Photoinduced Copper-Catalyzed
C–N Couplings
B4 Yu Irie
2021/11/17 (Wed)Table of Contents
1.
2.
3.
4.

Introduction
Enantioconvergent C–N couplings from carbazoles
C–N couplings independent of nucleophiles by designing a ligand
Enantioconvergent C–N couplings independent of nucleophiles byusing 3 ligands
5. Summary and perspective

2

Table of Contents
1.
2.
3.
4.

Introduction
Enantioconvergent C–N couplings from carbazoles
C–N couplings independent of nucleophiles by designing a ligand
Enantioconvergent C–N couplings independent of nucleophiles byusing 3 ligands
5. Summary and perspective

3

Enantioconvergent Synthesis of Amides
via Radical Intermediates

J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

4

Synthesis of Enantioenriched Amides*Both strategies require enantiopure
substrates.

Expanding the scope by N-alkylation
via classical pathways (SN1 or SN2) ischallenging.
J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

5

Limitations of Approach via N-alkylation+ Stereoselectivity problems: SN1 reaction gives racemic products, andSN2 reaction requires pure enantiomers as SM.
G. C. Fu, ACS Cent. Sci. 2017, 3, 692.

6

Approach via Radical Intermediate

Transition-metal catalysis via radical
intermediates could enable
enantioconvergent reactions of racemic
halides.

G. C. Fu, ACS Cent. Sci. 2017, 3, 692.

7

About the Authors (G. C. Fu)
・Nickel Catalysis: Metal-catalyzed coupling
reactions of alkyl electrophiles

up to 94% ee

Gregory C. Fu
Caltech(Professor of Chemistry)
G. C. Fu et al. J. Am. Chem. Soc. 2008, 130, 6694.

Enantioconvergent reaction
from racemic alkyl halides
via radical intermediate・Copper Catalysis: Couplings of nitrogen
nucleophiles with alkyl electrophiles (with Petersgroup)
http://fugroup.caltech.edu/research.html

8About the Authors (J. C. Peters)
・Photoinduced Copper-Catalyzed C–N Coupling
・Investigation of Iron-Catalyzed
Nitrogen/Ammonia Cyclingetc.

Jonas C. Peters
Caltech(Professor of Chemistry)

https://jcpgroup.caltech.edu/research

9

Photoinduced C–N Ullmann Coupling

CuI (10 mol%)hν(100-watt Hg lamp)
Ph I

Li N

rt, 10 h
MeCN

Ph N

Using the light energy, the reaction proceeds under unusually
mild conditions (room temperature or even –40 ˚C).

J. C. Peters, G. C. Fu et al. Science. 2012, 338, 647.

10

Classical Ullmann Coupling
General scheme of C–N
Ullmann coupling

Two possible pathways for Ullmann C–N bond formation

Photoinduced C–N coupling was thought to proceed via SET pathway.
J. C. Peters, G. C. Fu et al. Science. 2012, 338, 647.

11

Possible Pathway for Photoinduced C–N Coupling

LnCuⅠ(NR2)X

CuI (10 mol%)hν(100-watt Hg lamp)
Ph I

Li N

rt, 10 h
MeCN

hν

NR2

Ph N

LnCuⅠ(NR2) *LnCuⅠXAr NR2

reductive
elimination

LnCuⅢAr(NR2)

Ar X

SET

X

LnCuⅡ(NR2)X

Ar･J. C. Peters, G. C. Fu et al. Science. 2012, 338, 647.

12

Effects of Changes in Reaction Parameters*Yields of purified productare in parentheses.

Entry 2,3: Light and catalyst arenecessary for the reaction toproceed.
Entry 6: CuI also serves as acatalyst. (The reaction proceeds
likely via electron transfer froma luminescent copper–
carbazolide complex generated
in situ.)

Results of several experiments (X-band EPR spectrum/Cyclization in aphotoinduced condition/Stereochemical study) are consistent with thepathway via radical intermediates.
J. C. Peters, G. C. Fu et al. Science. 2012, 338, 647.

13

Confirmation of a Radical Pathway:
About X-band EPR Spectra
EPR is the observation of the resonance when unpaired electrons of aparamagnetic substance absorbs the microwaves (especially on Xband) during spin transition.

