was also found to be amenable to a one-pot
process, with initial formation of theN-oxide
induced by hydrogen peroxide in dichloro-
methane followed by dilution of the crude
reaction mixture with toluene (95:5) before
irradiation affording theN-acylindole in only
slightly diminished yields (69%) relative to the
two-pot procedure with purifiedN-oxide (78%).
As noted above, this transformation was found
to be robust to a wide variety of functionality
commonly encountered in medicinal chemis-
try, including other heterocycles (2d,2e,2f,
SCIENCEscience.org 29 APRIL 2022¥VOL 376 ISSUE 6592 529
N CN
O
N
O
CN
B
N •
O
CN
or
C 6 D 6 , 25 oC
C
D
E
1b
3b
N
(^18) O
Me
C 6 D 6 , 25 oC
N
- Me
O
[^18 O]-3a
(generated in situ
from 93%^18 O 1a)
2a, 78%
N •
(^18) O
Me
H
TFA
66% 18 O
H 2 O
N
- Me
O
1a
N •
O
Me
3a, 91% (NMR)
15:1 3a/4a
C 6 D 6
25 oC
N •
(^18) O
Me
H 2 O
NH
(^18) O
Me O
NH
O
Me^18 O
N •
O
CN
N
- CN
O Toluene
25 oC, 1 h 3b, 83%
≡
1b [X-Ray]
390 nm
LED
H
H H
LED-NMR at
70% conversion
390 nm
LED
Hypothesis
selective excitation
averts side reactions
N
- O
quinoline
N-oxide
Hg Lamp
N
- O N •
O
N
O
3,1-benzoxazepine
harsh, broadband
UV light source
N
- O
N
OH
- O
NH
- O
O
N
H
H 2 O
O
hydration products
(carbon deletion)
N
H
- O N
- N O
OH
oxaziridine
N
H
O
N
- O
2,1-benzoxazepine
N
H
- limited scope
- highly substrate-
dependent - low yields
suspected two-photon byproducts
hv
A Classical N-Oxide Photochemistry
+
photon #1
hv photon #2
Buchardt, Kaneko,
Streith, Albini
(1966-1987)
- H 218 O
- H 2 O
3b
- H 2 O
(% remaining)
Time (h)
Fig. 2. Mechanistic basis for light source effects in quinolineN-oxide pho-
tochemistry and mechanism of acid-promoted benzoxazepine rearrangement
to indole.(A) Summary of classical photochemical rearrangements promoted by
broadband mercury lamp irradiation. (B) LED-NMR study of 390-nm LED photolysis of
1aand isolation of 2-cyano-3,1-benzoxazepine (3b) from LED photolysate of quinoline
N-oxide1b. ppm, parts per million. (C) Photostability study of3bunder LED and Hg
lamp irradiation. (D) Ultraviolet–visible absorption spectra of1band3bwith overlaid
relative emission spectra of 390-nm Kessil lamp and 200-W medium-pressure Hg
lamp (normalized to an emission intensity of 1 forlmax). (E) Labeling study of
trifluoroacetic acid (TFA)–promoted rearrangement of3a.
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