Catalytic Access to α-Oxo Gold Carbenes by N–O Bond Oxidants

Abstract

Metal carbenes are highly versatile species that mediate various transformations. Recent advances in gold catalysis have allowed catalytic access to α-oxo metal carbenes from the alkyne functionality. Compared with traditional methods that rely upon metal-catalyzed decomposition of diazo precursors, the generation of this synthon occurs in an environmentally more appealing fashion by gold-catalyzed alkyne oxygenation. Hydroxylamine derivatives are typically prepared from hydroxylamine salts that are cheap and can be handled without special precaution. In reactions with an alkyne activated by gold, relatively stable nitrones and related reagents undergo efficient O-atom transfer to form putative α-oxo gold carbenes. The highly reactive nature of these species could be utilized in a variety of cascade transformations. Herein, recent synthetic methods based on this reactivity as well as the currently available mechanistic and structural studies through computational and experimental methods have been discussed. A variety of tandem reactions performed by our laboratory and others have demonstrated the synthetic utility of catalytically generated α-oxo gold carbenes and enabled access to various heterocycles. For example, a reaction between nitrones and alkynes led to azomethine ylides for the [3 + 2] dipolar cycloaddition. Alternatively, α-oxo gold carbenes can be transformed into enolate equivalents through a 1,2-pinacol shift. The addition of hydroxylamine derivatives across triple bonds led to oxoamination, providing α-aminocarbonyl compounds or regioselective Fisher indole-type synthesis. N-O bond cleaving redox chemistry paved the way for intermolecular redox processes, most notably by use of pyridine-N-oxide derivatives with expanding synthetic applications. In closing, other metal-based oxygenations using N-O bond oxidants will be highlighted. One particularly interesting aspect is the process leading to metal vinylidene complexes. Trapping of this intermediate resulted in opposite regioselectivity from gold catalysis in alkyne oxygenation and led to ketene intermediates for use in subsequent cascade transformations.

Ring Expansion and 1,2‐Migration Cascade of Benzisoxazoles with Ynamides: Experimental and Theoretical Studies

“…The Au-catalyzed Noxide assisted alkyne oxidation and cycloisomerization of 1,nenynes are particularly notable gold-carbene-based transformations. [2, 3] In addition, the nucleophilic nitrenoid equivalents, for example, azides, [4] pyridium ylides, [5] 2H-azirines, [6] and others [7] have been used in the generationo fg old carbene species. The formation of Au-carbenes from ynamides occurs via the elimination of ac ounter ion or al eaving group after electron back donation of gold (Scheme 1a).…”

Brønsted Acid Catalyzed Oxygenative Bimolecular Friedel–Crafts‐type Coupling of Ynamides

“…(1)].I ndeed, the reaction of ynamides 1a with enantio-enriched (S)-2g (200 mol %) in the presence of HNTf 2 catalyst led to isolation of 3a in excellent yield (94 %) and good enantioselectivity (83 %ee), providing ad irect proof that concerted S N 2' pathway is operative. (1)]. [18] We quickly applied this test to typical Au [5a] and Zncatalyzed conditions, [5c] again leading to asignificant enantioinduction in both cases [66-82 % ee,E q.…”

Enantioselective Aza‐Ene‐type Reactions of Enamides with Gold Carbenes Generated from α‐Diazoesters

“…[10b,11] Regardless of which resonance form is the predominant one,the carbon atom bound to gold is electron-deficient, and the gold carbene shows electrophilicity akin to Fischer carbenes. [10][11][12] Enamides are active nucleophiles that are also capable of participating in aza-ene reactions with imines. [10][11][12] Enamides are active nucleophiles that are also capable of participating in aza-ene reactions with imines.…”

“…In the presence of 10 mol %o fL1AuNTf 2 ,avariety of chiral phosphoric acids [17] were surveyed in the reaction of diazoacetate 1a and enamide 2a (Table 1, entries 1-4). Surprisingly,l owering the amount of chiral phosphoric acid 5d led to as ignificant improvement in the enantioselectivity while the yield was maintained (entries [12][13][14][15]. As olvent screen showed that the use of methyl tert-butyl ether (MTBE) enhanced the enantioselectivity of this process (entry 5; see also the Supporting Information, Table S1).…”