When the energy difference
corresponds to the energy of
microwaves, electrons absorb theenergy of them.

https://www.jaima.or.jp/jp/analytical/basic/magneticresonance/esr/
https://www.oceanochemistry.org/publications/TRIOC/PDF/trioc_2006_19_113.pdf

14Confirmation of a Radical Pathway:
X-band EPR Spectrum
reaction condition

R 3P
Cu N
R 3P

PhI
hν
(100-watt Hg lamp)

SET−40˚C, 15min

Photolysis
LnCu N

Magic Blue (0.3 eq.)

Oxidation

LnCu

N
N

Cu Ln

−10˚C

(R = m-tol)

Br

Br

N

N

Br

Br

Br

detected?

Br

SbCl6
Magic Blue
(one-electron oxidant)

The same radical species can be generated by chemical and by photoinduced oxidation.
J. C. Peters, G. C. Fu et al. Science. 2012, 338, 647.

15

Confirmation of a Radical Pathway:
Cyclization in a Photoinduced Condition
Radical 5 is known to cyclize
very rapidly[rate constant (k) = 9.6 × 109
s−1 in dimethyl sulfoxide].
Consistent with aradical pathway*This product can be generated via
concerted oxidative addition of 4 to form
an aryl–copper reagent, followed by syninsertion and reductive elimination.
→ Needs further investigation
J. C. Peters, G. C. Fu et al. Science. 2012, 338, 647.

16

Confirmation of a Radical Pathway:
Stereochemical Study
I

D

R 3P
Cu N
R 3P

O

hν
(13-watt CFL)
rt, MeCN
43%

D

D
N

O

O
1:1

(R = m-tol)oxidative
addition

N
CuLnI
O

N

Fully consistent
with a radical
pathway

reductive
elimination

Ln
CuI

syn-insertion
O

D
N

D

J. C. Peters, G. C. Fu et al. Science. 2012, 338, 647.

17

Substrate-Competition Study to Confirm
a Pathway Involving SETBr

NC→ Consistent with a radical-based SET
pathway for C–N bond formationCloxidative
addition

SET(reduction
potential)

○

△

△

(–2.17 V)○(–2.03 V)*reduction potential:
versus SCE in DMF
J. C. Peters, G. C. Fu et al. Science. 2012, 338, 647.

18

Expansion of Substrate Scope of
Photoinduced C–N Coupling
・Carbazoles＋Alkyl halides
CuI (10 mol%)hν(100-watt Hg lamp)
N Li

Ph I

N Ph

MeCN
r.t., 10 h

1.2 eq.

N H

I

CuI (10 mol%)hν(100-watt Hg lamp)

R1

LiOt-Bu (1.9 eq.)
MeCN
0˚C

R2

J. C. Peters, G. C. Fu et al. Science. 2012, 338, 647.

1.2 eq.

R

N

R1
R2

R

J. C. Peters, G. C. Fu et al. Angew. Chem. Int. Ed. 2013, 52, 5129.

・Various nitrogen nucleophiles＋Aryl halides

・Amides＋Alkyl halidesR

CuI (10 mol%)hν (254 nm)

R1

O
NH2

X

R2

2.0 eq.
X = Br, I

R
2.0 LiOt-Bu
MeCN/DMF
r.t.

X

R1

O
N
H

CuI (10 mol%)hν (254 nm)

R2

J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2014, 136, 2162.

NH
an indole,
bezimidazole,
imidazole,or carbazoleArI

1.4 eq.

1.4 LiOt-Bu
MeCN or
MeCN/t-BuOH
r.t., 24 h
X = CH, N

X
N
Ar

19

J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2013, 135, 13107.

Expansion of Substrate Scope of
Photoinduced C–N Coupling
・Carbazoles＋Alkyl halides
CuI (10 mol%)hν(100-watt Hg lamp)
N Li

Ph I

N Ph

MeCN
r.t., 10 h

1.2 eq.

N H

I

CuI (10 mol%)hν(100-watt Hg lamp)

R1

LiOt-Bu (1.9 eq.)
MeCN
0˚C

R2
1.2 eq.

