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Peng et al. Sci China Chem May (2021) Vol.64 No.5
strate for ring contraction and rearrangement reactions (Ta-
conditions, the optimal reaction was determined by trigger-
ing the reaction with RhB (PC1) as a catalyst, air as an
oxidant, and NaOH as a base in a mixed solvent of CH3CN
and 1,4-dioxane (4:1 v/v) at room temperature under the ir-
radiation of green LED strip (15 W), thereby gaining 3-
aldehyde pyrrole 2a in 72% yield (entry 1). The use of a
single solvent, such as CH3CN or 1,4-dioxane (entries 2‒3),
led to a very low yield. The reactions were not effectively
performed in other photocatalysts, such as cobalt tetra-
methoxyphenylporphyrin (PC2), Ru(bpy)3Cl2·6H2O (PC3),
and eosin Y (PC4), with yields in trace-14% (entries 4‒6).
Product 2a was not obtained without the base and the lack of
the PC or light also resulted in significantly lower yields
(entries 7‒9). Interestingly, when PC2 and 1-benzylpyr-
idinium bromide 1a, instead of PC1 and 2-phenylpyridinium
bromide 1b, were applied to the system, the reaction afforded
the rearrangement product 3a. Moreover, CH3CN/DCE (1:1
v/v) mixed solvent was suitable for the ring contraction re-
action (see Supporting Information online). For this reaction,
the main by-product was pyridines.
C–C bond cleavage and recyclization using RhB as a pho-
tocatalyst (Scheme 1). When pyridinium substrates with a
phenyl group on the C2 position of the pyridine moiety were
used, R1 benzyl groups bearing various substituents with
diverse electronic properties, including electron-donating
groups, such as methyl, tert-butyl, phenyl, and methoxy, and
electron-withdrawing groups, such as fluoro, chloro and
cyano, were well proceeded the current protocol, giving 3-
aldehyde pyrroles 2a–2k in 62%–78% yields. N-substituted
(R1=phenethyl, benzylidene) pyridinium salts were also
tolerated to afford 2l and 2m. R1 groups bearing alkyl, such
as methyl, allyl, and hexyl, were compatible to obtain 3-
aldehyde pyrroles 2n, 2o, and 2p, respectively. Similarly, R1
groups with naphthalene and heterocycle smoothly gave the
corresponding desired products 2q and 2r. The halogenated
pyridiniums (X=Cl, I) were also successfully converted into
the target compounds (2a, 2g, 2i, and 2n). When pyridinium
substrates with other groups (methyl and benzyl) on the C2
position of the pyridine moiety were used, products 2s and 2t
were obtained in 32% and 60% yields, respectively. Low
reactivity was universally observed when using N-sub-
stituted (R2=H) substrates under ring contraction reactions
(2u and 2v) due to simultaneous emergence of the by-
products of 4-carbonyl pyridines. When R1 groups with alkyl
substituent or aryl group with large steric resistance were
employed, the migrated products were efficiently inhibited
and the ring contraction reaction ran smoothly in the opti-
mized system, affording 3-aldehyde pyrroles 2w and 2x in
modest yields. Moreover, the structure of 2x was determined
by using X-ray diffraction (CCDC 1974519). The pyr-
idinium substrates with chloro, acetyl and methoxy on the C2
or C3 position, as well as the 2,6-dimethyl pyridinium were
failed to participate in this reaction.
After establishing the condition, we next explored the
substrate scope of oxygen-mediated and visible light-driven
Having obtained the remote C(sp3)–H bond activation of
4-carbonyl pyridines, we next investigated the substrate
scope of remote C(sp3)–H rearrangement by using PC2 as a
catalyst. As shown in Scheme 2, under the optimized con-
ditions, substituents at the benzyl motif reacted smoothly to
form 4-carbonyl pyridines with moderate to good yields
(35%–64% yield) (3a–3p). The benzyl group bearing elec-
tron-rich or electron-deficient groups, such as methyl (3b–
3e), methoxy (3f), ester (3g–3h), and halogen (3i–3m),
successfully afforded the desired products. Even the strong
electron-withdrawing groups, such as trifluoromethyl, cyano
and nitro, were amenable to the rearrangement/oxidation
protocol and provided 4-carbonyl pyridines (3n, 3o and 3p).
Different halogenated pyridiniums (X=Cl) were also adapted
in the rearrangement reaction (3a, 3f and 3k). Moreover,
naphthalene and heteroaromatics, such as thiophene, were
successfully applied to the transformation (3q and 3r). Al-
though we attempted to use the various substituents at the
pyridine motif, no desired products were detected.
Variation from standard
Entry
2a (%)b)
conditions
1
2
3
4
5
6
7
8
9
none
72
8
CH3CN
1,4-Dioxane
PC2
13
trace
8
PC3
PC4
14
without base
without PC
in the dark
NR
< 5
16
a) Reaction conditions: 1-benzylpyridinium bromide 1b (0.20 mmol),
NaOH (3.0 equiv.), catalyst (5.0 mol%), LED strip as light source (see
Supporting Information online for additional details), ambient temperature,
10 h, under air atmosphere. b) Isolated yield.
As a radical trap, the addition of 2,2,6,6-tetramethyl-1-