Merging Catalysis in Single Electron Steps with Photoredox Catalysis - Efficient and Sustainable Radical Chemistry

Article abstract of DOI:10.1021/acscatal.9b00787

We describe a combination of catalysts that allows the coupling of titanocene(III) catalysis with photoredox catalysis. Oxidation of radical intermediates by a photoredox catalyst opens novel catalytic mechanisms for reductive epoxide ring opening and redox-neutral epoxide radical arylation. In the former case, the requirement of metallic reductants and stoichiometric acidic additives is bypassed.

Full text of DOI:10.1021/acscatal.9b00787

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Letter
Merging Catalysis in Single Electron Steps with Photoredox
Catalysis – Efficient and Sustainable Radical Chemistry
Zhenhua Zhang, Ruben Richrath, and Andreas Gansaeuer
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b00787 • Publication Date (Web): 08 Mar 2019
Downloaded from http://pubs.acs.org on March 9, 2019
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Merging Catalysis in Single Electron Steps with Photoredox Catalysis –
Efficient and Sustainable Radical Chemistry
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Zhenhua Zhang, Ruben B. Richrath, and Andreas Gansäuer*
Kekulé-Institut für Organische Chemie und Biochemie Rheinische Friedrich Wilhelms-Universität Bonn Gerhard Domagk-
Straße 1, 53121 Bonn, Germany
KEYWORDS: electron transfer, photoredox catalysis, radical chemistry, sustainable chemistry, titanocenes
ABSTRACT: We describe a combination of catalysts that allows the coupling of titanocene(III) catalysis with photoredox
catalysis. Oxidation of radical intermediates by a photoredox catalyst opens novel catalytic mechanisms for reductive epoxide
ring opening and redox-neutral epoxide radical arylation. In the former case, the requirement of metallic reductants and
stoichiometric acidic additives is bypassed.
‘Catalysis in single electron steps’1 or ‘metalloradical
OH
O
Bn
Bn
catalysis’2 is a concept merging the advantages of radical
In the absence of PRC:
10 mol% Cp2TiCl: <5%
1
3
chemistry with those of transition metal catalysis. The
realization of this idea critically depends on the generation
of radicals and their transformation to the closed-shell
products through oxidative additions and reductive
eliminations in single electron steps.3 For both steps, the
metal catalyst is in principle, able to control the typical
selectivities exactly as in traditional transition metal
catalysis. However, the applicability of these catalytic
reactions is limited by the redox properties of the catalyst
that determine which oxidative additions and reductive
eliminations are possible. Therefore, it is highly desirable to
widen the ‘redox potential window’ of such catalytic
reactions in order to obtain more broadly applicable
processes. Here, we demonstrate that this idea can be
realized by merging Cp2TiX-catalyzed reactions with
photoredox catalysis. Despite the utility of titanocene-
catalyzed radical reactions, 4 an inherent limitation of this
methodology is arising from the reducing power of Cp2TiCl,
the most commonly employed catalyst.5 The titanocene(IV)
intermediates generated during radical generation are
often unable to undergo a reductive elimination because the
Ti(IV) species are not strong enough oxidants. We will show
how this limitation can be overcome with the aid of
photoredox catalysis (PRC) for two examples.
O
O
O
O
Coupling Titanocene Catalysis with PRC:
10 mol% Cp2TiX2, 1 mol% PRCat, blue LED ?
EtO
OEt
EtO
OEt
N
H
2
4
N
Pausible Mechanism for Coupling of PRC with Titanocene Catalysis
[PRCatn]*
[PRCatn+1]X
O
O
OH
+
EtO
OEt
Cp2TiX2
Bn
N
4
Cp2TiX
3
O
Bn
Titanocene Cycle
[Ti] = Cp2TiIV
1
O
H
O
X
EtO
OEt
O
D
O
[Ti]
N
[Ti]
A
Bn
H X
B
Bn
PRCatn
O
O
O
H
O
H
H
EtO
OEt
[PRCatn+1]X
EtO
OEt
2
N
N
H
C
H
Scheme 1. Coupled catalytic cycles for the reaction of 1 to 3 by
coupling of titanocene(III) and photoredox catalysis (PRC).
