Decarboxylative Hydroalkylation of Alkynes via Dual Copper-Photoredox Catalysis

Article abstract of DOI:10.1021/acscatal.0c01742

A photoredox strategy for the synthesis of a wide range of allylic amines and ethers from carboxylic acids and alkynes has been developed. This approach relies on the perturbation of the ground-state electronic properties of terminal alkynes through the formation and photoexcitation of copper acetylide intermediates. This process takes place through cooperative copper and organic photoredox catalysis and can be carried out in a stereodivergent manner. Thus, a systematic multivariate HTE screening spotlighted that a switch in the stereochemical outcome can be provoked by choosing an appropriate combination of ligand and base. The developed methodology has been applied to the stereoselective coupling of primary, secondary, and tertiary alkyl radicals with (hetero)aromatic terminal alkynes. As an additional practicality, similar reaction conditions allowed for the use of aromatic amines as radical precursors in a cross dehydrogenative coupling for the direct vinylation of inactivated C-H bonds.

Full text of DOI:10.1021/acscatal.0c01742

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Letter
Decarboxylative Hydroalkylation of Alkynes
via Dual Copper-Photoredox Catalysis
Marco M. Mastandrea, Santiago Cañellas, Xisco Caldentey, and Miquel A. Pericàs
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.0c01742 • Publication Date (Web): 20 May 2020
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ACS Catalysis
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Decarboxylative Hydroalkylation of Alkynes via Dual Copper-
Photoredox Catalysis
Marco M. Mastandrea,† Santiago Cañellas,†,§ Xisco Caldentey,† and Miquel A. Pericàs †,‡,
*
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† Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Instutite of Science and Technology (BIST). Avda.
Països Catalans 16, E-43007. Tarragona, Spain.
‡ Departament de Química Inorgànica i Orgànica. Universitat de Barcelona. Martí i Franqués 1-11, 08028. Barcelona, Spain
KEYWORDS: High-Throughput Experimentation • Photoredox catalysis • Hydroalkylation • Stereodivergent • Copper
catalysis.
ABSTRACT: A photoredox strategy for the synthesis of a wide range of allylic amines and ethers from carboxylic acids and alkynes
has been developed. This approach relies on the perturbation of the ground-state electronical properties of terminal alkynes through
the formation and photoexcitation of copper acetylide intermediates. This process takes place through cooperative copper and organic
photoredox catalysis and can be carried out in stereodivergent manner. Thus, a systematic multivariate HTE screening spotlighted
that a switch in the stereochemical outcome can be provoked by choosing an appropriate combination of ligand and base. The
developed methodology has been applied to the stereoselective coupling of primary, secondary and tertiary alkyl radicals with
(hetero)aromatic terminal alkynes. As an additional practicality, similar reaction conditions allowed for the use of aromatic amines
as radical precursors in a cross dehydrogenative coupling for the direct vinylation of inactivated C–H bonds.
Over the last decade, the resurgence of visible-light
photoredox catalysis has disclosed unprecedented opportunities
in the generation of radical intermediates by selective activation
of small organic molecules under mild reaction conditions.
These open-shell intermediates are often formed by a
photocatalyst mediated single-electron or by energy transfer
and engaged in peculiar reaction pathways which are
complementary to thermal two-electron processes.1
decarboxylative hydroalkylation of alkynes that takes
advantage of a migratory insertion step to afford terminal and
internal alkenes (Scheme 1b), while Wu proposed a Ni–H
catalyzed hydroalkylation of phenylacetylenes and enynes with
photocatalytically generated α-heteroatom radicals (Scheme
1c).
