Non‐Diazo C−H Insertion Approach to Cyclobutanones through Oxidative Gold Catalysis

Abstract

Cyclobutanones are synthetically versatile compounds that often require extensive effort to access. Herein, we report a facile synthesis of cyclobutanones based on the C(sp3)−H insertion chemistry of oxidatively generated gold carbenes. Various cyclobutanones were obtained in synthetically useful yields from substrates with minimal structural prefunctionalization. This discovery reveals new synthetic utilities of gold‐catalyzed oxidative transformations of alkynones.

Homogeneous Gold-Catalyzed Oxidation Reactions

“…L. Zhang later optimized the C(sp 3 )−H insertion chemistry toward the selective formation of cyclobutanones. 139 A bulky phosphine ligand such as BrettPhos or t BuBrettPhos is essential for the desired regioselectivity, which is supported by DFT studies. One common feature of these cases is the presence of a quaternary carbon center in the substrate backbone in order to harness the rate-enhancing Thorpe−Ingold effect.…”

“…In addition to the monocyclic cyclopentanone products, spiro, fused, and bridged bicyclic cyclopentanones were formed in good yields. L. Zhang later optimized the C­(sp 3 )–H insertion chemistry toward the selective formation of cyclobutanones . A bulky phosphine ligand such as BrettPhos or t BuBrettPhos is essential for the desired regioselectivity, which is supported by DFT studies.…”

Gold-Catalyzed Synthesis of Small Rings

“…The group of Zhang developed methods for the selective formation of cyclobutanones 786 and cyclopentanones 787 depending on the ligand and substrate structures through the intramolecular insertion into C­(sp 3 )–H bonds by oxidatively generated β-diketone-α-gold carbenes 788 (Scheme ). , …”

Gold(I)-Catalyzed Oxidative Amination of β-Amino-ynones to Quaternary Ammonium-olate Salts: The Benefit of a P,N-Bidentate Ligand

“…Ynone, as a polarized alkyne, is also studied, and the α-oxo gold carbene/carbenoid generated in situ is trapped by relative nucleophiles, such as oxygen, the aryl group, and CC and CC bonds (Scheme A). Despite some examples of gold oxidation of ynones to form C–C and C–O bonds, the process in which gold carbene generated in situ engages in selective C–N bond formation with a soft nitrogen atom will remain challenging for the following reasons. (I) The nitrogen atom without being protected by an electron deficient group can coordinate with the gold catalyst, which might decrease the reaction rate or prevent the reaction by decreasing the gold catalyst activity.…”