We anticipated that PRC6 can resolve this issue and at the
same time provide a means to generate the active Cp2TiX
catalyst by an oxidative quenching cycle. If the excited
photoredox catalyst [PRCatn]* is able to reduce Cp2TiX2 to
Cp2TiX, epoxide opening and reduction of the generated
radical A by 2 yields the titanocene alkoxide B and radical
σ–complex C. Through electron transfer from C to the
oxidized photoredox catalyst [PRCatn+1]X, PRCatn and D
are formed. Then, 3 is formed by protonation of the Ti-O
bond of B with D that also regenerates Cp2TiX2. Finally, after
irradiation with blue light [PRCatn]* is reformed that can
once again reduce Cp2TiX2 to Cp2TiX. The critical issue of
coupling PRC with titanocene catalysis is the matching of
the redox-potentials of the species involved in catalysis. The
excited [PRCatn]* must be able to reduce Cp2TiX2 and
[PRCatn+1]X must be able to oxidize C. Therefore, we
decided to screen a number of titanocene complexes and
often employed photoredox catalysts (Table 1). In
titanocene catalysis, a convenient way to modulate the
The first reaction examined is the reduction of epoxide 1
with Hantzsch-ester 2 to give alcohol 3 (Scheme 1). The
reaction should have a high thermodynamic driving force
due to the aromatization of 2 and the release of ring strain
in 1. However, Cp2TiCl is not able to catalyze the reduction
of 1 by 2 without additives. In the presence of 10 mol%
Cp2TiCl less than 5% of 3 are formed. We postulate that this
result is due to the inability of titanocene(IV) derivatives to
oxidize the radical σ–complex C to the cationic σ–complex
D. This highlights the problem associated with the low
oxidizing power of titanocene(IV) complexes.5
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Table 2. Substrate scope of the coupling of titanocene
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redox potential is to modify the ligand X.7 We investigated
-
-
the complexes with X = Cl-, CF3CO2 (TFA), CH3SO3 (OMs),
catalysis with PRC.
1
2
3
4
and pCH3C6H4SO3- (OTs).
6
(10 mol%)
R3 OH
R3
Table 1. Evaluation of Titanocene Complexes and
Photocatalysts for Coupling Titanocene Catalysis with
PRC.
11
(1 mol%)
O
R1
R2
2
R1 R2
5
blue LED
H
6
7
8
9
F3C
PF6
entry
1
substrate
product
yield/[%]
F
N
Ir
N
Ir
t-Bu
t-Bu
X
X
Ti
OH
N
N
F
F
O
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79
63
73
N
N
Ph
Ph
N
1
2
F
5: X= Cl, 6: X= TFA
7: X= OMs, 8: X= OTs
OH
F3C
O
2
3
10
11
fac-Ir(ppy)3
[Ir{dF(CF3)ppy}2(dtbpy)]PF6
Ti catalyst
Ir-photocatalysts
12
14
13
O
OH
Ti catalyst
photocatalyst
tBu
tBu
OH
O
2
4
+
+
Bn
trans : cis = 92: 8
Bn
10 W blue LED
15
1
3
tBu
tBu
4
70
HO
entry
Ti cat.
photocatalyst
3/[%]
30
O
d.r. = 89:11
17
1
2
3
4
5
6
7
8
9b
5
5
Ru(bpy)3Cl2•6H2O
fac-Ir(ppy)3
16
18
55
OH
O
5
[Ir{dF(CF3)ppy}2(dtbpy)]PF6
[Ir{dF(CF3)ppy}2(dtbpy)]PF6
[Ir{dF(CF3)ppy}2(dtbpy)]PF6
[Ir{dF(CF3)ppy}2(dtbpy)]PF6
none
60
60[b]
5
6
6
79
7
39
19
nHex
nHex
8
49
78
O
6
17
OH
cis : trans = 63 :37
none
6
[Ir{dF(CF3)ppy}2(dtbpy)]PF6
[Ir{dF(CF3)ppy}2(dtbpy)]PF6
n. r.
n. r.