Scheme 1. Photoredox-catalyzed hydroalkylation of alkynes.6-9
a) Ir-catalyzed6
In this context, the radical additions to simple alkenes,
styrenes, and α,β-unsaturated carbonyl compounds have been
widely explored.2 In contrast and despite its attractiveness, the
reaction of radicals with alkynes has been less exploited.3 In
fact, alkynes are ubiquitous structural motifs and the ability of
a photocatalyst to perform selective energy transfer to them may
lay the foundations for unprecedented stereoselective
processes.4 From a mechanistic perspective, the reasons for the
limited development of radical addition to alkynes can be
probably assigned to the slow rate of C–C bond formation, this
being in turn related to the larger singlet-triplet gap of triple
bonds with respect to the corresponding double bonds.5
Nevertheless, Tang and co-workers have proposed an Ir-
catalyzed Z-selective synthesis of alkenes employing NHPI
O
Ar
[Ir]
Ar
O
N
Visible Light
O
O
b) Ir/Ni-catalyzed7,8
OH
R'
[Ir] + [Ni]
R'
Visible Light
R
R
Ar
O
c) Ir/Ni-catalyzed9
R
[Ir] + [Ni]
X
R
X
H
Visible Light
Ar
X = O, N-PG
d) This work
(Het)Ar
Cond. A
Cond. B
X
[4CzIPN] + [Cu]
(Het)Ar
OH
or
X
esters as radical sources, terminal arylalkynes and
a
Visible Light
O
superstoichiometric amount of DIPEA under visible light
irradiation (Scheme 1a).6 MacMillan,7 Rueping8 and Wu9
circumvented the aforementioned lack of reactivity adopting
multicatalytic approaches. Thus, MacMillan and Rueping
X = O, N-PG
X
(Het)Ar
Dual Cu/Photoredox Catalysis
HTE Screening
Stereodivergent Approach
Simple and Abundant Feedstocks
1º, 2º, and 3º Radicals
independently
developed
an
Ir/Ni
photocatalytic
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Ph
HTE screening
Ph
+
CO2H
N
N
1
2
3
4 ligands, 2 Cu sources,
4 solvents and 3 bases
Boc
Boc
Cz
Cz
1a
2a
3a
Cz:
NC
Cz
CN
Cz
4
5
N
6
4CzIPN
7
8
9
NH2
NH2
Ph
N
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L1
Boc
3a
Z-
NH2
Ph
NH2
N
Boc
3a
E-
L2
L3
Ph
N
N
2a
H2N
Other(s)
8
7
L4
Figure 1. Multivariate-HTE screening of solvents, bases, ligands and copper sources for the hydroalkylation of 2a under standard
conditions [1a (15 µmol), 2a (10 µmol), Base (20 µmol), Copper Source (2 µmol), Ligand (4 µmol if monodentate, 2 µmol if
bidentate), 4CzIPN (0.25 µmol), solvent (0.1 mL), blue LEDs irradiation, room temperature, 18 hours]. Yields (%) and (Z:E) ratios
[GC-FID analysis on the reaction crude using 1,1’-biphenyl as internal standard] for selected entries: A8: 79% (20:80), A9: 71%
(71:29), A12: 69% (25:75), E8: 73% (19:81), E9: 71% (63:39), E12: 71% (23:77).
Here we report a dual copper and photoredox catalyzed
decarboxylative hydroalkylation of alkynes leading to Z- or
E-enriched alkenes in a diastereodivergent manner from simple
carboxylic acids as radical sources10 and an organic
photocatalyst (Scheme 1d).
under these conditions with minimal erosion of the yield (entry
2, Table 1).
Table 1. Control experiments for the hydroalkylation of 2a.a
4CzIPN (2.5 mol%)
Ph
Cu(OAc)2 (20 mol%)
L1 (20 mol%)
Ph
Our approach to address this synthetic challenge is based on
the perturbation of the ground-state electronic properties of
terminal alkynes through the formation and photoexcitation of
the corresponding copper acetylides. The irradiation of copper
acetylides with visible light results in a ligand-to-metal charge
transfer (LMCT) increasing the electrophilicity on the alkyne
moiety.11 Hwang and coworkers, instead, exploited the ability
of such copper complexes to act as excited-state single-electron
reductants, and then be engaged in cross-coupling reactions and
functional group transformations.12
+
CO2H
N
N
Boc
CsOAc (2 equiv.), DMA
r.t., blue LEDs, 24 h
Boc
1a
2a
(Z)-3a (major)
Entry
Deviation from standarda
None
Yield (%)b
Z:Ec
78:22
23:77
1
2
82
72
L4 (40 mol%) instead of L1.
CsHCO3 instead of CsOAcd
3
4
5
6
7
8
No Cu(OAc)2
CuCl instead of Cu(OAc)2
No L1
19
78
58
0
78:22
77:23
69:31
n.d.
