Catalytic Aerobic Cross-Dehydrogenative Coupling of Azlactones en Route to α,α-Disubstituted α-Amino Acids

Abstract

We developed a catalytic aerobic method to synthesize α,α-disubstituted α-amino acids through cross-dehydrogenative coupling of azlactones. Combining an iron catalyst with a bisoxazolidine ligand resulted in high catalytic performance, and cross-coupling with an indole proceeded smoothly under aerobic conditions. A wide variety of α-aryl and aliphatic amino acid derived azlactones were applied to the present catalysis. In addition, a quaternary carbon could be constructed using oxindole and benzofuranone under aerobic conditions.

Improved Method for Preparation of 3-(1H-Indol-3-yl)benzofuran-2(3H)-ones

“…Since both indole and benzo–furanone structural fragments are omnipresent in nature and listed as privileged scaffolds for drug discovery, chimeric indigo-, or isoindigo-like molecules possessing both these moieties also attracted certain attention. There are several reports describing the preparation of these unique compounds and studies of their applications in medicinal chemistry and material sciences [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. A common theme described in these reports is the metal-catalyzed C-C bond-forming reactions to accomplish the coupling between the indole and benzofuranone building blocks [ 1 , 5 , 8 , 10 ].…”

“…There are several reports describing the preparation of these unique compounds and studies of their applications in medicinal chemistry and material sciences [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. A common theme described in these reports is the metal-catalyzed C-C bond-forming reactions to accomplish the coupling between the indole and benzofuranone building blocks [ 1 , 5 , 8 , 10 ]. Other approaches used a Lewis acid-mediated reaction of indole derivatives with properly functionalized aromatic precursors (typically phenols or quinones) to furnish a five-membered lactone cycle in benzofurane [ 2 , 6 , 7 ].…”

Copper Catalyzed Oxidative Arylation of Tertiary Carbon Centers

“…8 More recently, the Kambe group reported a copper-catalyzed coupling between 3-aryl benzofuran-2-ones and heteroarenes 9 (Scheme 1c), and the Ohshima group reported an iron-catalyzed coupling between azlactones and heteroarenes. 10 The nonoxidative arylation of aryl malononitriles has only been reported using diaryliodonium salts but was limited due to the nature of the iodonium species (Scheme 1d). 11 Overall, the oxidative coupling of these species with phenols and anilines has not been documented and is the focus of this report (Scheme 1e).…”

Visible-Light-Induced Tertiary C(sp3)–H Sulfonylation: An Approach to Tertiary Sulfones

“…To account for observed reactivities coupled to the above investigations and based on literature precedents, − a plausible mechanistic network is outlined in Scheme . First, azomethine ylide A is generated by the condensation of 5-chloroindoline-2,3-diones 1c with 4-hydroxyproline 2 , followed by decarboxylation, which is facilitated in the presence of I 2 /blue LED. , Spontaneously, dehydration leads to azomethine ylide B , and the more stable zwitterion intermediate C is formed by 1,5 proton transfer and will change to intermediate 5c . , Next, the sequential addition of p -toluenesulfinic acid and 2 mol % Na 2 -Eosin Y is accomplished.…”

“…Furthermore, the generated sulfonyl radical cation D is deprotonated by O 2 •– and converted into the oxygen-centered sulfonyl radical E , followed by resonance and transformation into the sulfur-centered radical F . Under the irradiation of I 2 /blue LED, intermediate 5c is converted into 5-chloro-3-(1 H -pyrrol-1-yl)­indolin-2-one radical G via homolysis of the corresponding homocoupling dimer 5c ′, formed by the transient homocoupling dimer strategy under the oxidative conditions. ,− This radical G couples to the sulfur-centered sulfonyl radical F to deliver the expected tertiary sulfone products 4 . Furthermore, the sulfur-centered sulfonyl radical F undergoes self-coupling and generates the intermediate disulfone H .…”