Why gold carbenes hit phenol para-C–H
DFT plus deuterium controls show (PhO)3PAu carbenes add at phenol para-C, then two waters shuttle the proton, beating O–H insertion.
Source
Origins of unique gold-catalysed chemo- and site-selective C-H functionalization of phenols with diazo compounds
Study at a glance
- Design
- Computational / modelling — DFT free-energy profiles for gold-carbene phenol functionalization with deuterium-control reactions
- N
- Computed (PhO)3PAu versus Ph3P pathways plus deuterated-phenol controls
- Population
- Gold-carbene C–H versus O–H insertion into phenols
- Outcome
- Para C–H addition plus a two-water proton shuttle outcompetes O–H insertion with (PhO)3PAu carbenes
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Inspect source passages
Why gold carbenes hit phenol para-C–H
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
Au-carbene formation barriers are 6.5 and 11.4 kcal mol–1 for the two ligands
The calculated free energy profiles indicate that the generation of Au-carbene species is quite facile and drastically exothermic, with the low barriers of 6.5 and 11.4 kcal mol –1 , respectively.
Para addition of the gold carbene has a 15.6 kcal mol–1 barrier
In our DFT calculations, a transition state TS-c1 with a barrier of 15.6 kcal mol –1 is located for the addition of the gold carbene at the para -position of phenol.
What they did
They computed free-energy profiles for gold-carbene addition to phenol with (PhO)3P versus Ph3P ligands, compared C–H versus O–H insertion, and tested water-assisted proton transfer against a direct [1,2]-H shift. Control reactions with deuterated phenol supported the water-shuttle pathway.
What they found
Au-carbene formation is cheap (6.5 and 11.4 kcal mol–1). Para addition (15.6 kcal mol–1) beats ortho (19.3) and meta (23.6). Direct [1,2]-H shift is 30.1 kcal mol–1, while a two-water shuttle is favored. The C–H product is 10.8 kcal mol–1 more stable than the O–H insertion product. Switching to Ph3P raises the C–H addition barrier and lowers the O–H barrier.
The limits
What it doesn't show
The computed barriers are IEFPCM solution free energies at 298 K, not measured rates. Only phenol/α-diazoester systems are mapped, so the water-shuttle model is not proven for other arenes or metals. Isolated product yields for a broad substrate table are not the focus.
Key terms
- Gold carbene
- Electrophilic Au=CR2 species formed when a gold catalyst decomposes a diazo compound by losing N2.
- Chemoselectivity
- Which bond reacts: here aromatic C–H insertion versus phenolic O–H insertion.
- Proton shuttle
- Water molecules that relay a proton between sites instead of a concerted intramolecular hydride shift.
- Enol intermediate
- After para addition, a gold-bound enol forms before tautomerization to the ketone-like C–H product.
- [1,2]-H shift
- Direct migration of hydrogen to an adjacent carbon; calculated here as too high in energy.
Flashcards
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Quiz yourself
Which site of phenol is computed as most favorable for gold-carbene C–C coupling with (PhO)3P?
Common questions
Why does para-C–H beat O–H insertion with (PhO)3PAu?
The C–H intermediates and product are more stable, and the water-assisted hydrogen transfer is lower in energy than the O–H path.
What does water do?
Two water molecules shuttle the proton from the enol to the final C–H product; a direct [1,2]-H shift is ~30 kcal mol–1.
How does the phosphite ligand help?
Oxygen atoms on (PhO)3P hydrogen-bond to the shuttle waters and stabilize that transition state.
What happens with Ph3P instead?
C–H addition gets harder and O–H insertion gets easier, matching the ligand-dependent chemoselectivity.
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