8-Mercaptoquinoline as a Ligand for Enhancing the Photocatalytic Activity of Pt(II) Coordination Complexes: Reactions and Mechanistic Insights

Article abstract of DOI:10.1021/acs.joc.9b00520

A family of quinoline-platinum(II) complexes as efficient photocatalysts is presented. Their key characteristic is their easy preparation by coordination of the readily available 8-hydroxy- or 8-thio-quinoline ligands, which are well known for their strong chelating ability to different metal ions. In the different photochemical transformations investigated, such as cross-dehydrogenative coupling, oxidation of arylboronic acids, and asymmetric alkylation of aldehydes, 8-mercaptoquinoline-Pt(II) complex proved to be the most general catalyst. Moreover, quenching experiments showed that, contrary to related methods reported in the literature, these complexes followed an oxidative quenching mechanism in all transformations studied. Besides, simulations performed with high-level ab initio methods of the complexes have helped to understand their photocatalytic activity.

Full text of DOI:10.1021/acs.joc.9b00520

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Article
8-Mercaptoquinoline as Ligand for Enhancing the Photocatalytic Activity
of Pt(II) Coordination Complexes: Reactions and Mechanistic Insights
Antonio Casado-Sánchez, Mustafa Uygur, Daniel González-Muñoz, Fernando
Aguilar-Galindo, José Luis Nova-Fernández, Judith Arranz-Plaza, Sergio
Díaz-Tendero, Silvia Cabrera, Olga Garcia Mancheno, and José Alemán
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00520 • Publication Date (Web): 18 Apr 2019
Downloaded from http://pubs.acs.org on April 18, 2019
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8-Mercaptoquinoline as Ligand for Enhancing the
Photocatalytic Activity of Pt(II) Coordination
Complexes: Reactions and Mechanistic Insights
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Antonio Casado-Sánchez,a Mustafa Uygur,b Daniel González-Muñoz,a Fernando Aguilar-
Galindo,c José Luis Nova-Fernández,d Judith Arranz-Plaza,d Sergio Díaz-Tendero,c,e,f Silvia
Cabrera,*d,f Olga García Mancheño,*b and José Alemán*a,f
a Organic Chemistry Department, Universidad Autónoma de Madrid, 28049 Madrid (Spain)
b Organic Chemistry Department, University of Münster, 48149 Münster (Germany)
c Chemistry Department, Universidad Autónoma de Madrid, 28049 Madrid (Spain)
d Inorganic Chemistry Department, Universidad Autónoma de Madrid, 28049 Madrid (Spain)
e Condensed Matter Physics (IFIMAC), Universidad Autónoma de Madrid, 28049 Madrid (Spain)
f
Institute for Advanced Research in Chemical Sciences (IAdChem), Universidad Autónoma de
Madrid, 28049 Madrid (Spain).
KEYWORDS: Photocatalysis• Platinum complex• Thioquinoline ligand • CASPT2 calculations
• Mechanism
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ABSTRACT. A family of quinoline-platinum(II) complexes as efficient photocatalysts is
presented. Their key characteristic is their easy preparation by coordination of the readily available
8-hydroxy- or 8-thio-quinolines ligands, which are well known for their strong chelating ability to
different metal ions. In the different photochemical transformations investigated, such as cross-
dehydrogenative couplings, oxidation of aryl boronic acids and asymmetric alkylations of
aldehydes, the 8-mercaptoquinoline-Pt(II) complex proved to be the most general catalyst.
Moreover, quenching experiments showed that, contrary to related methods reported in the
literature, these complexes followed an oxidative quenching mechanism in all the transformations
studied. Besides, simulations performed with high-level ab initio methods of the complexes have
helped to understand their photocatalytic activity.
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INTRODUCTION
Visible-light photocatalysis has become a powerful tool for the formation of new bonds and
molecules, using smooth and mild reaction conditions.1 In recent years, most of the organic
synthetic transformations have been carried out using organic dyes such as eosin Y or flavin,2 and
transition metals such as Ru(II) and Ir(III) complexes as photocatalysts.3 Despite the rich
photochemical and photophysical properties of many metallic complexes, their application as
catalysts in light-mediated organic transformations has focused mainly on the aforementioned
ruthenium and iridium complexes.4 For example, cyclometalated platinum(II) complexes, which
are known to be highly luminescent, have been widely studied as organic-light emitting diodes
(OLEDs),5 but scarcely applied as photocatalysts in spite of their rich photophysical properties. In
fact, the use of platinum(II) complexes as photocatalysts in organic transformations is reduced to
organometallic complexes (I-III, Figure 1).6 These complexes I-III have been used successfully
for different reactions, but they present some drawbacks related to their preparation: i) their
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synthesis requires a large number of steps and only low overall yields are obtained; ii) each
complex contains two different ligands that are not commercially available (usually 3-5 synthetic
step/ligand); iii) Schlenk techniques are required. Therefore, to optimize each reaction different
organometallic platinum complexes must be synthesized, which is a lengthy and time-consuming
process. It would be highly desirable to find an easy synthesis and a fine-tuning platinum
photocatalyst for broader applications.
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The coordination of simple and commercially available 8-hydroxy- or 8-thio-quinoline
ligands to platinum, which are known as non-innocent ligands,7 would modify the photophysical
and redox properties of complexes in a very easy manner. Sulfur based ligands have been used
with different metals such as Cu, Pd, Pt or Rh, especially in the field of transition metal catalysis
for the improvement of their catalytic performances.8 However, this type of ligand has been less
explored in the photocatalytic area. In 2016, we reported that platinum(II) complexes (Y= O,
Figure 1) bearing 8-hydroxyquinoline ligands9 were excellent photocatalysts for the oxidation of
sulfides in both batch and under flow reaction conditions.10 We wondered if the substitution of the
hydroxyquinoline by a thioquinoline ligand has any influence in photocatalytic activity of three
different reactions. In this work, we present the application of mercapto-quinoline platinum(II)
complex (Y= S, Figure 1) to a variety of photocatalytic reactions such as the aerobic Cross-
Dehydrogenative-Coupling (CDC), the oxidation of boronic acids, and the dual-catalyzed
asymmetric alkylation of aldehydes. We also analyzed the higher catalytic performance of the thio-
platinum(II) complex compared to that of the hydroxyl-analogue. In addition, high-level ab initio
calculations of the singlet and triplet excited states of the platinum complexes, and different
mechanistic proofs have been performed to explain the better catalytic activity of this sulfur-
platinum complex.
