Science - USA (2022-04-29)

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
  
  
  
  

(% 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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