Considering all the variables involved in the designed
process, we considered
a multivariate high-throughput
experimentation (HTE) approach to screen the ligand, base,
copper source and solvent in a rapid and cost-effective manner
(Figure 1). We chose N-Boc Proline (1a) and phenylacetylene
(2a) as model substrates, and 4CzIPN13 as a photocatalyst. It
emerged that the best results in terms of yield and Z:E ratio were
achieved employing either CuOAc or Cu(OAc)2, (1R,2R)-
trans-1,2-diaminocyclohexane (L1) as ligand14 and CsOAc as
base under blue LEDs irradiation for 18 hours (wells A9 and
E9, Figure 1). Translation of the optimal conditions to
synthetically relevant scale allowed us to isolate the desired
product (3a) in 82% yield with a Z:E ratio of 78:22. Moreover,
the HTE screening also revealed that the reaction can be
performed in a diastereodivergent manner just by switching the
ligand and the base to oleylamine (L4) and CsHCO3 (wells A8
and E8, Figure 1), the E isomer being preferentially obtained
No photocatalyst
Dark
0
n.d.
3 mmol scale
76
67:33
aStandard conditions: 1a (0.3 mmol), 2a (0.2 mmol), CsOAc (0.4
mmol), DMA (2.0 mL), blue LEDs (4.5 W, Irradiation Setup 1).
bIsolated yield. Determined by GC-FID analysis on the reaction
c
crude. d36 hours, Irradiation Setup 2 (see SI for further details).
The choice of the ligand turned out to be key for the
stereoselectivity switch, since the combination of L4 and
CsOAc also provided 3a as an E-enriched product (wells A12
and E12, Figure 1). Control experiments showed that copper,
photocatalyst and light are fundamental for the reaction
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efficiency (entries 3, 4, 6 and 7, Table 1) and the nature of the
ligand is important for the selectivity of the transformation
(entries 2 and 5, Table 1). Interestingly, work at 3 mmol scale
(entry 8) is well tolerated.
phenylacetylide (2a’) is an active intermediate in the reaction.
To examine this hypothesis, we conducted the reaction under
the standard conditions replacing Cu(OAc)2 with 0.2 equiv. of
2a’ and reducing the amount of phenylacetylene to 0.8 equiv.
(Scheme 3a).
1
2
3
4
The scope of this transformation was next investigated under
the optimal reaction conditions (Figure 2). Sources of primary,
secondary, tertiary α-amino radicals as well as secondary α-oxy
radicals were tested in the Z-selective coupling. In all cases the
desired products were isolated in synthetically useful yields
ranging from moderate to good. It is worth mentioning that the
standard purification procedure by flash chromatography
affords in some instances completely separated Z:E
stereoisomers. These results have been highlighted in green in
Figure 2. For comparison purposes, the combined yield is also
given in these cases. As a general trend, a clear selectivity
towards the Z isomer is recorded except for the reactions in
which a quaternary carbon is formed: in these circumstances
(with the notable exception of 3j) the selectivity is reversed in
favor of the E isomer likely because of steric factors. In the two
cases where stereocenters with defined configuration were
already present in the carboxylic acids, the corresponding
products (3n and 3o) were isolated with very high
diastereoselectivity (3n >20:1; 3o >12:1). In the exploration of
the scope of the alkyne partner we first examined terminal
phenylacetylenes bearing electron withdrawing and electron
donating groups in ortho or para position. In the case of
electron-rich aromatic rings, a reverse stoichiometry of both
coupling partners was needed in order to achieve good yields.
Besides this, all products were obtained in good yields
regardless of the nature and position of the substituents (Figure
2). Also, more challenging heteroaromatic alkynes could be
employed in the reaction (4j-l) as well as an enyne (4m), albeit
the reaction took place in this case with moderate yield and E-
selectivity. Other non-conjugated alkynes (1-hexyne and tert-
butyldimethylsilylacetylene) turned out to be unsuitable
substrates for this transformation and failed to afford the
corresponding decarboxylative hydroalkylation products. We
then tested on selected substrates (3a, 3c, 4b and 4i) the
applicability of the stereo-complementary approach. Notably,
all of them were obtained in good yields and E-selectivities.