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Previously described Pt(II) photocatalysts: Organometallic complexes
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MeO
OMe
tBu
tBu
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N
N
N
N
Pt
N
Pt
Ph2P
Pt
N
N
PPh2
F
F
F
F
F
II
III
Multi-Step Synthesis of Ligands and Complexes
Difficult Photocatalytic Modulation
Schlenk Technique Synthesis
I
This work: Pt(II): Coordination Complex
better S than O?
Commercially Available Ligands
One Step Synthesis
Straightforward Photocatalytic Modulation
Air Compatible Synthesis
N
Y
Pt
dmso
Cl
1 Y
( = S, O)
Reactions Studied
N
LIGHT
Nu
Ar
N
Ar
Nu
Ar OH
N
Ar B(OH)2
S
Pt
dmso
Cl
O
O
R'
R'
H
H
Br
R
R
Figure 1. Selected platinum(II) photocatalysts previously described and our family of
photocatalysts.
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RESULTS AND DISCUSSION
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Photocatalytic Cross-Dehydrogenative-Coupling. The C-H bond cross-dehydrogenative-
coupling reaction represents a potent method to construct C-C and C-heteroatom bonds under
oxidative conditions, avoiding pre-functionalization and defunctionalization steps on the
substrates.11 In this type of chemistry, the choice of the appropriate oxidant for each targeted
reaction is crucial for its success.11,12 During the past few years, the functionalization of C-H bonds
using visible light photoredox catalysis has emerged as a powerful approach for the efficient
synthesis of organic molecules under mild, atom-economic and environmental friendly
conditions.13 In this context, the direct C(sp3)-H functionalization of heterocycles represents an
important synthetic transformation towards a broad variety of biologically active compounds.11,14
First, Stephenson reported the oxidative coupling of tetrahydroisoquinolines (THIQs) with
nitroalkanes under visible-light catalysis, using an iridium-based catalyst.15 As an alternative, other
groups have developed metal-free, visible-light-mediated oxidative C(sp3)-H coupling reactions,16
as well as dual catalytic systems combining photoredox with H-donor and Lewis base catalysis17
or N-heterocyclic carbene catalysis.18
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With these precedents in mind we wondered if our family of platinum(II) complexes would
be able to effectively catalyze the CDC reaction of THIQs with different nucleophiles. Therefore,
the oxidative coupling of N-phenyl THIQ (2a) with dimethylmalonate (3a) in the presence of
catalyst 1, blue light (3W blue LED) and air atmosphere was evaluated as a model reaction (Table
1).
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Table 1. Optimization of reaction conditions and catalyst for the photocatalytic Cross-
Dehydrogenative-Coupling of 2a.a
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1a
1b
(Y= S)
(Y= O)
N
Y
Pt
dmso
Cl
N
N
Ph
Ph
MeO2C
CO2Me
3a
MeO2C
4aa
CO2Me
blue LEDs, air
2a
solvent, 24 h, rt
Entry
1c
Catalyst 1
Solvent
Conversion (%)b
--
MeCN
MeCN
10
>98 (>98)e
>98 (80)e
>98
2c
1a
1b
1a
1a
1a
1a
1a
1a
1a
3c
MeCN
4d
MeCN
5d
EtOH
92
6d
Toluene
92
7d
MeCN:H2O (1:1)
Tol:H2O (1:1)
MeCN
59
8d
30
9f
17
10g
MeCN
98h
a Conditions: 2a (0.2 mmol), catalyst 1 (1 mol %) and malonate 3a (0.24 mmol, 1.2
eq.) were dissolved in dry acetonitrile (0.1 M). b Conversion measured by 1H-NMR.
c
d
Reaction using a glass-finger system open to the air (blue LED, 3W). Reaction
e
using a vial with a septum open to the air with a needle (blue LEDs, 15W).
f
Conversion after 18 h in parentheses. Following conditions d but under N2-
g
atmosphere. Following conditions d but the system was initially bubbled with O2
(5 min) and kept under an O2-atmosphere (1 atm, balloon). h Conversion after 8 h.
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Firstly, the reaction that was carried out in the absence of the catalyst proceeded with only a
very low conversion, which confirmed the essential role of the photocatalyst in our reaction
conditions (entry 1, Table 1). Conversely, using any of the two platinum(II) complexes 1 the
reaction proceeded with full conversion after 24 h (entries 2-3). However, among them, the
mercapto-catalyst 1a was the most active after 18 h (see results between parentheses). Having
identified 1a as the best catalyst, different solvents in a more powerful irradiation system (15W
blue LED) were screened (entries 4-8). Toluene and acetonitrile were the most effective, while the
presence of water had a negative effect and decreased the conversion of the reaction. In addition,
as anticipated the reaction performed under a nitrogen atmosphere was unsuccessful (entry 9),
while the reaction carried out under an O2 atmosphere achieved a full conversion in only 8 h (entry
10).
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Once the optimal conditions were determined, we proceeded to study the scope of the reaction
with different nucleophiles using the catalyst 1a (Table 2). The reaction tolerated the introduction
of nitrile, nitro and phosphite derivatives, affording the corresponding products 4ab-4ad in good
yields. Moreover, the PMP-protected derivative 2b was also used for the functionalization with
methyl and ethyl malonate (3a and 3e) and potassium allyltrifluoroborate (3f) to give 4ba, 4be and
4bf. Lastly, the intramolecular version of this reaction worked well, allowing the synthesis of the
fused derivatives 4c and 4d in 58 and 78% yield, respectively.
