Science - USA (2021-12-03)

medicinally important cyclic sulfone ( 22 to
24 , 47% to 63% yield) ( 41 ). Fora-oxy esters,
radicals generated adjacent to both phenoxy
and methoxy substituents could participate
in cross-coupling with respectable effici-
ency, providing a new entry to the synthesis
of hindered ethers ( 25 and 26 , 50% and 68%

yield). Finally, secondary redox-active esters

could also be used in our metallaphotoredox

protocol to couple with primary bromides in

good yields ( 27 to 29 , 50% to 65% yield). On

the other hand, tertiary benzylic radical was

found to be a challenging SH2 reaction part-

ner, presumably because of the diminished

radical nucleophilicity (see fig. S12 for ad-

ditional examples and limitations of sub-

strate scope).

Next, we examined the scope of alkyl bromides

using botha-heteroatom and tertiary redox-

active esters as the representative coupling

partners. Small alkyl fragments such as methyl

1262 3 DECEMBER 2021¥VOL 374 ISSUE 6572 science.orgSCIENCE

B

A

(10 mol%)

N

N

N

N

FeIII

Et

Et

Et

Et Et

Et

Et

Et

Me

Ir

N

Cbz

Me

4

O

H

O N

14 , 64% (±3) yield

54 , 7% (±1) yield

4

O

H

Br O N

N

Cbz

Me

O

O

N

+

N

Cbz

Me

O

O

independently prepared

n

N

N

N

N

FeIII

Et

Et

Et

Et Et

Et

Et

Et

Me

Ir Fe

N +

Cbz

Me

Br Me

54

CO 2 NPhth

Me

55

53

N

Cbz

Me

Me

t = 15 min

t = 30 min

t = 60 min

before irradiation

t = 3 min

t = 45 min

t = 90 min

t = 120 min

C

44% (±5) yield

N

Cbz

Me

O

O

NPhth

N

Cbz

Me

Me

Zn^0 , ZnCl (^2) (1 equiv.)
n
radical generationin the absence of light
53
dark
blue LED 42% (±7) yield
53
54
N
Cbz
Me
D
N
Cbz
Me
O
O
NPhth Br
NHBoc
Me
N
Cbz
Me
NHBoc
± Fe(OEP)Cl Me
standard condition

• 53 55 56
  0 mol% [Fe] 15% yield, 1:1.1 d.r.
  10 mol% [Fe] 56% yield, 3.2:1 d.r.
  evidence for Fe-mediated SH2 mechanism
  versus radical-radical coupling
  acetone-d 6
  Fig. 4. Mechanistic studies for the proposed catalytic cycle and evidence of the intermediacy of alkyl-Fe(III) species.(A) Observation of key alkyl-Fe(III)
  species under reaction conditions. (B) Use of alkyl-Fe(III) complex as reaction precatalyst. (C) Formation of CÐC bond under nonphotonic conditions. (D) Effect of iron
  porphyrin catalyst on diastereoselectivity of reaction.n-Bu,n-butyl group; ZnCl 2 , zinc chloride.
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