R

N

R1
R2

R

substrates were applied in
J. C. Peters, G. C. Fu et al. Science.Various
2012, 338, 647.
J. C. Peters,
G. C. Fu et al. Angew. Chem. Int. Ed. 2013, 52, 5129.
the reaction with similar
mechanism.
→ The next challengeis・Various
nitrogen nucleophiles＋Aryl halides
・Amides＋Alkyl halides enantioconvergent reaction.
CuI (10 mol%)
R1

O
R

CuI (10 mol%)hν (254 nm)

NH2

X

R2

2.0 eq.
X = Br, I

2.0 LiOt-Bu
MeCN/DMF
r.t.

R1

O
R

X

N
H

R2

J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2014, 136, 2162.

NH
an indole,
bezimidazole,
imidazole,or carbazoleArhν (254 nm)

X

1.4 LiOt-Bu
MeCN or
MeCN/t-BuOH
r.t., 24 h
X = CH, N

N
Ar

I

1.4 eq.

20

J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2013, 135, 13107.

Table of Contents
1.
2.
3.
4.

Introduction
Enantioconvergent C–N couplings from carbazoles
C–N couplings independent of nucleophiles by designing a ligand
Enantioconvergent C–N couplings independent of nucleophiles byusing 3 ligands
5. Summary and perspective

21

Enantioconvergent C–N Couplings from Carbazoles

22

J. C. Peters, G. C. Fu et al. Science. 2016, 351, 681.

Possible Reaction Pathway

It is almost the same with the previous reactions.
J. C. Peters, G. C. Fu et al. Science. 2016, 351, 681.

23

Effect of Changes in Reaction Parameters

High ee was achieved by adding thechiral ligand, thereby proving that aphosphine (L*) binds to a copper inthe presence of the nucleophiles
which are also likely to bind to acopper.
*They are taking advantage of thephotocatalyst, which doesn’t workwithout phosphine binding to a copper(entry 5).
J. C. Peters, G. C. Fu et al. Science. 2016, 351, 681.

24

Investigation of Kinetic Resolution

The chiral ligand determines theabsolute configuration of thestereochemistry very effectively, and
C–Cl bond cleavage is irreversible.

O
N

Cl
Et Ph

O

O
N

N

Cl
Et Ph

Et
Ph

no racemization

J. C. Peters, G. C. Fu et al. Science. 2016, 351, 681.

25

Plausible Intermediate in the Catalytic Cycle

1
Plausible intermediate

Irradiation of complex 1 in the presence ofa racemic tertiary alkyl halide leads to C–Nbond formation in good yield and withenantioselectivity.
Plausible intermediate

J. C. Peters, G. C. Fu et al. Science. 2016, 351, 681.

26

Substrate Scope

Electrophiles
CuCl (1.0–5.0 mol%)(S)–L* (1.2–6.0 mol%)hν (blue LED)

O
Cl

R 2N

Nucleophiles

HN
LiOt-Bu (1.5 eq.)
toluene, –40 ˚C

R R1
racemic
1.2 eq.

O

O
R 2N

CuCl (1.0–5.0 mol%)(S)–L* (1.2–6.0 mol%)hν (blue LED)

N

Cl

N

R R1

HN

N

N

LiOt-Bu (1.5 eq.)
toluene, –40 ˚C

Et Ph
racemic
1.2 eq.

O
Et Ph

X
Me

O
N

O
N

O
N

N

Bn Ph

Me
Me

MeO

N
Me

O
N
Me

N

X

Me

O
N

Et Ph

Et

N

O
N

Et Ph

N

N
Et Ph

OMe

Me
77% yield, 94% ee

90% yield, 87% ee

73% yield, 95% ee

95% yield, 92% ee

79% yield, 92% ee

86% yield, 88% ee

J. C. Peters, G. C. Fu et al. Science. 2016, 351, 681.

27

Short Summary• Enantioconvergent C–N couplings were attained.
• Substrates are limited to carbazoles and indoles (since visible light isused for irradiation).

• Expansion of the nucleophile scope requires new strategy.
J. C. Peters, G. C. Fu et al. Science. 2016, 351, 681.