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Table 2. Scope in the 1a-photocatalyzed Cross-Dehydrogenative-Coupling of THIQs 2.a
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N
S
Pt
dmso
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Cl
(1 mol%)
N
+
Nu
3
N
blue LEDs (15W), O2
8-24 h, CH3CN, rt
Ar
Ar
Nu
4
2
N
N
N
Ph
Ph
Ph
CN
MeO2C
CO2Me
NO2
4ac
, 53% Yield
4aa
, 48% Yield
4ab
, 52% Yield
N
N
N
PMP
CO2Et
, 61% Yield
PMP
Ph
PO(OEt)2
EtO2C
4be
MeO2C
4ba
CO2Me
b
4ad
, 82% Yield
, 46% Yield
N
N
N
PMP
Cl
O
O
4bf
, 47% Yield
4c
, 58% Yield
4d
, 78% Yield
a Conditions: 2 (0.2 mmol), catalyst 1a (1 mol%) and nucleophile 3 (0.24
mmol, 1.2 equiv.) were dissolved in dry acetonitrile (0.1 M). Reaction was
initially bubbled with O2 (5 min) and kept under an O2-atmosphere (1 atm,
balloon), using a vial with a septum (blue LEDs, 15W). Isolated yields. b
Reaction with (EtO)3P in toluene/H2O (1:1) under air using 5 mol% of 1a.
Photocatalytic Oxidation of Boronic Acids. The oxidation of arylboronic acid derivatives with
peroxides under basic conditions is one of the most efficient methodologies to access their
corresponding phenols, which are important natural and bioactive compounds.19 However, the use
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of peroxides as oxidants in industrial processes is undesirable due to the safety issues associated
with their handling. Therefore, the photo-oxidation of arylboronic acids using atmospheric O2
would be a safer alternative.20 In this section, the oxidation of arylboronic acids using the platinum
complexes 1 was evaluated (Tables 3 and 4).
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The optimization of the reaction with phenylboronic acid began with the investigation of
different platinum complexes 1 (Table 3). This revealed that the best photocatalyst was again the
mercapto catalyst 1a, which afforded full conversion in 48 h (entries 1-3). Next, the reaction time
was shortened to 24 h and the catalyst loading was decreased to 2 mol% for the screening of the
solvent (entries 4-9) and amine (entries 5, 10-11). Under these reaction conditions, DMF gave the
highest yield (56% yield, entry 4), which was increased to 70% using Et3N instead of DIPEA as
the sacrificial electron donor (entry 10). Finally, the evaluation of the irradiation source (entries
12-14) showed that the white LED was the most appropriate, leading to the phenol product (6a) in
an excellent yield (91%). Unfortunately, lowering further the amount of catalyst to 1 mol%
substantially decreased the yield of the oxidation (entry 15).
Table 3. Optimization of reaction conditions for the oxidation of phenylboronic acid.a
1a
1b
(Y= S)
(Y= O)
N
B(OH)2
Y
OH
Pt
dmso
Cl
amine, light, DMF
air, rt
5a
6a
Yield
(%)b
Entry 1 (mol%)
Amine (light)
Solvent
Time (h)
1
2
--
DIPEA (CFL)
DIPEA (CFL)
DMF
DMF
24
48
n.r.
90
1a (5)
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1b (5)
1a (2)
1a (2)
1a (2)
1a (2)
1a (2)
1a (2)
1a (2)
1a (2)
1a (2)
1a (2)
1a (2)
1a (1)
DIPEA (CFL)
DIPEA (CFL)
DIPEA (CFL)
DIPEA (CFL)
DIPEA (CFL)
DIPEA (CFL)
DIPEA (CFL)
Et3N (CFL)
DMF
DMF
48
24
24
24
24
24
24
24
24
24
24
24
24
41
56
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5
MeCN
Toluene
DCM
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7
8
EtOH
9
EtOH/H2O
DMF
3
10
11
12
13
14
15
70
7
CH3N(Ph)2 (CFL)
Et3N (green LED)
Et3N (blue LED)
Et3N (white LED)
Et3N (white LED)
DMF
DMF
34
74
91
79
DMF
DMF
DMF
a
Conditions: 5a (0.10 mmol), amine (0.11 mmol) and catalyst 1 (x mol%) were
dissolved in the corresponding solvent (0.05 M) under the irradiation system
indicated. b NMR-yield determined using MeNO2 as the internal standard.
With the optimized reaction conditions established, the scope of the reaction was explored
(Table 4). The transformation worked smoothly with arylboronic acids bearing weakly activating
groups such as methyl (6b and 6c) or with strong EDG and EWGs such as 4-MeO, CF3 or CN (6d-
6f), leading to the products in good yields (60-89%). The presence of a chlorine atom at the aryl
group (6g) and heteroaryl moieties (6h) was also compatible with the photo-oxidation conditions,
obtaining the corresponding phenols in moderate to good yields (48-70%).
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Table 4. Scope of oxidation of arylboronic acids under 1a catalyst.a
5
6
7
8
9
N
S
Pt
dmso
1a
Cl
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11
12
13
14
15
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Et3N (1.1 equiv.)
B(OH)2
Ar OH
Ar
DMF , white LED
air, rt, 24-48 h
5
6
OH
OH
OH
OH
OMe
b
b
b
6a
, 91% Yield 6b
6c
, 60% Yield
OH
, 70% Yield
OH
6d
, 89% Yield
OH
HO
N
H
F3C
CF3
Cl
CN
b
b
6g
6h
, 48% Yield
, 70% Yield
6f
, 88% Yield
6e
, 81% Yield
a Conditions: 5 (0.10 mmol), Et3N (0.11 mmol) and catalyst
1a (2 mol%) were dissolved in DMF (0.05 M) under white
LEDs. Yields determined after flash chromatography.
b
NMR-yield determined using MeNO2 as internal standard.