5
6
7
8
4CzIPN (2.5 mol%)
Cu(OAc)2 (20 mol%)
R4
R2 R3
H
R2 R3
L1 (20 mol%)
R1
R1
+
X
CO2H
X
CsOAc (2 equiv.), DMA, r.t.
4.5 W blue LEDs, 24 h
R4
X = N-PG, O
9
1
2
3-4 (Z:E)
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Carboxylic acid scopea,b
Ph
Ph
O
Ph
Ph
N
N
N
N
Boc
3d
Boc
Cbz
Boc
3a
3b
3c
75% (Z:E = 78:22)
52% (Z:E = 75:25)
82% (Z:E = 78/22)
72%(Z:E = 23/77)d
70% (Z:E = 76:24)
65% (Z:E = 15:85)d
Ph
Ph
Ph
Ph
HN
HN
Boc
3g
N
HN
Boc
Boc
Boc
3e
3f
3h
80% (Z:E = 75:25) 53% (Z:E = 72:28) 50% (Z:E = 72:28) 54% (Z:E = 78:22)
Ph
HN
Boc
Ph
HN
Boc
Ph
N
HN
Boc
Ph
Boc
3j
3i
3k
3l
24%(Z) + 47%(E) 45%(Z) + 27%(E)
28%(Z) + 43%(E)
65% (Z:E = 40:60)
(71% comb. yield) (72% comb. yield)
(71% comb. yield)
O
Ph
O
Ph
O
O
Ph
Ph
N
O
O
O
Boc
O
O
3o
3p
3m
3n
33% (Z:E = 77:23) 40% (Z:E = 67:34)
41% (Z:E = 69:31)
35%(Z) + 15%(E)
(50% comb. yield)
Alkyne scopea,b
R
Ph
Ph
4b, R=CF3 71% (Z:E = 73:27)
75% (Z:E = 26:74)d
4c, R=CN 56%(Z) + 27%(E) (83% comb. yield)
4d, R=OMe 55%(Z) + 17%(E) (72% comb. yield)c
4e, R=Me 75% (Z:E = 68:32)
HN
Boc
3q
62% (Z:E = 76:24)
4f, R=Cl 70% (Z:E = 76:24)
4g, R=CO2Me 59% (Z:E = 83:17)
N
Then, we tested the developed methodology in the direct
vinylation of inactivated C–H bonds. Upon single-electron
oxidation and deprotonation, aromatic amines generate the
corresponding α-amino radicals15 that could be trapped by the
excited copper acetylide complex thus forging a new C–C bond.
However, when we tested the feasibility of the transformation
using the optimized conditions to the cross dehydrogenative
coupling between 1r and 2a, we were unable to achieve
satisfactory results. Fortunately, a second HTE screening of
photocatalysts and bases (See SI for further details) revealed
that switching from 4CzIPN to [Ir(ppy)2(4,4’-dtbbpy)]PF6, the
formation of 3r could be achieved in good yield (75%) and high
Z-selectivity (82:18) (Scheme 2).
Boc
S
F
Me
N
N
N
Boc
4h
Boc
Boc
4i
4j
52% (Z:E = 85:15)
73% (Z:E = 60:40)c
79% (Z:E = 77:23)
65% (Z:E = 40:60)d
N
S
N
N
N
Boc
Boc
Boc
4k
73% (Z:E = 72:28)c
4l
4m
From a synthetic perspective, it is important to note that
simple stereoconvergent transformations of 3-4, such as the
selective hydrogenation of the double bond would result in
products formally arising from a very general decarboxylative
65% (Z:E = 84:16)
45% (Z:E = 48:52)
Figure 2. Carboxylic acid and alkyne scope in the
Copper/Photoredox catalyzed hydroalkylation of alkynes. All
yields shown refer to isolated products. aReactions performed with
carboxylic acid (0.3 mmol), alkyne (0.2 mmol), CsOAc (0.4
mmol), DMA (2.0 mL), blue LEDs (4.5 W). bZ:E ratios determined
by GC-FID on the reaction crude. Compounds isolated as pure
stereoisomers contained <1% of the alternative geometrical isomer.
cReactions performed with carboxylic acid (0.2 mmol), alkyne (0.7
hydroxyalkylation of alkenes,
a process being actively
developed these days.16
Next, we performed a series of experiments aimed at
shedding light on key mechanistic aspects of this
transformation. First, we questioned whether Cu(I)
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Page 4 of 7
mmol). dResults in boldface refer to reaction conditions favoring E
selectivity: L4 (40 mol%) instead of L1, CsHCO3 instead of
CsOAc.