28

Table of Contents
1.
2.
3.
4.

Introduction
Enantioconvergent C–N couplings from carbazoles
C–N couplings independent of nucleophiles by designing a ligand
Enantioconvergent C–N couplings independent of nucleophiles byusing 3 ligands
5. Summary and perspective

29

Expanding Nucleophile Scope by Designing a Ligand

This reaction can be applied
not only to carbazoles andindoles but also tocarbamates.
*Not enantioconvergent

J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

30

Selective Mono-Alkylation of a Primary Carbamate

cf. J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2014, 136, 2162.

・Inefficiency of the alkylation
・Need for high-energy ultraviolet irradiation
・Use of an excess of the electrophile→ To enhance the reactivity under a mild condition, using visible
light (though the substrate is limited so far) may be effective.
J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

31Limitations on Substrates in Previous Approach
Using Visible Light
The photophysical properties of thecopper-nucleophile complex are
dependent on the structure of thenucleophile (only carbazoles andindoles are applicable so far).

*Example of the complexes that canabsorb relatively long-wavelength lights
J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

32

Solution: Development of a Photocatalyst
Bond formation

Radical generation

Two different types of copper catalysts would be generated in situ:
1. Catalyst (E) that serves as a photoredox catalyst ← designed this time
2. Catalyst (A) that facilitates the bond formation
J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

33

Design of a New Photocatalyst*Catalysts such as 2a (2012
Science) and 2b (2016 Science)
can react to form C–N bonds
upon irradiation with relatively
long-wavelength light.

→ Linking these ligands, they made a copper complex which・is stable to ligand substitution・can serve as an effective photocatalyst which works upon
exposure to visible light independent of the nucleophile.
J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

34

Estimation of the Reduction Potentialof the Excited State: The Method
Cu(Ⅰ)*

E00: estimatedfrom excitation andemission spectra

reduction potentialof the excited state

Cu(Ⅱ)
Cu(Ⅰ)

estimated fromcyclic voltammogram

The transition energy between the lowest
energy vibrational state (v = 0) of S1 tov = 0 of S0

D. A. Nicewicz et al. Chem. Rev. 2016, 116, 10075.

35

Estimation of the Reduction Potentialof the Excited State: Estimation of E00

E00 is normally estimated at the intersection
between normalized symmetrical absorbanceand emission spectra.

In this case, E00 seems to havebeen estimated from thefluorescence maximum: 400 nm→ corresponds to 3.1 eV

https://www.an.shimadzu.co.jp/sites/an.shimadzu.co.jp/files/ckeditor/uv/support/lib/uvtalk/pdf/vol17.pdf
J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.
D. A. Nicewicz et al. Chem. Rev. 2016, 116, 10075.

36

Estimation of the Reduction Potentialof the Excited State: Estimated Results
CuⅠ

CuⅡ

Cu(Ⅰ)*

E

E00: 3.1 eV–2.5 V

Cu(Ⅱ)
0.6 V
Cu(Ⅰ)

Cyclic voltammogram of copper complex 1 in
THF (100 mV/s scan rate; 0.1 M in TBAPF6)

A cyclic voltammogram shows a reversible
wave at ∼0.6 V (vs. SCE).

E00: 3.1 eV
Ground-state redox couple : ~0.6 V
Predicted reduction potential :–2.5 V (vs. SCE) ≒ −2.6 V (complex 2a)

J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

37

Stern-Volmer Luminescence Quenching

*

t-Bu

t-Bu

P(i-Pr)2

P(i-Pr)2

N CuⅠ

N CuⅡ

electron transfer

P(i-Pr)2Br

P(i-Pr)2

t-Bu

t-Bu
Me
Br

Me
Bn

Bn

The quenching of the emission at 427 nm was confirmed.
→ The excited state of the designed photocatalyst is capable ofreducing the alkyl bromide.
J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

38

The Role of the Designed Photocatalyst

Excess CuBr → Copper complex 1 may beserving the typical role of photoredox catalysts
and not directly involved in the key bondforming process.