Photocatalytic Asymmetric -Alkylation of Aldehydes. In the previous sections, we have
shown that platinum(II) complexes can be used in photo-oxidation reactions. In order to
demonstrate the general application of our photocatalysts, the platinum(II) complexes were tested
in a more complex reaction: the asymmetric -functionalization of aldehydes with bromo
derivatives. The asymmetric -alkylation of aldehydes and ketones has become an attractive
reaction due to the synthetic utility of the final products obtained. In 2008 MacMillan and co-
workers found an extraordinary example in which the combination of an imidazolidinone
2+
organocatalyst and the photoredox catalyst Ru(bpy)3 enabled the asymmetric -alkylation of
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aldehydes, starting from alkyl-bromo derivatives.21 Since then, different catalytic systems that
combine a photocatalytic counterpart with an imidazolidinone organocatalyst have also been
reported.22 However, to the best of our knowledge this study represents the first platinum(II) co-
catalyzed asymmetric -alkylation of aldehydes.
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To evaluate our photocatalysts in this transformation, the aldehyde 7a, bromomalonate 8a and
the MacMillan catalyst 9a were initially used in the presence of photocatalysts 1a-b under visible-
light irradiation (Table 5). Surprisingly, the reaction only proceeded with photocatalyst 1a,
obtaining null conversion in the case of the platinum complex 1b (entries 1-2). Moreover, the
change to the bulkier amino organocatalyst 9b slightly increased the enantioselectivity to 92%
(entry 3). To our delight, the use of a blue LED photoreactor system gave full conversion and an
outstanding 96% ee (entry 4), better than either the green or white light (entries 5 and 6). Other
solvents such as DMSO or CH3CN provided lower conversions (entries 7-8). As we have
previously demonstrated,22d the reaction did not proceed without catalyst 1, being the
aminocatalyst 9b unable to promote the -alkylation of aldehydes without an external
photocatalyst (entry 9).
Under the optimized reaction conditions (entry 4, Table 5), the alkylation reaction was then
explored using different aldehydes and organic bromides (Table 6). As a result, various aldehydes
7 bearing pendant alkylic, arylic and heterocyclic groups were efficiently -alkylated with diethyl
bromomalonate (8a) and bromoacetophenone (8b), leading to the products 10a-d in good to
excellent yields (47-91%) and enantioselectivities (84-96% ee). This study validates the
compatibility of the platinum(II) photocatalyst with organocatalysis and more importantly, its
broad application in photoredox processes.
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Table 5. Optimization of reaction conditions for the -alkylation of aldehydes.a
5
6
7
8
O
CO2Et
CO2Et
O
1a-b
9a-b
(20 mol%)
(2 mol%),
EtO2C
CO2Et
H
H
+
2,6-lutidine, Solvent, Light
N2 atmosphere, rt, 24h
Br
8a
9
5
5
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7a
10a
O
N
O
N
tBu
Me
Ph
N
N
tBu
N
N
H
H
S
O
Pt
Pt
dmso
dmso
Cl
Cl
1a
1b
9a
9b
Entry
1
9
Solvent
Light
Conversion
(%)b
ee (%)c
1
2
3
4
5
6
7
8
9
1a 9a
1b 9a
1a 9b
1a 9b
1a 9b
1a 9b
1a 9b
1a 9b
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
MeCN
DMF
CFL (15W)
CFL (15W)
CFL (15W)
Blue LED
Green LED
White LED
Blue LED
Blue LED
Blue LED
42
n.r.
28
90
-
92
96
95
94
95
96
-
>98
95
60
50
62
-
9b
<5
a Conditions: 7a (0.20 mmol), 8a (0.10 mmol), 1 (2 mol%), 9 (20 mol%) and 2,6-lutidine
(0.36 mmol) were dissolved in the solvent indicated (0.6 M) under nitrogen atmosphere
and the irradiation system indicated. Conversions determined by H-NMR. ee
b
1
c
determined by SFC-LC using chiral columns.
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Table 6. Scope of the asymmetric alkylation of aldehydes 7 with bromo derivatives 8.a
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6
7
8
O
O
1a
9b
(20 mol%)
(2 mol%),
R´
R´
Br
H
H
2,6-lutidine, DMF,
R
R
9
N2 atmosphere, rt, 24 h
blue LED
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7
8
10
O
CO2Et
O
O
CO2Et
CO2Et
O
CO2Et
CO2Et
Ph
H
CO2Et
H
H
H
O
Ph
Ph
5
N
Boc
10b
, 91% yield,
90% ee
10d
, 55% yield,
84% ee
10c
, 47% yield,
86% ee
10a
, 80% yield,
96% ee
a Conditions: 7 (0.20 mmol), 8 (0.10 mmol), 1a (2 mol%), 9b (20 mol%)
and 2,6-lutidine (0.36 mmol) were dissolved in DMF (0.6 M) under N2
atmosphere and blue LED irradiation. Yields determined after flash
chromatography. ee determined by SFC-LC using chiral columns.
Mechanistic Insights. For transition metal photocatalysts based on Ru(II) or Ir(III), the
mechanisms described in the literature for these three transformations proceed via reductive
quenching of the photocatalyst.15,20-22 Based on those precedents, we initially postulated that the
platinum complexes 1 could also follow a reductive pathway. Scheme 1 outlines the mechanism
involved in the three transformations, focusing on the redox processes of the photocatalyst. It is
also important to mention that the photocatalytic -alkylation of aldehydes is a complex
mechanism, that involves a propagation process and the photocatalyst is reported to act mainly in
the initiation step.23 Taking into account these considerations, the mechanistic pathway would be
as follows: the visible-light irradiation of the Pt(II) complex will generate an excited state of the
catalyst, which will react with an amine present in the media to give the one-electron reduced
photocatalyst (PC·-) and the corresponding amine radical cation. In the three transformations, there
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is an amine involved: the tetrahydroisoquinoline in the CDC reaction, triethylamine in the boronic
acid photooxidation and the enamine formed between the aldehyde and the organocatalyst in the
-alkylation of aldehydes. Next, the reduced photocatalyst will be oxidized by an oxygen molecule
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(left, Scheme 1), or by the alkyl bromoderivative (right, Scheme 1) to regenerate the initial Pt(II)
catalyst. The mechanistic proposal is in agreement with reported mechanisms which demonstrate
that the reactive oxygen species involved in these transformations is the oxygen radical anion.15,20
Reductive Pathway
R3N
R3N
R3N
R3N
PC*
PC*
PC
PC
Br
R'
O2
h
h
R'
PC
PC
N
O2
O
Br
R3N:
R3N:
, Et3N
Ph
NMe
N
tBu
Ph
R
Scheme 1. Reductive quenching mechanism based on previous examples reported in the literature.