Ph
a)
Ph
Standard conditions
H1(D1)
1
2
+
CO2H
N
N
D2O (X equiv.)
Anhydrous DMA
H2(D2)
Boc
Boc
3
4
Scheme 2. Cross dehydrogenative coupling between 1q and 2a
1a
2a
3a
allowing the vinylation of inactivated C-H bonds.
5
6
Ph
7
8
9
Ph
Standard conditions
+
N
N
Ph
[Ir(ppy)2(4,4'-dtbbpy)]PF6 (0.5 mol%)
instead of 4CzIPN
Ph
1r
2a
3r
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11
12
13
14
15
16
17
18
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20
21
22
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59
60
61%(Z) + 14%(E)
(75% combined yield)
The corresponding product 3a was obtained in similar yield
and Z-selectivity, supporting the intermediacy of Cu(I)-
phenylacetylide. On the other hand, the addition of TEMPO (1
equiv.) completely quenches the reaction (Scheme 3b) and
yields 3a’ indicating the involvement of α-amino/oxy radical
intermediates in the transformation. Then, an E-enriched
mixture of 3a (0.1 M in DMA) was irradiated for 24 hours in
the presence of 4CzIPN (2.5 mol%) being isomerized to the
same Z:E value of the model reaction. This experiment suggests
that the E/Z selectivity of the reaction arises from an energy
transfer process mediated by the photocatalyst (Scheme 3c).
The same result was obtained adding L4 (40 mol%) to the
mixture, excluding that the E selectivity arises from quenching
of the triplet state of 4CzIPN exerted by the double bond present
in the ligand.
Ph
b)
Ph
Standard conditions
H1(D1)
+
CO2H
N
N
a) DMF-d7
b) CD3C(O)NEt2
a) or b) instead of DMA
H2(D2)
Boc
Boc
1a
2a
3a
a) 65% (0% D)
b) 56% (0% D)
Scheme 5. Proposed reaction mechanism.
Scheme 3. Mechanistic experiments.
Ph
a)
Ph
Standard conditions
+
+
CO2H
N
N
Cu(I)
2a'
Ph
Boc
Boc
(0.2 equiv.)
2a
1a
3a
[81% (72:28)]
(0.8 equiv.)
instead of Cu(OAc)2
b)
Ph
Standard conditions
N
O
CO2H
N
N
TEMPO (1 equiv.)
Boc
Boc
1a
2a
3a'
(30% yield)
Ph
c)
4CzIPN (2.5 mol%)
DMA (0.1 M), r.t.
Ph
N
N
Boc
3a
Boc
24 h, 4.5 W blue LEDs
3a
3a
(Z/E 79:21)
(Z/E 77:23 with 40 mol%
(Z/E 36:64)
L4
)
Finally, we investigated the source of vinylic hydrogens in
the final product and consequently the process involved in their
incorporation. To do so, we designed experiments choosing
deuterated compounds able to exchange deuterium via a polar
or a radical process (deuterium atom abstraction). We selected
deuterium oxide as deuterons exchanger and performed the
model reaction adding increasing amounts of D2O. These
experiments show that there is a correlation between the amount
of D2O and the incorporation of deuterium in both positions of
the double bond (Scheme 4, a). On the other hand, experiments
using other deuterated solvents such as DMF-d7 and N,N-
diethylacetamide-d3 (chosen as deuterium atoms donors)
furnished the desired product with no significant deuterium
incorporation (Scheme 4, b).
