A nickel's worth of transferred energy

Traditional organic photochemistry often relies on sensitizers, molecules that efficiently absorb light and then transfer the energy to other compounds to spur reactivity. Welin et al. leveraged this approach to stimulate an organometallic nickel catalyst. They photoexcited an iridium complex with blue light. The ensuing energy transfer to nickel enabled C–O bond formation, coupling aryl halides with carboxylic acids. A similar approach could generate a variety of additional reactivity patterns through photosensitized transition metal catalysis.

Science, this issue p. 380

A light approach to C-N bond formation

The need to form C-N bonds arises frequently in drug discovery research. One versatile approach involves the attachment of the C and N fragments to a Pd catalyst. This approach needs a bulky ligand to “crowd” the fragments together off the metal center. Corcoran et al. present a complementary approach that uses Ni in place of Pd. Instead of the bulky ligand, they used a light-activated cocatalyst that strips an electron from the Ni to accelerate the bond formation. A screen involving elaborately substituted reagents confirmed the utility of this approach in cases that challenge the traditional Pd coupling.

Science, this issue p. 279

A tip of the HAT to C-C bond formation

Iridium and nickel are already a proven team for forging carbon-carbon bonds. The iridium harvests blue light from a simple light-emitting diode and orchestrates the coupling by the nickel. Shaw et al. now add a third player to the team, a hydrogen atom transfer (HAT) catalyst (see the Perspective by Fruit). Together, the trio of catalysts can link bromo- or chloroaryl rings directly to C-H sites adjacent to nitrogen or oxygen, with no need for prior modification. The reaction is highly selective across a broad range of substrates.

Science, this issue p. 1304; see also p. 1277

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A trio helps activate C-H bonds in alcohols

Enzymes can accelerate chemical reactions by activating specific portions of a molecule through well-placed H bonds. Jeffrey et al. showcase the power of H-bonding in a synthetic context. Here, reactivity at the C centers of alcohols is selectively induced by using an H-bonding catalyst to bind the hydroxyl group of the alcohol. The adjacent C-H bonds now become susceptible to a reaction accelerated by another pair of catalysts. In combination, the trio of catalysts promotes C-C bond formation at the alcohol C within an array of competing sites.

Science, this issue p. 1532

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A bright outlook for carbon coupling

In contemporary organic chemistry, it is straightforward to forge bonds between unsaturated carbons (i.e., carbons already engaged in double bonds) using cross-coupling catalysis. The protocol runs into some trouble, however, if one or both starting carbon centers are saturated (purely single-bonded). Tellis et al. and Zuo et al. independently found that combining a second, light-activated catalyst with a nickel cross-coupling catalyst could achieve selective coupling of saturated and unsaturated reagents (see the Perspective by Lloyd-Jones and Ball). Their methods rely on single-electron transfer from the light-activated catalyst to the saturated carbon, thereby enhancing its reactivity more effectively than the twoelectron mechanisms prevailing in traditional protocols.

Science, this issue p. 433, p. 437; see also p. 381

Beta Bonding

Carbonyl compounds, which incorporate carbon-oxygen double bonds, are among the most productively reactive molecules in synthetic as well as biochemical contexts. The carbon directly bonded to oxygen is rendered highly electrophilic, while the adjacent (α) carbons are easily deprotonated to undergo further transformations. In contrast, the β carbons that are one step further along the chain tend to be relatively inert. Pirnot et al. (p. 1593) now show that a dual catalyst system—consisting of an amine and a photoactive metal complex—can activate the β carbons of carbonyl compounds to couple with aryl substrates.

An unanticipated photocatalytic carbon-carbon bond-forming reaction emerged from screening many unusual reagent combinations.

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Photoredox catalysis and organocatalysis represent two powerful fields of molecule activation that have found widespread application in the areas of inorganic and organic chemistry, respectively. We merged these two catalysis fields to solve problems in asymmetric chemical synthesis. Specifically, the enantioselective intermolecular α-alkylation of aldehydes has been accomplished using an interwoven activation pathway that combines both the photoredox catalyst Ru(bpy)₃Cl₂ (where bpy is 2,2′-bipyridine) and an imidazolidinone organocatalyst. This broadly applicable, yet previously elusive, alkylation reaction is now highly enantioselective and operationally trivial.

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The asymmetric α-addition of relatively nonpolar hydrocarbon substrates, such as allyl and aryl groups, to aldehydes and ketones remains a largely unsolved problem in organic synthesis, despite the wide potential utility of direct routes to such products. We reasoned that well-established chiral amine catalysis, which activates aldehydes toward electrophile addition by enamine formation, could be expanded to this important reaction class by applying a single-electron oxidant to create a transient radical species from the enamine. We demonstrated the concept of singly occupied molecular orbital (SOMO) activation with a highly selective α-allylation of aldehydes, and we here present preliminary results for enantioselective heteroarylations and cyclization/halogenation cascades.