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Benzaldehyde photoredox heteroarylates amides and ethers

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Household CFL light plus benzaldehyde and APS couples heteroarene C–H bonds to amide/ether α-C–H positions without a metal photocatalyst.

Source

Direct α-heteroarylation of amides (α to nitrogen) and ethers through a benzaldehyde-mediated photoredox reaction

Zhang Y, Teuscher KB, Ji H · Chemical science · 2016

doi.org/10.1039/c5sc03640bRead the full paper ↗46 citationscc by

What they did

Authors developed a cross-dehydrogenative coupling using benzaldehyde as a photoabsorber, ammonium persulfate as oxidant, and CFL/black-light irradiation, mapping scope on benzothiazoles/quinolines/amides/ethers and probing mechanism with filters, TEMPO, and substituted benzaldehydes.

What they found

Near-UV (≈364 nm) from CFLs drives the reaction; 0.5 equiv benzaldehyde can suffice (90%); gram-scale 85% isolated yield; formamide carbonyl C–H and N-alkyl C–H both react (e.g. 88% with 8:1 carbonyl selectivity for N-methylformamide).

The limits

What it doesn't show

Partners must be used in large excess, and the method is not a catalytic closed photoredox cycle with a recylable Ir/Ru dye.

Key terms

CDC
Cross-dehydrogenative coupling joining two C–H positions with an oxidant.
Photoredox
Light-driven single-electron transfer that generates radicals under mild conditions.
APS
Ammonium persulfate, the stoichiometric oxidant whose decomposition is enhanced by amides and photoexcited benzaldehyde.
CFL
Compact fluorescent lamp used as a household visible/near-UV source.
α-heteroarylation
Attachment of a heteroarene to the carbon adjacent to N or O.

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The light-absorbing mediator is:

Common questions

Is a metal photocatalyst required?

No—the reaction is metal-free with benzaldehyde as mediator.

What light is essential?

Near-UV from the CFL (~364 nm); darkness gives no reaction.

Gram-scale yield?

85% isolated.

What does TEMPO do?

Inhibits the reaction, supporting radicals.

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