Taking all these results into account, the tentative
mechanistic proposal shown in Scheme 5 was formulated. Upon
irradiation, the photocatalyst 4CzIPN can reach its excited state
PC* (E1/2 PC·+/PC* = -1.04 V vs SCE and E1/2 PC*/PC·−
=
+1.35 V vs SCE)11 and it is able to reduce the Cu(II) complexes
present in solution (e.g., E1/2 Cu(II)/Cu(I) = -0.363 V vs SCE
for [Cu(L1)2](ClO4)2)15,17,18 as well as to oxidize α-amino and
ox
α-oxy carboxylates (e.g., Boc-Pro-OCs, E1/2 = +0.95 V vs
SCE).19 Stern-Volmer studies indicates that the reductive
quenching of the catalyst exerted by the Boc-Pro-OCs is faster
(KSV = 2.9·10-2 M-1) than the one exerted by [Cu(L1)2](OAc)2
(KSV = 1.4·10-2 M-1).20 The Cu(I) complex generated either by
disproportionation of the Cu(II) source or SET by PC* (or PC·−
[PC/PC·− = -1.21 V vs SCE]) can form complex A (the
structure of A might be either a monomeric or a polymeric form
or both) with the assistance of a base (CsOAc).21 Direct
Scheme 4. Deuterium labelling experiments.
photoexcitation of
A
(λabs
=
476 nm for Cu(I)
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phenylacetylide)12f to A* could determine a depletion of charge
on the alkyne moiety through ligand-to-metal charge transfer
(LMCT), accelerating the attack of the radical E (formed upon
deprotonation and single electron oxidation of D either by PC*
or PC·+ [PC·+/PC = +1.52 V vs SCE]). This addition results in
the formation of the vinyl radical B which forms the
corresponding vinyl anion C oxidizing PC·−. Anion protonation
and proto-demetallation of the Cu–C bond afford the desired
product 3a, regenerating the Cu(I) species. Taking into account
the outcome of the E-selective methodology, and the control
experiment previously shown, it is reasonable to assume that
the product is formed as an E-enriched mixture and then is
isomerized via energy transfer (ET (4CzIPN) = 60 kcal·mol-1)22
mediated by the photocatalyst.
6828-6838; (c) Reckenthäler, M.; Griesbeck, A. G. Photoredox
catalysis for organic syntheses. Adv. Synth. Catal. 2013, 355, 2727-
2744; (d) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Visible light
photoredox catalysis with transition metal complexes: applications in
organic synthesis. Chem. Rev. 2013, 113, 5322-5363; (e) Schultz, D.
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Group for Conjugate Additions: A Three-Step Synthesis of (±)-
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A. G.; Malinowski, J. T.; McAlpine, N. J.; Kuhne, J.; MacMillan, D.
W. C. Direct, enantioselective -alkylation of aldehydes using simple
olefins. Nat. Chem. 2017, 9, 1073-1077; (e) El Marrouni, A.; Rittsband,
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In summary, we have developed a catalytic method for
intermolecular hydroalkylation of terminal alkynes with
carboxylic acids. The use of a widely available and stable
copper-based catalyst allows the overcoming of the intrinsic
kinetic barrier associated with the addition of radicals to triple
bonds. At the same time, this transformation exploits the ability
of an organic photocatalyst to generate alkyl radicals from in
situ generated carboxylates and isomerize the formed alkene to
the less stable Z isomer. In this work, HTE screening of reaction
conditions revealed that the proper choice of copper ligand and
base makes possible the selective shutdown of the latter process
without compromising the efficiency of the former thereby
paving the way to the stereodivergency of the reaction. These
aspects, along with the low cost and abundance of the starting
materials as well as catalysts, suggest that this synthetic
Gao, Y.; Zhou, C.; Li, G.
Visible-Light-Driven Reductive
methodology
can
complement
other
photoredox
Carboarylation of Styrenes with CO2 and Aryl Halides. J. Am. Chem.
Soc. 2020, 142, 8122-8129.
hydroalkylation reactions of alkynes relying upon the use of
iridium catalysts and PR functionalized substrates.
(3) Light-initiated radical additions to triple bonds are mostly
restricted to internal alkynes. For a review, see; (a) Huang, M.-H. Hao,
W.-J. Li, G.; Tu, S.-J.; Jiang, B. Recent advances in radical
transformations of internal alkynes. Chem. Commun. 2018, 54, 10791-
10811. For some recent examples, see: (b) Feng, S.; Xie, X.; Zhang,
W.; Liu, L.; Zhong, Z.; Xu, D.; She, X. Visible-Light-Promoted Dual
AUTHOR INFORMATION
Corresponding Author
* E-mail for M.A.P.: mapericas@iciq.es.