In order to corroborate the proposed reductive pathway, luminescent quenching experiments
were performed. Firstly, we carried out emission quenching studies of catalyst 1b by triethylamine
24
or O2 . The platinum complex 1b was selected because it is the most soluble complex, and thus
facilitates the experiment. Unfortunately, upon addition of triethylamine or oxygen, the emission
spectra of 1b did not change significantly, and in both cases, the quenching efficiency was very
similar. Therefore, since the oxygen quantification is difficult to be determined, we explore more
suitable quenching experiments, using bromomalonate and Et3N, which are typical reactants for
the debromination reactions. According to literature, the debromination of diethyl bromomalonate
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(8a) using Ru(bpy)32+ 25 or organic dyes such as riboflavin26 in the presence of amines as electron
and/or hydrogen donor involves a reductive quenching, in which the emission of the photocatalyst
is quenched by the addition of the amine but not by bromomalonate 8a. Following those precedents,
we carried out the quenching of the emission of complex 1b by bromomalonate 8a and
triethylamine27 (Figure 2). Based on the redox potential data, the oxidation potential of
triethylamine (Eoxp = 0.88 V vs Ag/AgCl) is easily reached by 1b (E*red = 1.47 V vs Ag/AgCl),
which should promote the reductive quenching of the excited state of the platinum(II) complex.
However, as illustrated in Figure 2A, an ineffective quenching of the emission of 1b was observed
upon addition of triethylamine, even at high concentration (0.8 M). Conversely, diethyl
bromomalonate (8a) (Eredp = -1.10 V vs Ag/AgCl) provokes an oxidative quenching of the excited
state of 1b (E*ox = -1.24 V vs Ag/AgCl). Combining all the quenching results, it can be concluded
that our family of platinum(II) complexes is more prone to oxidative than reductive processes.
This behavior could be due to the electron-donating ability of the 8-hydroxy or -thio quinolines
ligands may be difficult to accept an electron by the excited state of the resulting metallic
complex.28
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Considering all our results, the modified mechanistic proposal is outlined in Scheme 2 (see
S.I. for the complete catalytic cycle of each transformation). After irradiation under visible light,
the excited Pt(II) catalyst is firstly oxidized by the oxygen molecule (in the case of the oxidation
of boronic acids or CDC of THIQs) or the dialkyl bromomalonate (for the -alkylation of
aldehydes). Finally, the oxidized catalyst is reduced by a tertiary amine (triethylamine, THIQ
substrate or enamine intermediate, depending on the transformation) to regenerate the platinum(II)
photocatalyst.
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Figure 2. Quenching experiments of the emission of catalyst 1b by triethylamine (A) or diethyl
bromomalonate (8a) (B).
or
O2
R'
Br
O2
or
R'
Br
Oxidative
Pathway
PC*
PC
R3N
h
PC
R3N
Scheme 2. Oxidative pathway proposed for the photocatalytic activity of 8-substituted quinoline
Pt(II) complexes 1 in the oxidation of boronic acids, the CDC of THIQs and the -alkylation of
aldehydes.
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9
Photophysical characterization of the catalysts with ab initio calculations. In order to provide
insights into the different behavior of the catalysts employed 1a and 1b, we have performed high-
level ab initio simulations. First, we have characterized the bright state (S1), which is populated
after excitation with the light source (see S.I.). After vertical excitation to the bright state (S1), we
have considered the geometrical relaxation in this state. Therefore, we have optimized the
geometry of the S1 state at the TD-CAM-B3LYP/ANO-RCC-DZP level of theory, using the
Gaussian 09 (revision E.01)29 package. Ultrafine grid integration was used to obtained more
accurate results. In order to benchmark the geometries that are obtained with this method, we have
optimized the geometry of the S1 state of catalysts 1 at the multireference CASSCF(14,12)/ANO-
RCC-DZP level of theory, using MOLCAS 8.30 The largest geometrical difference was found in
the distance between the Pt and the S atom of the DMSO (0.08 Å), just 4% shorter.
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Figure 3. Relative energies (in eV) of the electronic states of 1a and 1b using the geometry of
the S1 state. Spin Orbit Coupling (SOC) between the S1 and the T1 states is also given (in cm-1).
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We have then characterized the vertical spectrum and the Spin Orbit Coupling (SOC) in the
S1 geometry. For this purpose, we have performed multistate multireference perturbation theory
calculations at the CASPT2(14,12)/ANO-RCC-DZP level of theory, also using MOLCAS 8.30 A
real shift of 0.1 a.u. was included in the CASPT2 calculations in order to avoid problems with
intruder states. Overlaps between the corresponding singlet and triplet states have been obtained
through Restricted Active Space – State Interaction (RASSI) calculations. Figure 3 shows the
relative energies of the first computed states using the S1 geometry. Catalyst 1a presents the lowest
difference between S1 and the first triplet T1. In addition, the spin orbit coupling between these
states of 1a is the largest one compared to the others. Therefore, it is more likely to populate the
T1 state. Among the two catalysts, in 1a the T1 state is the one at higher energy with respect to the
ground state S0. This implies that (i) a larger number of charge transfer states might be accessible
from T1 and (ii) a longer lifetime of this state. These differences explain the higher effectiveness
of catalysts 1a, as it has been experimentally shown. It also points out a possible mechanism, in
which the triplet T1 state might be involved in the charge transfer process, photocatalyzed
reduction.
