective Formal [4+2] Cycloadditions to 3‐Nitroindoles by Trienamine Catalysis: Synthesis of Chiral Dihydrocarbazoles

The first enantioselective formal [4+2] cycloadditions of 3‐nitroindoles are presented. By using 3‐nitroindoles in combination with an organocatalyst, chiral dihydrocarbazole scaffolds are formed in moderate to good yields (up to 87 %) and enantioselectivities (up to 97 % ee). The reaction was extended to include enantioselective [4+2] cycloadditions of 3‐nitrobenzothiophene. The reaction proceeds through a [4+2] cycloaddition/elimination cascade under mild reaction conditions. Furthermore, a diastereoselective reduction of an enantioenriched cycloadduct is presented. The mechanism of the reaction is discussed based on experimental and computational studies.     

A Versatile Iron‐Catalyzed Protocol for the One‐Pot Synthesis of Isoxazoles or Isoxazolines from the Same Propargylic Alcohols

The use N‐sulfonyl‐protected hydroxylamines as bi‐nucleophiles in iron‐catalyzed propargylic substitutions allows the selective one‐pot synthesis of four classes of substituted isoxazoles or isoxazolines from the same propargylic alcohols (21 examples) by simply tuning the nature of the base. By using an iron(III) catalyst and a base such as triethylamine (3 equiv), isoxazoles 3 are obtained in good isolated yields (56–95%), whereas N‐sulfonyl‐protected isoxazolines 6 are selectively obtained (77–93% yield) by using iron and gold catalysts in the presence of a catalytic amount of pyridine (10 mol%).