Site-Selective Acceptorless Dehydrogenation of Aliphatics Enabled by Organophotoredox/Cobalt Dual Catalysis

Abstract

The value of catalytic dehydrogenation of aliphatics (CDA) in organic synthesis has remained largely underexplored. Known homogeneous CDA systems often require the use of sacrificial hydrogen acceptors (or oxidants), precious metal catalysts, and harsh reaction conditions, thus limiting most existing methods to dehydrogenation of non-or low-functionalized alkanes. Here we describe a visible-light-driven, dual-catalyst system consisting of inexpensive organophotoredox and base-metal catalysts for roomtemperature, acceptorless-CDA (Al-CDA). Initiated by photoexited 2-chloroanthraquinone, the process involves H atom transfer (HAT) of aliphatics to form alkyl radicals, which then react with cobaloxime to produce olefins and H 2 . This operationally simple method enables direct dehydrogenation of readily available chemical feedstocks to diversely functionalized olefins. For example, we demonstrate, for the first time, the oxidant-free desaturation of thioethers and amides to alkenyl sulfides and enamides, respectively. Moreover, the system's exceptional site selectivity and functional group tolerance are illustrated by late-stage dehydrogenation and synthesis of 14 biologically relevant molecules and pharmaceutical ingredients. Mechanistic studies have revealed a dual HAT process and provided insights into the origin of reactivity and site selectivity.

Selective dehydrogenation of small and large molecules by a chloroiridium catalyst

“…With L6 /[Ir(COD)Cl] 2 , the dehydrogenation occurred exclusively at the latter to form 5ar . Such a site selectivity is complementary to that obtained by the photochemical dehydrogenation involving a hydrogen atom transfer mechanism ( 26 ), wherein the dehydrogenation occurred preferentially at the 1,2-DSE bearing the electron-rich C─H bonds adjacent to the N atoms (see fig. S30 for the comparative experiment).…”

“…1B]. While directed dehydrogenation of 1,1-DSE using existing directing groups or pendant radical precursors (20)(21)(22)(23) and dehydrogenation of activated 1,1-DSE (24)(25)(26) have been reported, methods of undirected dehydrogenation of unactivated 1,1-DSE have remained underexplored. In this work, we present the first examples of site-selective catalytic desaturation of unactivated 1,1-DSE to form 1,1-disubstituted ethylene without the need for a directing group.…”

Phenanthrenequinone (PQ) catalyzed cross-dehydrogenative coupling of alkanes with quinoxalin-2(1H)-ones and simple N-heteroarenes under visible light irradiation

“…Based on our observations and related reports, 16,17 e a proposed mechanism of the C3-alkylation reaction is depicted in Scheme 8 using 1-methylquinoxalin-2(1 H )-one ( 1a ) and cyclohexane ( 2a ) as the model substrates. First, PQ was excited to its excited state PQ* under blue LED irradiation.…”

“…14 Organic photoredox catalysis in combination with aerobic oxidation using oxygen as the sole oxidant provides environmentally benign and efficient synthesis procedures, 15 which can effectively avoid high temperatures and stoichiometric oxidants. Among the organic photoredox catalysts, quinones could also act as effective and versatile photocatalysts for hydrogen atom transfer, 16 and to the best of our knowledge, visible-light-induced phenanthrenequinone (PQ) catalyzed direct functionalization of alkanes has rarely been reported. In continuation of our interest in green chemistry and C(sp 3 )–H functionalization, 17 and inspired by the reported results, we wish to report herein an efficient and mild protocol for the synthesis of 3-alkylquinoxalin-2(1 H )-ones and other alkyl N-heteroarenes via a photocatalyzed alkylation of quinoxalin-2(1 H )-ones and other N-heterocycles with simple alkanes under visible light irradiation using phenanthrenequinone (PQ) as a photocatalyst.…”

Dual Photoredox and Cobalt Catalysis Enabled Transformations

“…Recently, a novel dual catalytic strategy for the synthesis of alkenes directly from aliphatic compounds was achieved by Huang group via dehydrogenation without any sacrificial hydrogen acceptors (or oxidants). [27] Series of diversely functionalized alkanes were used along with photocatalyst (2-chloroquinone) and cobaloxime (from Co(OAc) 2 • 4H 2 O and dmgH 2 ) for the dual catalytic system (Scheme 12). This dual catalytic method shows a broad substrate scope and good functional group compatibility.…”