20
21
OH
O
7
77
nBu
aconditions: Ti catalyst (10 mol%), photoredox catalyst (1
mol%), Hantzsch ester 2.0 eq, epoxide 0.05 M in THF, r.t., two
10 W blue LED. bno light.
nBu
nBu
nBu
22
23
OH
O
60[c]
8
9
OEt
EtO
OEt
With Cp2TiCl2 as precatalyst, Ru(bpy)3Cl2 9 gave a poor
yield of 3. The two Ir-complexes 10 and 11 resulted in a
better performance. Of the more electron deficient
precatalysts, 6 (X = TFA) gave the best result of all
titanocenes (79% isolated yield of 3). The presence of
Cp2TiX2, 11, and the irradiation with blue are all essential
for the success of the reaction. The coupling of PRC with
EtO
24
25
O
40[d,e]
HO
( )9
( )9
26
27
OH
O
( )8
R
( )8
R
titanocene catalysis is
a highly sustainable epoxide
reduction because it renders the stoichiometric system for
catalyst regeneration (Mn/Coll●HCl) under the previously
established conditions redundant.4c
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10
11
12
13
R=OTBS
R=OTs
R=OH
R=Cl
R=OTBS
R=OTs
R=OH
73
71
70
70
R =Cl
-1 V
0 V
1 V
2 V
aconditions: epoxide (0.05 M) in THF, 6 (10 mol%), 11 (1
mol%), 2 (2.0 eq.), r.t., 10 W blue LED. b 90:10 of 19 and product
with isopropylidene group. c10 mol% Cp2TiCl2. d84:16 mixture
of 1- and 2-dodecanol. e60 °C.
2+ 2
0.89
PC/PC- PC+/PC*
/
PC*/PC- PC+/PC
X=Cl X=TFA
-0.89 -0.57 -0.40
-1.37
1.21
1.69
The redox potentials (Scheme 2) show that 11* is able to
reduce both 5 and 6. However, 6 is more readily reduced
Scheme 2. Redox potentials of 2,8 5, 6, and complexes derived
from 11.9
than 5 (ΔE red = 0.17 V). Also, 6 is an efficient luminescence
½
quencher for 11* (for the Stern-Volmer plot, see Supporting
Information). We favor the oxidative quenching mechanism
(Scheme 1) because the redox potential difference (0.49 V,
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11+/11* and 6/6-) is more favorable than for the reductive
OH
Br
[PRCatn]*
quenching (0.32 V, 11*/11- and 2/2+)
1
2
3
PRCatn 11
N
R
=
Cp2TiCl2
With a powerful combination of catalysts in hands, we
decided to investigate the substrate scope of our process.
The reaction conditions can be applied successfully for
monosubstituted, cis-1,2 disubstituted, 1,1-disubstituted,
and trisubstituted epoxides. Several functional groups,
including the sensitive tosylate (entry 11), are tolerated.
The cyclobutane opening (entry 5) and the low
diastereoselectivity of the opening of 20 are indicative of
radical intermediates.
38
PRCatn+1
4
5
H
O[Ti]
Cp2TiCl
Br
O
Br
6
B'
N
R
Titanocene Cycle
7
8
9
N
R
PRCatn
37
[Ti] = Cp2TiIVCl
R= 4-Br-C6H4
PRCatn+1
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11
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O[Ti]
Br
H
An important aspect of the titanocene catalyzed epoxide
opening is the control of enantioselectivity of ring-
opening.10 To this end, Kagan’s complex 3611 has emerged
as the best precatalyst. Therefore, we investigated its
performance in the opening of 24 (Table 3). Without
additives a disappointingly low selectivity was obtained. In
the presence of Coll•HCl or LiCl, the enantioselectivity of
ring-opening improved significantly. DMPU as additive (1.5
eq. with respect to 24) gave even better results (entries 4
and 5). At a concentration of 0.17 M in THF for 24 an e.r. of
96:4 was observed.