J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

39

Radical Cyclization Experiment
The rate constant of the cyclization of alkyl
radical: 1.0 × 105 s−1< Typical rates of diffusion: more than 108 s−1→ Consistent with the proposed mechanism
showing that after radical being generated, it
diffuses before coupling

The same stereoselectivity with thecyclization of the secondary alkyl radical

J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

40

Substrate Scope

CarbamatesRO

L1 (1.0 mol%)
CuBr (10 mol%)hν (blue LED)

Me

O
NH2

LiOt-Bu (3.0 eq.)
DME, rt.

3.0 eq.

MeO

Me
N
H

90% yield

RO

Bn

t-BuO

N
H

87% yield

O
Bn

BocNH2BrR2

3.0 eq.

Me

O

Bn

N
H

L1 (1.0 mol%)
CuBr (10 mol%)hν (blue LED)

R1

Me

O

Bn

Br

O

Electrophiles

O

Me

Me
N

LiOt-Bu (3.0 eq.)
DME, rt.

Bn

74% yield

BocHN

R2

Me

BocHN

BocHN
81% yield

R1

OMe

OTBS

72% yield

BocHN
81% yield

J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

41Short Summary• By designing a ligand, nucleophile scope were expanded tocarbamates other than carbazoles and indoles.
• The newly designed photocatalyst can work independently as aphotocatalyst, and basically does not participate in bond forming
process.

• Enantioselective reaction with expanded scope may be attained bydeveloping a new strategy which includes a chiral catalyst.
J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 18101.

42

Table of Contents
1.
2.
3.
4.

Introduction
Enantioconvergent C–N couplings from carbazoles
C–N couplings independent of nucleophiles by designing a ligand
Enantioconvergent C–N couplings independent of nucleophiles byusing 3 ligands
5. Summary and perspective

43

Enantioconvergent Reaction
with Expanded Scope by Using 3 Ligands

They succeeded in developing an enantioconvergent reaction
which is independent of the nucleophiles by using 3 ligands: abisphosphine, a phenoxide and a chiral diamine.
J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

44

Possible Catalytic Cycle

The reaction mechanism is similar to that of a previous reaction(cf. p.32, 2017 JACS).

J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

45

Investigation of Possible Photocatalysts
Possible photocatalysts: The electrophile is consumed in the absence of diamine N1*
but not in the absence of bisphosphine P. → PCuI(OPh) and PCuI(amidate)

To compare these two,・Estimated excited-state reduction potentials
・Excited-state lifetime measurement
・Stern-Volmer luminescence quenchingwere investigated.
J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

46

Results of the Investigation of Possible
Photocatalysts (PCuI(OPh) or PCuI(amidate))
PCuI(OPh)

PCuI(amidate)

Estimated excited-state
reduction potential* (vs Fc+/Fc)–2.8 V–2.3 V

Excited-state lifetime
measurement

4.6 μs2.4 μsStern-Volmer constant

189 M–1

25.2 M–1*The estimated reduction potential of the representative electrophiles: –2.3 V and –2.4 V (vs Fc+/Fc)

These results point to PCuI(OPh) complex as the more likely photocatalyst
under the reaction condition.
J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

47

Investigation of the Reaction where Two Catalytic
Cycles Intersect (D&G→B&E)
Two plausible mechanisms
1.

SET

P

P
CuⅠ

CuⅡ(OPh)X
P

P
D

N

B

N
CuⅠ X

N

CuⅡX2
N

G

2.

OPh

E

ligand exchange

P

P
CuⅠ

CuⅡ(OPh)X

OPh

P

P
D

N

B

N
CuⅠ X

N

CuⅡX2
N

G

E

J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

48

1. SET Mechanism:
Prediction of Redox Potentials→ Consistent with SET mechanism
SET

P

P
CuⅠ

CuⅡ(OPh)X

OPh

P

P
D

N

B

N
CuⅠ X

N

CuⅡX2
N

G

E

J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

49

2. Ligand Exchange Mechanism:
EPR Studies→ Consistent with rapid ligand
exchange (P → N2*) upon oxidationof CuI to CuII
ligand exchange

