Generating carbyne equivalents with photoredox catalysis

Abstract

Carbon has the unique ability to bind four atoms and form stable tetravalent structures that are prevalent in nature. The lack of one or two valences leads to a set of species-carbocations, carbanions, radicals and carbenes-that is fundamental to our understanding of chemical reactivity. In contrast, the carbyne-a monovalent carbon with three non-bonded electrons-is a relatively unexplored reactive intermediate; the design of reactions involving a carbyne is limited by challenges associated with controlling its extreme reactivity and the lack of efficient sources. Given the innate ability of carbynes to form three new covalent bonds sequentially, we anticipated that a catalytic method of generating carbynes or related stabilized species would allow what we term an 'assembly point' disconnection approach for the construction of chiral centres. Here we describe a catalytic strategy that generates diazomethyl radicals as direct equivalents of carbyne species using visible-light photoredox catalysis. The ability of these carbyne equivalents to induce site-selective carbon-hydrogen bond cleavage in aromatic rings enables a useful diazomethylation reaction, which underpins sequencing control for the late-stage assembly-point functionalization of medically relevant agents. Our strategy provides an efficient route to libraries of potentially bioactive molecules through the installation of tailored chiral centres at carbon-hydrogen bonds, while complementing current translational late-stage functionalization processes. Furthermore, we exploit the dual radical and carbene character of the generated carbyne equivalent in the direct transformation of abundant chemical feedstocks into valuable chiral molecules.

Recent Synthetic Applications of the Hypervalent Iodine(III) Reagents in Visible-Light-Induced Photoredox Catalysis

“…In 2018, Suero and co-workers developed an aromatic C-H bond diazomethylation reactions using the pseudocyclic hypervalent iodine (I) by ruthenium photoredox catalysis (Wang Z. et al, 2018 ) ( Figure 9 ). The pseudocyclic hypervalent iodine (I) carrying a diazoacetate moiety served as a diazomethyl radical precursor through a SET process in photoredox-catalyzed protocol, and a wide range of aromatic hydrocarbons substituted with alkyl groups, halogens, amides and carbonyls undergo C-H diazomethylation to generate valuable diazo compounds.…”

Blue light-promoted photolysis of aryldiazoacetates

“…In contrast to the numerous protocols reported on thermal processes, photochemical studies with diazocompounds have been performed mostly several decades ago, 9 and modern applications are relatively scarce. 10 , 11 Among these, Suero and co-workers have recently demonstrated that a hypervalent iodine reagent carrying a diazoacetate moiety could be employed in a photoredox-catalyzed protocol for the C–H functionalization of a variety of arenes. 11 b In the sequence, the diazocompounds produced could be further engaged in classical reactions, thus representing an overall formal process to access carbyne equivalents.…”

Regioselective Arene C−H Alkylation Enabled by Organic Photoredox Catalysis

“…Collectively, these directing groups limit the synthetic applicability of metallocarbene C À H alkylation reactions.Recently, Suero and co-workers reported the synthesis of aryl diazoacetate derivatives under photoredox conditions. [10]…”

“…Recently, Suero and co-workers reported the synthesis of aryl diazoacetate derivatives under photoredox conditions. [10]…”