Rapid Access to Functionalized γ-Lactams through Copper-Catalyzed Oxidative Cyclization of Diynes

Abstract

An efficient copper-catalyzed oxidative cyclization of diynes is described. A range of functionalized γ-lactams are readily constructed by utilizing this protocol. This copper-catalyzed oxidative process proceeds through alkyne oxidation, carbene/alkyne metathesis, and donor/donor carbene oxidation sequence. The use of readily available substrates, high flexibility, a simple procedure, and mild reaction conditions render it a viable alternative for the preparation of functionalized γ-lactams.

[Au]-Catalyzed Cyclization of Propargyl-Tethered Ene-Amides: Substrate-Dependent Access to Tetrasubstituted Pyrroles, Aminophenols, and Dihydropyridines

“…These are known compounds. 19 4.1.3. Synthesis of 3-Chloro-2,3-diarylacrylaldehydes (2a−f) and β-Chloro-acrylaldehydes (2g−h).…”

“…16 All reactions, unless stated otherwise, were performed in a dry nitrogen atmosphere. 1 H, 13 C{ 1 H} NMR and 19 F NMR spectra were recorded using 5 mm tubes [field strength: 400 and 100 MHz for 1 H/ 13 C using 400 MHz NMR spectrometer; 500, 125, and 470 MHz for 1 H, 13 C{ 1 H}/ 19 F using 500 MHz NMR spectrometer] in CDCl 3 solution (unless specified otherwise) with shifts referenced to SiMe 4 [=0 for 1 H, 13 C{ 1 H} and CFCl 3 for 19 F]. All J values are in Hz.…”

“…Synthesis of Internal Aryl-Substituted Propynyl-Arylsulfonamides 1j−t: General Procedure (Slightly Modified from That in the Literature). 19 To a suspension of N-(prop-2-yn-1-yl)arylsulfonamide (2.39 mmol, 1.0 equiv), iodobenzene (2.63 mmol, 1.1 equiv), Pd(PPh 3 ) 2 Cl 2 (0.07 mmol, 3 mol %), and CuI (0.09 mmol, 4 mol %) in anhydrous CH 3 CN (7.0 mL), triethylamine (4.78 mmol, 2.0 equiv) was added. The resulting mixture was stirred for 12 h at rt (25 °C).…”

Construction of Spirolactams by Unexpected Oxidative Cyclization of Alkenyl Diynes via Copper Catalysis

“…Over the past several decades, transition metal-catalyzed intermolecular alkyne oxidation by N -oxides has attracted much attention and proven to be a powerful approach for the expeditious assembly of various complex scaffolds. − Importantly, this strategy could effectively avoid the use of hazardous and not easily accessible diazo compounds as precursors for carbene generation. Among these, such oxidative cyclopropanations of enynes have been nicely exploited by Liu, Tang, Li, and others , (Scheme a).…”

“…In particular, asymmetric oxidative cyclopropanations of enynes by employing chiral gold complexes as catalysts were also elegantly demonstrated by Zhang and Zhang . In recent years, transition metal-catalyzed oxidative diyne cyclizations have been well documented to be a powerful method for synthesizing a variety of structurally complex carbocyclic and heterocyclic compounds, as established by Tang, Hashmi, Zhang, and others . Despite these achievements, these reactions have so far been mostly limited to the use of noble metal catalysts such as Au and Rh, and importantly, further functionalizations in these cascade cyclizations occur exclusively at the metal–carbene position.…”