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Direct olefinic C-H functionalization represents the ideal way of introducing an alkenyl group into organic molecules. A well-known process is the Heck reaction, which involves alkene insertion and β-hydride elimination in the presence of a transition metal. However, the traditional Heck reaction mainly deals with the alkenylation of aryl or vinyl electrophiles. Recent developments have revealed that alkenylation can also be achieved through radical addition to alkenes and following single-electron-transfer (SET) oxidation/elimination. The radical alkenylation pathway allows alkenylation with a variety of carbon-centered radicals and even heteroatom-centered radicals. This tutorial review gives an overview of recent advances in this emerging field.

CONSPECTUS: Oxidative cross-coupling reactions between two nucleophiles are a powerful synthetic strategy to synthesize various kinds of functional molecules. Along with the development of transition-metal-catalyzed oxidative cross-coupling reactions, chemists are applying more and more first-row transition metal salts (Fe, Co, etc.) as catalysts. Since first-row transition metals often can go through multiple chemical valence changes, those oxidative cross-couplings can involve single electron transfer processes. In the meantime, chemists have developed diverse mechanistic hypotheses of these types of reactions. However, none of these hypotheses have led to conclusive reaction pathways until now. From studying both our own work and that of others in this field, we believe that radical oxidative cross-coupling reactions can be classified into four models based on the final bond formations. In this Account, we categorize and summarize these models. In model I, one of the starting nucleophiles initially loses one electron to generate its corresponding radical under oxidative conditions. Then, bond formations between this radical and another nucleophile create a new radical, [Nu(1)-Nu(2)](•), followed by a further radical oxidation step to generate the cross-coupling product. The radical oxidative alkenylation with olefin, radical oxidative arylative-annulation, and radical oxidative amidation are examples of this model. In model II, one of the starting nucleophiles loses its two electrons via two steps of single-electron-transfer to generate an electrophilic intermediate, followed by a direct bond formation with the other nucleophile. For example, the oxidative C-O coupling of benzylic sp(3) C-H bonds with carboxylic acids and oxidative C-N coupling of aldehydes with amides are members of this model group. For model III, both nucleophiles are oxidized to their corresponding radicals. Then, the radicals combine to form the final coupling product. The dioxygen-involved radical oxidative cross-couplings between sulfinic acids and olefins or alkynes belong to this bond formation model. Lastly, in model IV, one nucleophile loses two electrons to generate an electrophilic intermediate, while the other nucleophile loses one electron to generate a radical. Then, a bond forms between the cation and the radical to generate a cationic radical, followed by a one-electron reduction to afford the final coupling product. The oxidative coupling between arylboronic acids and simple ethers was classified in this model. At the current stage, there are only a few examples presented for models III and IV, but they represent two types of potentially important transformations. More and more examples of these two models will be developed in the future.

A deoxygenative gem-diborylation and gem-silylborylation of aldehydes and ketones is described. The key for the success of this transformation is the base-promoted C-O bond borylation or silylation of the generated α-oxyboronates. Experimental and theoretical studies exhibit that the C-O bond functionalization proceeds via an intramolecular five-membered transition-state (9-ts) boryl migration followed by a 1,2-metalate rearrangement with OBpin as a leaving group. The transformation occurs with an inversion on the carbon center. Direct conversion of aldehydes and ketones to gem-diboron compounds was achieved by combining copper catalysis with this base-promoted C-OBpin borylation. Various aldehydes and ketones were deoxygenatively gem-diborylated. gem-Silylborylation of aldehydes and ketones were achieved by a stepwise operation, in which Bpin initially react with those carbonyls followed by a silylation with Bpin-SiMePh.

CHoose nickel: The nickel‐catalyzed oxidative arylation of C(sp3)H bonds has been achieved. Several substituted arylboronic acids and various C(sp3)H bonds were found to be suitable substrates for this novel transformation, which is likely to proceed through a radical pathway. This method allows the introduction of simple ether derivatives to construct α‐arylated ethers. FG=functional group.

Let's get radical: The first copper‐catalyzed oxidative coupling of alkenes and aldehydes was developed. Various aldehydes were utilized as substrates to construct α,β‐unsaturated ketones. A preliminary mechanistic study indicated that this reaction is likely to proceed through a single‐electron transfer.

One step from alcohol to ester: A palladium‐catalyzed oxidative esterification of various benzylic alcohols with methanol and long‐chain aliphatic alcohols was carried out in the presence of molecular oxygen as the oxidant (see scheme). By considering the effects of substitution and potential mechanistic pathways, the applicability of this method to a range of different substrates was shown.

A copper-catalysed direct oxidative Csp(3)-H methylenation to terminal olefins using DMF as one carbon source was developed. In this reaction, various functional groups were well tolerated, thus providing a simple way to construct arylvinylketones and arylvinylpyridines. The preliminary mechanistic investigations revealed that CH2 was from DMF (N-CH3).