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Therefore, the active band in the visible area corresponds with the first transition S0S1, and
the coupling with the T1 state is pointed out as a key step in the photoredox mechanism. The
catalyst molecular orbitals with higher contribution in the transitions S0S1 and S0T1 are shown
in Figure 4. These orbitals correspond to a combination of p orbitals of the aromatic system, d
orbitals of the Pt, and p orbitals of the coordinating O or S atoms. These results agree with the non-
innocent character of the 8-hydroxy or 8-mercapto-quinoline ligand, as previously mentioned. In
general, similar shapes are obtained for these two species. However, the electronic density
difference between the ground and excited state, (S0S1), of the catalyst 1a shows a much
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larger participation of the p orbital of the S atom. Therefore, the different nature and participation
of the p orbital of the S atom with respect to that of the O atom in the photoexcitation processes of
the complexes seems to be a key factor for understanding the higher activity of 1a in comparison
with the other catalyst (1b).
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Figure 4. Active molecular orbitals (isovalue = 0.02 a.u.) with larger contribution in the S0S1
and S0T1 transitions for catalysts 1a and 1b.
CONCLUSIONS
We have found that the mercaptoquinoline-Pt(II) complex 1a is a general and efficient
photocatalyst for the cross-dehydrogenative coupling, oxidation of aryl boronic acids and
asymmetric alkylation of aldehydes. Theoretical studies showed that the mercaptoquinoline
complex presents larger ability to couple the bright S1 state with the T1 one, which would explain
its higher activity in comparison with the oxygen platinum complex. Moreover, although the
complexes are able to accomplish both oxidative and reductive pathways, the luminescent
quenching experiments show that this family of Pt(II) complexes follow an oxidative quenching
mechanism.
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EXPERIMENTAL SECTION
General Information.
7
8
9
1H NMR were recorded on a Bruker AV-300 or a Varian AV-400 at 300 and 400 MHz, respectively.
The chemical shifts ( reported in ppm) for 1H NMR are referenced to tetramethylsilane (0 ppm)
or to the residual non-deuterated solvent peak (CDCl3 at 7.26 ppm and DMSO-d6 at 2.50 ppm).
Coupling constants are given in Hz. The following abbreviations were used to indicate the
multiplicity: s, singlet; d, doublet; dd, double doublet; ddd, double double doublet; dt, doublet
triplet; t, triplet; td, triplet doublet; q, quartet; m, multiplet; bs, broad singlet; bd, broad doublet.
UV-Vis measurements were acquired on an Agilent 8453 UV-Vis Spectrophotometer controlled
by UV-Visible ChemStation Software. HPLC grade CH3CN solvent and a Teflon-top 10x10 mm
precision cell made of quartz SUPRASIL® were used for all measurements.
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Emission spectra were recorded on a JASCO Spectrofluorometer FP-8600 equipped with a TC-
815 Peltier thermostated single cell holder (water-cooled) controlled by Spectra Manager Version
2.10.01. HPLC grade CH3CN solvent and a 10x10 mm light path quartz SUPRASIL® cuvette
equipped with a silicone/PTFE septum were used for all measurements.
Emission spectra of the light sources used for the photochemical reactions were recorded on an
optical spectrometer StellarNet model Blue-Wave UV-NB50.
Cyclic Voltammetry (CV) experiments were acquired on an IVIUM Technologies CompactStat
controlled by IviumSoft version 2.124 offering a compliance voltage of up to ± 100 V (available
at the counter electrode), ± 10 V scan range and ± 1 A current range. HPLC grade CH3CN solvent
was used for all measurements. Tetra-n-butylammonium hexafluorophosphate was used as
supporting electrolyte at 0.1 M concentration. All cyclic voltammetry experiments were performed
using a conventional three-electrode system, containing a coiled Pt wire acting as counter electrode,
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an Ag/AgCl saturated solution as reference electrode and a glassy carbon working electrode (A =
0.071 cm2) at 20 mV/s scan rate. All the electrodes were purchased from Metrohm. Redox-active
species were dissolved at 1.0 mM concentration, and these solutions were thoroughly purged with
Ar and kept under an inert atmosphere throughout the measurements.
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Enantiomeric excesses were determined in a Supercritical Fluid Chromatography (SFC). The
chromatograms were acquired on an Agilent Technologies 1260 Infinity Series instrument with a
SFC module and a UV-Vis detector, employing Daicel Chiralpak IA and IC chiral columns. The
exact conditions for the analysis are specified in each case.
Materials and Methods.
All reagents and materials were purchased from commercial sources and used without further
purification while anhydrous solvents were taken from a SPS solvent dispenser or distilled over
CaH2 or sodium with benzophenone as indicator. Chromatographic purification was accomplished
using Flash Chromatography (FC) on Merck Geduran® Si 60 Silica Gel (40-63 m). Thin Layer
Chromatography (TLC) was performed on Merck precoated TLC plates (silica gel 60 F254) and a
solution of KMnO4, I2 or phosphomolybdic acid was served as staining agent. 1,2,3,4-
Tetrahydroisoquinolines 2a-b31 and 2c-d,32 and imidazolidinone catalysts 9a-b22d, 33 were prepared
according to the literature.
Different photocatalytic systems were used for performing the photochemical reactions (see Figure
S1): a) A household 23W CFL (Compact Fluorescence Lamp) with a fan for keeping the reaction
mixture at room temperature. b) A custom-made “light box” with 5 strips of blue LEDs (15 W)
attached around a test tube rack, with a fan for keeping the reaction mixture at room temperature.
c) A custom-made temperature-controlled system, in which the reaction mixture was kept at room
temperature by passing coolant through the metallic system employing a recirculating chiller, and
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the irradiation was achieved with a single LED (385 mW blue LED at 450 nm, 385 mW green
LED at 520 nm and 5000 K white LED) located 1 cm beneath the base of the vial. d) A blue LED
at 455 nm which irradiates the reaction media through a glass bar.
