Science - USA (2021-12-03)

underscoring the capacity of the SH2 mecha-
nism to generally construct sterically hin-
dered centers. Redox-active esters containing
electron-deficient backbones (i.e., azetidine
and difluoropyrrolidine) were found to be vi-

able coupling partners and underwent alkyl-

ation in good yields ( 17 to 19 , 46% to 69%

yield). In addition, bulkya-functionalized

exocyclic or acyclic amines could be accessed

via cross-coupling in good efficiency ( 20 and

21 , 64% and 51% yield). Furthermore, the

use of tertiary redox-active esters enabled

the formation of quaternary carbons, as rep-

resented in the acyclictert-butyl moiety and

a cyclicb-substituted pyrrolidine, as well as a

SCIENCEscience.org 3 DECEMBER 2021¥VOL 374 ISSUE 6572 1261

-amino carboxylic esters

CbzHN NHBoc

O

Me Me

NHBoc

Cl

Cbz

N

Me NHBoc

(±)- 16 , 80% yield

22 , 47% yield

(±)- 15 , 71% yield (±)- 17 , 46% yield* (±)- 19 , 61% yield

25 , 50% yield*

alkyl bromides

24 , 60% yield

18 , 69% yield,

20 , 64% yield (±)- 23 , 63% yield

tertiary carboxylic esters

26 , 68% yield

N

Boc

Me

O

HN

O

N

Boc

F Me

F

O

HN

O

S

Me

O NH O

O O

N

NHCbz

Boc

• oxy carboxylic esters

BocHN

secondary carboxylic esters

N

NHBoc

Cbz

28 , 65% yield (±)- 29 , 50% yield

CbzHN NHBoc

Me Me

21 , 51% yield

Me O NH O

Me

Me

N

Cbz

NHBoc

Fe(OEP)Cl (2 mol%)

(TMS) 3 SiNHAdm, KOAc

Ir photocatalyst 11 (1 mol%)

acetone : iPrOH (1:1)

blue LEDs, 2 h

N

Cbz

Me

O

O

NPhth

N

Cbz

NHBoc

Me

Me

N

Boc NHBoc

Cl

N

O

Cbz

(±)- 27 , 56% yield

Me

N

Cbz

Me

Cl

N

Cbz

Me

NHBoc

(±)- 32 , 71% yield

N

Cbz

Me

O

N

N

MeO

N

Cbz

Me

O

NN

CO 2 Et

36 , 70% yield

(±)- 41 , 75% yield (±)- 45 , 63% yield

37 , 52% yield

(±)- 42 , 52% yield

N N

N

CH 3

Me

N N

N

Cl

Me

N N

N

NHBoc

Me

33 , 63% yield

DD

(±)- 44 , 68% yield

(±)- 34 , n = 1, 33% yield

(±)- 39 , 74% yield

(±)- 43 , 65% yield||

N

Cbz

Me

NBoc

N

Cbz

OMe

NBoc

(±)- 30 , 59% yield

N N

N

Me

31 , 84% yield

Me

N

Cbz

Me

(^13) CD 3 N
Boc Me
Cl
N
Cbz
Me
OMe
O
(±)- 35 , n = 3, 76% yield
(±)- 10 , 70% yield
Boc
N
Me
O
H
N O
2
38 , 47% yield
N
MeO
Cbz
NHBoc
CbzN
OMe
OMe
HN O
4
then NaH
Fe
Br Cl
N
N
Boc
Cbz
N
Cbz
N
Cbz
Ir
CbzHN ON
O
CbzHN ON
O
accelerated access to spirocyclic saturated heterocycles
N
Cbz
Me

• O
  75% yield of C(sp^33 ) product ( 14 )
  Br O
  HN O
  (^43) NH O additional examples in
  supplementary materials
  n
  then NaH
  Fe
  Br Cl
  Ir
  2
  then NaH
  Fe
  Br Cl
  Ir
  46 , 66% yield 47 , 98% yield 48 , 62% yield 49 , 99% yield 50 , 55% yield 51 , 85% yield
  N
  Boc
  ON
  O
  CbzHN
  NHAr
  Fig. 3. Photoredox and iron-catalyzed C(sp^3 )ÐC(sp^3 ) cross-coupling: Redox-active ester and alkyl bromide scope.All yields are isolated. See supplementary
  materials for detailed reaction conditions. TMS, trimethylsilyl group; Adm, 1-adamantyl; KOAc, potassium acetate;iPrOH, isopropanol; Ar, 3-chloro-4-fluorophenyl;
  N, phthalimide. With KOAc and Zn(OAc) 2 as bases.†With Zn(OAc) 2 as the base.‡With Ir(ppy) 2 (dtbbpy)PF 6 as the photocatalyst. §With 2 equivalents of
  methylp-toluenesulfonate and tetrabutylammonium bromide. ||With Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 as the photocatalyst. ¶Sodium hydride, 60°C.
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