C−C Bond Formations of Alkynoates via
a Domino Radical
Present Addresses
Addition/Cyclization Reaction: A Synthesis of Coumarins. Org. Lett.
2016, 18, 3846-3849; (c) Han, H. S.; Lee, Y. J.; Jung, Y.-S.; Han, S. B.
Stereoselective Photoredox-Catalyzed Chlorotrifluoromethylation of
Alkynes: Synthesis of Tetrasubstituted Alkenes. Org. Lett. 2017, 19,
1962-1965; (d) Liang, H.; Ji, Y.-X.; Wang, R.-H.; Zhang, Z. H.; Zhang,
§ S. C.: Discovery Sciences, Janssen Research and Development.
Janssen-Cilag, S.A. Jarama 75A, 45007, Toledo (Spain).
Notes
The authors declare no competing financial interest.
B.
Visible-Light-Initiated
Manganese-Catalyzed
E‑Selective
Hydrosilylation and Hydrogermylation of Alkynes. Org. Lett. 2019, 21,
2750−2754; (e) Rai, P.; Maji, K.; Maji B. Photoredox/Cobalt Dual
Catalysis for Visible-Light-Mediated Alkene−Alkyne Coupling. Org.
Lett. 2019, 21, 3755-3759: (f) Zhang, Y.; Xu, J.; Guo, H. Light-Induced
Intramolecular Iodine-Atom Transfer Radical Addition of Alkyne: An
Approach from Aryl Iodide to Alkenyl Iodide. Org. Lett. 2019, 21,
9133−9137. For some examples involving additions to terminal
alkynes, see: (g) Wang, X.; Studer, A. Regio- and Stereoselective
ASSOCIATED CONTENT
Supporting Information. The Supporting Information is available
free of charge on the ACS Publications website at
http://pubs.acs.org.
Experimental procedures and spectral data (PDF)
ACKNOWLEDGMENT
Radical
Perfluoroalkyltriflation
of
Alkynes
Using
This work is dedicated to our colleague and friend, Prof. Kilian
Muñiz, in memoriam, and was funded by MINECO/FEDER (grants
CTQ2015-69136-R and PID2019-109236RB-I00) and the CERCA
Program/Generalitat de Catalunya. We thank the CELLEX
Foundation for funding the CELLEX-ICIQ High Throughput
Experimentation (HTE) platform. S. C. thanks the MINECO for a
Severo Ochoa FPI fellowship (BES-2015-072152).
Phenyl(perfluoroalkyl)iodonium Triflates. Org. Lett. 2017, 19,
2977−2980; (h) Guo, L.; Song, F.; Zhu, S.; Li, H.; Chu L. Syn-Selective
alkylarylation of terminal alkynes via the combination of photoredox
and nickel catalysis. Nat. Commun 2018, 9:4543; (i) Chalotra, N.;
Ahmed, A.; Rizvi, M. A.; Hussain, Z.; Ahmed, Q. N.; Shah, B. A.
Photoredox Generated Vinyl Radicals: Synthesis of Bisindoles and
β‑Carbolines. J. Org. Chem. 2018, 83, 14443-14456; (j) Alkan-
Zambada, M.; Hu, X. Cu-Catalyzed Photoredox Chlorosulfonation of
Alkenes and Alkynes. J. Org. Chem. 2019, 84, 4525−4533.
(4) For a review, see: Strieth-Kalthoff, F.; James, M. J.; Teders, M.;
Pitzer, L.; Glorius, F. Energy transfer catalysis mediated by visible
light: principles, applications, directions. Chem. Soc. Rev. 2018, 47,
7190-7202.
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11b and 11c.
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(20) See SI, Section 2e.
(21) A can also be formed in presence of Cu(I) species under visible
light irradiation without the assistance of a base, see reference 7f.
(22) Lu, J.; Pattengale, B.; Liu, Q.; Yang, S.; Shi, W.; Li, S.; Huang,
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Synopsis TOC (if needed)
A dual copper and organic photoredox catalysis approach for the synthesis of allylic amines and ethers from carboxylic acids and alkynes has been
developed. This approach relies on the perturbation of the ground-state electronical properties of terminal alkynes via visible-light excitation of
copper acetylide intermediates. HTE spotlighted the stereodivergency of this reaction by choosing an appropriate combination of ligand and base.
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