Direct activation of gaseous hydrocarbons remains a major challenge for the chemistry community. Because of the intrinsic inertness of these compounds, harsh reaction conditions are typically required to enable C(sp3)–H bond cleavage, barring potential applications in synthetic organic chemistry. Here, we report a general and mild strategy to activate C(sp3)–H bonds in methane, ethane, propane, and isobutane through hydrogen atom transfer using inexpensive decatungstate as photocatalyst at room temperature. The corresponding carbon-centered radicals can be effectively trapped by a variety of Michael acceptors, leading to the corresponding hydroalkylated adducts in good isolated yields and high selectivity (38 examples).

Integration of a pressure-based variable bed flow reactor into an automated solid-phase peptide synthesizer allowed for monitoring of on-resin aggregation and incomplete amide bond formation in real-time.

Photocatalytic hydrogen atom transfer is a very powerful strategy for the regioselective C(sp 3 )-H functionalization of organic molecules. Herein, we report on the unprecedented combination of decatungstate hydrogen atom transfer photocatalysis with the oxidative radical-polar crossover concept to access the direct net-oxidative C(sp 3 )-H heteroarylation. The present methodology demonstrates a high functional group tolerance (40 examples) and is scalable when using continuous-flow reactor technology. The developed protocol is also amenable to the late-stage functionalization of biologically relevant molecules such as stanozolol, (À)ambroxide, podophyllotoxin, and dideoxyribose.Photocatalytic hydrogen atom transfer (HAT) is witnessing an ever-growing interest from the synthetic community as a versatile strategy for the late-stage functionalization of C(sp 3 )ÀH bonds. [1][2][3] In this activation mode, the excited state of a photocatalyst can be conveniently exploited to cleave C(sp 3 ) À H bonds to obtain carbon-centered radicals. By exploiting inherent electronic and steric properties of the parent molecule and by tuning the reaction conditions, these nucleophilic radicals can be obtained with high regioselectiv-ity, thus obviating the need to use any directing or activating groups (Scheme 1 a).Amongst the different HAT photocatalysts, the decatungstate anion (W; [W 10 O 32 ] 4À ) has proven to be an ideal candidate owing to its unique selectivity, robustness and ease of preparation. [4,5] The excited state of W (W*) can be readily obtained upon exposure to UV-A light (l > 365 nm) and has been used for the activation of C(sp 3 )ÀH bonds within a wide variety of hydrogen donors such as ethers, aldehydes, amides and even alkanes. In most cases, the fleeting radical intermediates were used to forge CÀC, [6] CÀF, [7] and CÀO [8] bonds. In contrast, only a handful of examples demonstrate the formation of C À N bonds. [9] These examples mainly rely on the trapping of the radical with a suitable Michael acceptor, e.g., diisopropyl azodicarboxylate (DIAD), delivering the corresponding hydrazides. Despite its synthetic utility to Scheme 1. a) Photocatalytic hydrogen atom transfer (HAT) enables the conversion of CÀH bonds in complex biologically active molecules. b) Established mechanism for the formation of CÀN bonds via TBADT-mediated HAT. c) Proposed approach to realize the regioselective CÀH bond heteroarylation through combination of decatungstateenabled HAT and Radical-Polar Crossover (RPC).

The late-stage introduction of allyl groups provides an opportunity to synthetic organic chemists for subsequent diversification, furnishing a rapid access to new chemical space. Here, we report the development of...

A strategy for both cross-electrophile coupling and 1,2-dicarbofunctionalization of olefins has been developed. Carbon-centered radicals are generated from alkyl bromides by merging benzophenone hydrogen atom transfer (HAT) photocatalysis and silyl radical-induced halogen atom transfer (XAT) and are subsequently intercepted by a nickel catalyst to forge the targeted C(sp 3 )–C(sp 2 ) and C(sp 3 )–C(sp 3 ) bonds. The mild protocol is fast and scalable using flow technology, displays broad functional group tolerance, and is amenable to a wide variety of medicinally relevant moieties. Mechanistic investigations reveal that the ketone catalyst, upon photoexcitation, is responsible for the direct activation of the silicon-based XAT reagent (HAT-mediated XAT) that furnishes the targeted alkyl radical and is ultimately involved in the turnover of the nickel catalytic cycle.