Kupferkatalysierte aerobe oxidative C‐H‐Funktionalisierungen: Trends und Erkenntnisse zum Mechanismus

Abstract

Die selektive Oxidation von C‐H‐Bindungen und der Einsatz von O2 als stöchiometrisches Oxidationsmittel stellen zwei wesentliche Herausforderungen in der organischen Chemie dar. Kupfer(II) ist ein vielseitiges Oxidationsmittel für verschiedene oxidative Kupplungen, die durch Einelektronen‐Transfer (SET) von elektronenreichen organischen Molekülen ausgelöst werden. Viele dieser Reaktionen können mit Kupfer katalytisch durchgeführt werden, wenn molekularer Sauerstoff als Oxidationsmittel eingesetzt wird, um den aktiven Kupfer(II)‐Katalysator zu regenerieren. Daneben wurden auch zahlreiche neue Cu‐katalysierte C‐H‐Oxidationen mit elektronenarmen Substraten beschrieben, von denen ein SET zum Kupfer(II) unwahrscheinlich scheint. In einigen dieser Fälle konnte die Beteiligung von Organokupfer(III)‐Intermediaten im Reaktionsmechanismus nachgewiesen werden. Metallorganische C‐H‐Oxidationen dieser Art eröffnen neue bedeutende Möglichkeiten für das Gebiet der Cu‐katalysierten aeroben Oxidationen.

Copper‐Catalyzed Site‐Selective Intramolecular Amidation of Unactivated C(sp3)H Bonds

“…[6] Very recently, nickel-catalyzed site-selective alkylation of unactivated sp 3 CÀH bonds was established in our laboratory. [9] It should also be mentioned that although copper-catalyzed coupling reactions through an sp 2 or sp 3 CÀH activation process have been extensively studied, [10] there are only few examples involving direct functionalization of unactivated sp 3 -carbon atoms. [4h,i,p, 8] This novel method provides a complementary approach to access mono-, spiro-, and bicyclic b-lactam derivatives, which are important structural units in biologically active natural products and medicines.…”

Alkenyl and Aryl Peroxides

“…[81,82] Af ew selected cases will be discussed in more detail. The first deserves some attention because of its significance for the development of chemistry at its time, contributingt ot he fields of oxidative coupling reactions [83] and free radical chemistry.…”

Room‐Temperature Copper‐Catalyzed Oxidation of Electron‐Deficient Arenes and Heteroarenes Using Air

“…Although transition-metal-catalyzed direct functionalization of C À H bonds has emerged as a powerful method to construct new CÀC and CÀheteroatom bonds, [1] oxidative functionalization of CÀH bonds under mild conditions (at room temperature and using air as the oxidant) still remains a very challenging field. [2] In particular, the synthesis of phenols by direct oxidation of arenes with O 2 as the oxidant is still regarded as one of the main challenges for catalysis, and is rarely reported. [3] A groundbreaking method reported by Fujiwara and co-workers used Pd(OAc) 2 as the catalyst to convert benzene into phenol with molecular oxygen; however, this method gave low yields (2-3 %) and used extremely forcing reaction conditions (15 atm O 2 , 15 atm CO, 180 8C).…”

“…[2] In particular, the synthesis of phenols by direct oxidation of arenes with O 2 as the oxidant is still regarded as one of the main challenges for catalysis, and is rarely reported. [3] A groundbreaking method reported by Fujiwara and co-workers used Pd(OAc) 2 as the catalyst to convert benzene into phenol with molecular oxygen; however, this method gave low yields (2-3 %) and used extremely forcing reaction conditions (15 atm O 2 , 15 atm CO, 180 8C). [4] Recently, Yu and Zhang reported a novel Pd-catalyzed direct ortho hydroxylation of potassium benzoates in the presence of O 2 (1 atm) as the oxidant.…”

“…[4] Recently, Yu and Zhang reported a novel Pd-catalyzed direct ortho hydroxylation of potassium benzoates in the presence of O 2 (1 atm) as the oxidant. [5] However, several drawbacks still remain including the high catalyst loading (10 mol % of Pd(OAc) 2 ) and high temperature (115 8C). Thus, it is still necessary to develop a powerful synthetic method for the oxidative hydroxylation of C À H bonds under mild reaction conditions.…”