O[Ti]
Br
N
R
N
R
A'
Scheme 3. Coupling of titanocene catalyzed radical arylation of
epoxides with PRC.
Indoline 38 was obtained in a yield of 80%. Thus, it is
clear that the coupling of the cycles is efficient (Table 4). The
typically employed strategy for the conversion of more
electron deficient substrates, the variation of the
titanocenes’ ligands is not necessary with PRC. Moreover,
the coupling of cycles also has a practical advantage. Simply
shining the light of a blue LED on a solution of two bench-
stable catalysts leads to the active catalytic system. No prior
reduction of Cp2TiCl2 is necessary.
Table 3. Enantioselective Opening of 24 with 36 and 11.
F3C
PF6
F
N
Ir
Table 4. Coupling of Ttitanocene Catalysis with PRC in
the Radical Arylation of Epoxides.
t-Bu
t-Bu
N
N
F
F
TiCl2
N
5
2-10 mol%
O
R4
2
OH
n
R4
F
11
1 mol%
F3C
n
0.05 M in THF, 65 o
blue LED
C
N
N
Kagan complex
R5
R5
11
36
OH
36
(10 mol%)
11
(1 mol%)
Br
OH
OH
O
OH
EtO
EtO
OEt
F3C
N
OEt
2
N
24
25
(S)-
additive,
N
blue LED
Br
entry
additive
none
(S) : (R)
66 : 34
86 : 14
89 : 11
90 : 10
96 :4
yield/[%]
5
5
5
4 mol% , 80%
2 mol% , 80%
4 mol% , 70%
1
2
60
55
56
55
60
38
39
OH
N
40
1.5 eq. Coll•HCl
1.5 eq. LiCl
OH
OH
3
F
N
4
5b
1.5 eq. DMPU
1.5 eq. DMPU
N
aconditions: epoxide (0.05 M in THF), 36 (10 mol%), 11 (1
5
5
5
6 mol% , 76%
4 mol% , 73%
10 mol% , 60%
mol%), 2 (2.0 eq), r.t., additive, two 10
W blue LED.
41
42
43
bconcentration of 24: 0.17 M in THF.
aconditions: epoxide (0.05 M in THF, Cp2TiCl2 (2-10 mol%), 11:
The second reaction investigated is the C-C bond forming
radical arylation reaction (Scheme 3).12 It is conceptually
related to the epoxide reduction by the Hantzsch ester 2
because the rate-determining step of the titanocene cycle is
the oxidation of the radical σ–complex A’ to B’. The use of
Cp2TiCl as sole catalyst results in the failure of the reaction
with 37. Only about 10% of 38 are formed due to the
inability of the pending Ti(IV) to oxidize radical σ–complex
A’ to B’. Therefore, we investigated if PRC with 11 can be
coupled with the radical arylation. The key features of this
approach are the generation of Cp2TiCl through reduction
1 mol%, 65 °C, two 10 W blue LED.
In summary, we have devised a new approach for
expanding the scope of catalytic radical reactions in single
electron steps. It relies on the merging of titanocene
catalysis with photoredox catalysis. The oxidation of radical
intermediates by the oxidized photoredox catalyst to
cations expands the scope of catalytic radical chemistry
because the titanocene(IV) intermediates are too weakly
oxidizing to accomplish this transformation. Sustainability
is increased by the generation of the active catalyst through
reduction by an excited photoredox catalyst from bench-
by [PRCatn]* and the oxidation of A’ to B’ by PRCatn+1
.
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ASSOCIATED CONTENT
Supporting Information.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: XXXXXXXXXXXXX
Experimental details and characterization data (PDF)
AUTHOR INFORMATION
Corresponding Author
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* andreas.gansaeuer@uni-bonn.de
Notes
The authors declare no competing financial interest..
ACKNOWLEDGMENT
We thank the Chinese Scholarship Council (Z. Z.) Konrad-
Adenauer-Stiftung
(R.
B.
R.),
the
Deutsche
Forschungsgemeinschaft (Ga 619/12-1).
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