P

P
CuⅠ

CuⅡ(OPh)X
P

P
D

N
N

P
CuⅠ

OPh

P

P
P

Magic
Blue

Magic
Blue

CuⅡ(OPh)2N
N

CuⅡ(OPh)2

CuⅡX2
N

G

ligandexchange

B

N
CuⅠ X

one-electronoxidation

OPhE

1. SET
2. Ligand exchange→ Either or both of these are operative.
J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

50

Substrate Scope (Amides)

EtO

OEt
P
O

Br

O
Et

H 2N

R

OEt
P
O

CsOPh•H2O (1.5 eq.)
Cs2CO3 (1.5 eq.)(i-Pr)2O, –20 to –5 ˚C

95% yield, 93% ee

OEt
P
O

HN

CF3

EtO

OEt
P
O

O

76% yield, 90% ee

EtO

OEt
P
O

CF3

PAr2
PAr2

MeO
MeO

MeHN
(rac)-P
Ar = (3,5-di-t-butyl)phenyl

O

HN
Et

R
Et

O

HN
Et

O
EtO

O
EtO

F3C

Cu(CH3CN)4PF6 (12 mol%)(rac)-P (5 mol%), N1* (15 mol%)hν (blue LED)

HN

O
Me

Et

62% yield, 91% ee

EtO

OEt
P
O

H

HN
Et

Me Me

NHMe
N1*

H
H

H

H

Me

O

Lithocolic acid derivative(R,R)-N1*: 78% yield, 93:7 d.r.
[(S,S)-N1*: 73% yield, 5:95 d.r.]

J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

51

A Strategy to Differentiate Between Two Similar
Substituents

A Lewis-basic functional group of the alkyl halide provides a twopoint interaction between the substrate and the chiral catalyst.
→ Other than phosphonate, an amide, ester, ketone, sulfone,
sulfonamide and phosphine oxide can work as well.
J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

52

Substrate scope (Alkyl halides)

Br
DG

O

1,2 R

O

CF3

CsOPh•H2O (1.5 eq.)
Cs2CO3 (1.5 eq.)(i-Pr)2O, –10 or –5 ˚C

O
HN

1,2 R

CF3

Ar1
Me

Phosphonate
96% yield, 92% ee

HN
N

MeHN
(rac)-P
Ar = (3,5-di-t-butyl)phenyl

O

O
Ar1

Me
O

Amide
85% yield, 89% ee

EtO

NHMe

MeHN

N1*

Et
O

Ester
76% yield, 87% ee

t-Bu

O
Ar1

HN

NHMe
N2*

O
Ar1

HN

CF3

PAr2
PAr2

MeO
MeO

HN
DG

H 2N

OEt
EtO
P
O

F3C

Cu(CH3CN)4PF6 (12 mol%)(rac)-P (5 mol%), N* (15 mol%)hν (blue LED)

Et
O

Ketone82% yield, 92% ee

Ar1

HN
i-Pr

S
O O

Et

Sulfone62% yield, 92% ee

J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

53

Short Summary

Enantioselective reaction with expanded scope was attained by
exploiting three ligands.
J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

54

Table of Contents
1.
2.
3.
4.

Introduction
Enantioconvergent C–N couplings from carbazoles
C–N couplings independent of nucleophiles by designing a ligand
Enantioconvergent C–N couplings independent of nucleophiles byusing 3 ligands
5. Summary and perspective

55

Summary
Copper-catalyzed
photoinduced C–N coupling

Enantioconvergent reaction(restrictions on nucleophiles)

Enantioconvergent,nucleophile-independent
C–N coupling by using 3
ligands

Nucleophile-independent
reaction by designing a
new photocatalyst
J. C. Peters, G. C. Fu et al. Nature. 2021, 596, 250.

56

Perspective• Expansion of substrate scope• Other N-nucleophiles (e.g. aliphatic
amines)The bond-formation step which
determines the stereochemistry
may be challenging.
J. C. Peters, G. C. Fu et al. J. Am. Chem. Soc. 2017, 139, 17707.

• Tertiary alkyl halides
Substrates which have electronwithdrawing groups (such as
those used in 2016 Science) may
be applied.

O
R1

O
X

R2 R3

racemic

OR4

H 2N
O

R1

H
N

OR4

R2 R3 O

→ A new way to synthesize
unnatural amino acids
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