Nucleophilic Nitrenoids Through π‐Acid Catalysis: Providing a Common Basis for Rapid Access into Diverse Nitrogen Heterocycles

Abstract

Nitrogen heterocyclesa re some of the most important and sought-after structuralm otifs in synthetic chemistry.G eneral methods that can be applied towards as tructurally diverse range of different scaffolds are rare. This Focus Reviewd iscusses an emerging area with the field of p-acid catalysis based on the activation of carbon-carbon triple bonds in conjunction with nucleophilicn itrenoids. The resulting approach providesr eady access into a-imino metal carbene reactivity patternst hat can be employed in an umber of quenching processes to realize av ariety of powerful new transformations. The resultingm ethods are characterized by high efficiency,s imple and straightforward reactions et ups, mild conditions, and excellent functional group tolerance. In this Focus Review the different nucleophilic nitrenoid types are explored showing how they can be used across ar ange of (poly)cyclization and formal cycloaddition processes to provide an alternative and directd isconnection pathway in the generation of N-heterocyclic motifs.

Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

“…[1,2] Ynamides,i nc ontrast, are privileged substrates:i np-acid catalysis their donor nature aids metalalkyne coordination and affords highly polarized electrophiles,t hus providing the high chemo-and regioselectivity required for the discovery of efficient intermolecular reactions (Scheme 1a). [3,4] As the resulting inclusion of ad onornitrogen atom limits the utility of the products,r etaining the reactivity profile of these transformations whilst accessing more flexible and readily elaborated substitution patterns would be desirable.T he value of sulfur-substituted compounds [5] coupled with progress in C À Ca nd C-heteroatom bond formation from CÀSbonds, [6] renders alkynyl thioethers appealing alternatives to ynamides.I ndeed the ketenethionium pathway (Scheme 1a)f rom alkynyl thioethers has recently been invoked in proton-catalyzed reactions with nitriles [2g,h] and gold-catalyzed reactions with sulfides.[2i]Ynamides enabled the discovery of formal [3+ +2] dipolar cycloadditions with nucleophilic nitrenoids, [7] thus allowing intermolecular access to a-imino gold carbene-type reactivity for heterocycle synthesis (Scheme 1b). [8, 9] Such reactions, which do not depend on ynamides,a re scarce.…”

“…Ynamides enabled the discovery of formal [3+ +2] dipolar cycloadditions with nucleophilic nitrenoids, [7] thus allowing intermolecular access to a-imino gold carbene-type reactivity for heterocycle synthesis (Scheme 1b). [8, 9] Such reactions, which do not depend on ynamides,a re scarce.…”

“…ities across the S-alkyl and S-aryl series (entries [6][7][8][9][10]. The sulfur substituent is critical, and the internal alkynes 4a/b did not react (entries 11 and 12).…”

The Outer‐Sphere Mechanism of Nitrene Transfer onto Gold(I) Alkyne Complexes

“…This rearrangement is typical in carbenes with α‐hydrogen atoms but is uncommon in gold carbenes. Notable exceptions that have been reported include a study by Gevorgyan on 1,2‐H and 1,2‐Si migrations onto gold carbenes in 2 H ‐furan‐3‐gold carbene intermediates assisted by rearomatization at the furan ring and the 1,2‐H migrations proposed in the gold‐catalyzed intramolecular acetylenic Schmidt reaction . The atomic motion in this step resembles that of a type I dyotropic rearrangement involving both the α‐H and gold atoms.…”

“…Notable exceptionst hat have been reported include as tudy by Gevorgyan on 1,2-H and 1,2-Si migrations onto gold carbenes in 2H-furan-3-gold carbene intermediates assistedb yr earomatization at the furan ring [47] and the 1,2-H migrations proposed in the gold-catalyzed intramolecular acetylenic Schmidt reaction. [30,[48][49][50] The atomic motion in this step resembles that of at ype Idyotropic rearrangement [51] involving both the a-H and gold atoms. In this kind of rearrangement, two concerted 1,2-shifts of substituents attachedt oa djacent carbon atoms occur,s ot hat they exchange their relative positions.…”