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Synthesis of platinum(II) complexes
Synthesis of cis-PtCl2(dmso)2:34 In a glass vial, K2PtCl4 (500 mg, 1.20 mmol), DMSO (279 L,
3.60 mmol) and distilled water (5 mL) were added. The reaction mixture was stirred at room
temperature in the absence of light. After 24 hours, the white solid obtained was filtered, washed
with distilled water (2 x 10 mL), ethanol (2 x 10 mL) and diethyl ether (2 x 10 mL) and dried under
1
vacuum, affording the Pt(II) complex (430 mg, 1.02 mmol, 85% yield). H NMR (300 MHz,
CDCl3)  3.59 (s, 6H).
General procedure for the synthesis of platinum(II) complexes 1a-b9
To a solution of NaOH (0.56 mmol) in MeOH (0.3 mL), the corresponding ligand (0.50 mmol)
was added and the resulting suspension was stirred until the ligand was completely dissolved.
Then, a suspension of cis-PtCl2(dmso)2 (0.45 mmol) in acetone (0.6 mL) was added and the
reaction mixture was stirred at room temperature. After 24 hours, the solid obtained was filtered,
washed with cold water (2 x 10 mL) and diethyl ether (2 x 10 mL) and dried under vacuum.
Synthesis of complex 1a:9 1a was obtained following the general procedure as a dark red solid
(200 mg, 0.44 mmol, 98%). 1H NMR (300 MHz, DMSO-d6)  9.36 (d, J = 4.0 Hz, 1H), 8.66 (d,
J = 8.7 Hz, 1H), 7.76 – 7.72 (m, 1H), 7.63 (t, J = 7.8, 1H), 7.55 – 7.48 (m, 2H), 3.61 (s, 6H).
Synthesis of complex 1b:9 1b was obtained following the general procedure as a yellowish-orange
solid (165 mg, 0.35 mmol, 78%). 1H NMR (300 MHz, DMSO-d6)  9.38 (d, J = 4.6 Hz, 1H), 8.66
(d, J = 8.7 Hz, 1H), 7.70 (dd, J = 8.3, 4.9 Hz, 1H), 7.49 (t, J = 7.8 Hz, 1H), 7.17 (d, J = 7.9 Hz,
1H), 7.01 (d, J = 8.0 Hz, 1H), 3.61 (s, 6H).
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General procedures for photochemical cross-dehydrogenative coupling
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General procedure A: To an oven-dried glass vial equipped with a magnetic stir bar, THIQ
derivative 2 (0.2 mmol), the corresponding nucleophile 3 (0.3 – 0.6 mmol, specified in each case),
photocatalyst 1a (0.002 mmol) and CH3CN dry (2 mL) were added. The mixture was purged with
oxygen for 5 minutes. Then, the vial was irradiated (a blue LED custom-made “light box” was
used, Figure S1b) and stirred at room temperature until the reaction was completed (checked by
1H NMR or TLC). The crude reaction mixture was filtered through a plug of silica and the solvent
was removed under reduced pressure. The yield was determined by flash chromatography on silica
gel or by 1H NMR using CH2Br2 as internal standard (specified in each case).
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General procedure B: To an oven-dried schlenk flask equipped with a magnetic stir bar, THIQ
derivative 2 (0.2 mmol), the corresponding nucleophile 3 (0.6 mmol), photocatalyst 1a (0.01
mmol) and a 1:1 mixture of toluene/water (1 mL) were added. The mixture was irradiated through
a glass bar by a blue LED at 455 nm (Figure S1d) and stirred at room temperature open air. After
18 h, excess of nucleophile was distilled under vacuum at 50 °C to obtain the desired product.
Dimethyl 2-(2’-phenyl-1’,2’,3’,4’-tetrahydroisoquinolin-1-yl) malonate (4aa):16a The general
procedure A was followed using THIQ 2a (41.9 mg, 0.2 mmol, 1.0 equiv.) and dimethyl malonate
3a (28 L, 0.24 mmol, 1.2 equiv.). The crude reaction mixture was purified by flash
chromatography (20:1 cyclohexane:EtOAc) to afford 4aa (32.6 mg, 0.096 mmol, 48%). 1H NMR
(300 MHz, CDCl3)  7.28-7.07 (m, 6H), 6.99 (d, J = 8.6 Hz, 2H), 6.77 (t, J = 6.8 Hz, 1H), 5.72
(d, J = 9.4 Hz, 1H), 3.96 (d, J = 9.4 Hz, 1H), 3.81 – 3.59 (m, 5H), 3.56 (s, 3H), 3.15-3.00 (m, 1H),
2.88 (dt, J = 16.5, 5.0 Hz, 1H).
2-Phenyl-1,2,3,4-tetrahydroisoquinoline-1-carbonitrile (4ab):16a The general procedure A was
followed using THIQ 2a (41.9 mg, 0.2 mmol, 1.0 equiv.) and malonitrile 3b (22 L, 0.40 mmol,
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2.0 equiv.). The crude reaction mixture was purified by flash chromatography (24:1
5
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1
cyclohexane:EtOAc) to afford 4ab (24.4 mg, 0.104 mmol, 52%). H NMR (300 MHz, CDCl3)
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8
9
 7.43-7.21 (m, 5H), 7.10 (d, J = 7.8 Hz, 2H), 7.03 (t, J = 7.3 Hz, 1H), 5.52 (s, 1H), 3.82-3.75 (m,
1H), 3.50 (ddd, J = 12.4, 10.7, 4.1 Hz, 1H), 3.18 (ddd, J = 16.4, 10.6, 5.9 Hz, 1H), 2.98 (dt, J =
16.1, 3.5 Hz, 1H).
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1-(Nitromethyl)-2-phenyl-1,2,3,4-tetrahydroisoquinoline (4ac):16a The general procedure A
was followed using THIQ 2a (41.9 mg, 0.2 mmol, 1.0 equiv.) and nitromethane 3c (13 L, 0.24
mmol, 1.2 equiv.). The crude reaction mixture was purified by flash chromatography (10:1
1
cyclohexane:EtOAc) to afford 4ac (28.4 mg, 0.106 mmol, 53%). H NMR (300 MHz, CDCl3)
 7.34-7.10 (m, 6H), 6.98 (d, J = 8.0 Hz, 2H), 6.85 (t, J = 7.3 Hz, 1H), 5.55 (t, J = 7.2 Hz, 1H),
4.88 (dd, J = 11.8, 7.8 Hz, 1H), 4.57 (dd, J = 11.8, 6.7 Hz, 1H), 3.75-3.55 (m, 2H), 3.18-3.02 (m,
1H), 2.80 (dt, J = 16.5, 4.9 Hz, 1H).
Diethyl (2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phosphonate (4ad):16a The general
procedure B was followed using THIQ 2a (41.9 mg, 0.2 mmol, 1.0 equiv.) and triethylphosphite
3d (103 L, 0.60 mmol, 3.0 equiv.). The product 4ad (56.6 mg, 0.164 mmol, 82%) was obtained
pure after distilling off of the excess of nucleophile. 1H NMR (300 MHz, CDCl3)  7.43-7.34 (m,
1H), 7.29-7.13 (m, 5H), 6.99 (d, J = 8.3 Hz, 2H), 6.80 (t, J = 7.3 Hz, 1H), 5.20 (d, J = 20.0 Hz,
1H), 4.17-3.82 (m, 5H), 3.65-3.61 (m, 1H), 3.07-3.02 (m, 2H), 1.26 (t, J = 7.1 Hz, 3H), 1.15 (t, J
= 7.1 Hz, 3H).
Dimethyl 2-(2-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)malonate (4ba):16a The
general procedure A was followed using THIQ 2b (47.9 mg, 0.2 mmol, 1.0 equiv.) and dimethyl
malonate 3a (28 L, 0.24 mmol, 1.2 equiv.). The product 4ba (34.0 mg, 0.092 mmol, 46%) was
obtained pure after distilling off of the excess of nucleophile. 1H NMR (300 MHz, CDCl3)  7.24–
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7.15 (m, 2H), 7.13–7.00 (m, 2H), 6.92 (bd, J = 9.1 Hz, 2H), 6.78 (bd, J = 9.1 Hz, 2H), 5.49 (d, J
= 9.4 Hz, 1H), 3.96 (d, J = 9.4 Hz, 1H), 3.73 (s, 3H), 3.69–3.64 (m, 1H), 3.63 (s, 3H), 3.61 (s, 3H),
3.59–3.50 (m, 1H), 3.01 (ddd, J = 16.6, 10.2, 6.3 Hz, 1H), 2.75 (dt, J = 16.7, 4.4 Hz, 1H).
Diethyl 2-(2-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)malonate (4be):16a The
general procedure A was followed using THIQ 2b (47.9 mg, 0.2 mmol, 1.0 equiv.) and diethyl
malonate 3e (37 L, 0.24 mmol, 1.2 equiv.). The product 4be (48.5 mg, 0.122 mmol, 61%) was
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obtained pure after distilling off the excess of nucleophile. 1H NMR (300 MHz, CDCl3)  7.28–
7.22 (m, 1H), 7.19–7.04 (m, 3H), 6.91 (d, J = 9.1 Hz, 2H), 6.77 (d, J = 9.1 Hz, 2H), 5.51 (d, J =
9.2 Hz, 1H), 4.20–4.01 (m, 4H), 3.90 (d, J = 9.2 Hz, 1H), 3.72 (s, 3H), 3.70–3.61 (m, 1H), 3.60–
3.50 (m, 1H), 3.01 (ddd, J = 16.5, 10.2, 6.3 Hz, 1H), 2.76 (dt, J = 16.7, 4.4 Hz, 1H), 1.14 (q, J =
7.1 Hz, 6H).
1-Allyl-2-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline (4bf):35 The general procedure A
was followed using THIQ 2b (47.9 mg, 0.2 mmol, 1.0 equiv.) and potassium allyltrifluoroborate
3f (35.5 mg, 0.24 mmol, 1.2 equiv.). The crude reaction mixture was purified by flash
chromatography (20:1 pentane:EtOAc) to afford 4af (26.3 mg, 0.094 mmol, 47%). 1H NMR (300
MHz, CDCl3)  7.20-7.08 (m, 4H), 6.95-6.76 (m, 4H), 5.94-5.76 (m, 1H), 5.09-5.03 (m, 1H), 5.00
(bs, 1H), 4.62 (t, J = 6.7 Hz, 1H), 3.76 (s, 3H), 3.65-3.46 (m, 2H), 3.05-2.90 (m, 1H), 2.85-2.62
(m, 2H), 2.55-2.40 (m, 1H).
5-(4-Chlorobenzyl)-4b,5,12,13-tetrahydro-6H-isoquinolino[2,1-a]quinazolin-6-one
(4c):32
The general procedure A was followed using THIQ 2c (68.5 mg, 0.2 mmol, 1.0 equiv.) in an
intramolecular reaction. The crude reaction mixture was purified by flash chromatography (9:1
petroleum ether:EtOAc) to afford 4c (39.5 mg, 0.116 mmol, 58%). 1H NMR (300 MHz, CDCl3)
 7.96 (dd, J = 7.7, 1.5 Hz, 1H), 7.36 (ddd, J = 8.7, 7.3, 1.6 Hz, 1H), 7.28–7.14 (m, 7H), 7.06–
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7.01 (m, 1H), 6.93–6.83 (m, 2H), 5.65 (s, 1H), 5.55 (bs, 1H), 4.37 (d, J = 15.5 Hz, 1H), 4.04–3.90
(m, 1H), 3.50 (ddd, J = 14.1, 10.9, 5.7 Hz, 1H), 3.16–2.96 (m, 1H), 2.73 (ddd, J = 16.9, 5.4, 2.4
Hz, 1H).
5-Benzyl-4b,5,12,13-tetrahydro-6H-isoquinolino[2,1-a]quinazolin-6-one (4d):32 The general
procedure A was followed using THIQ 2d (75.4 mg, 0.2 mmol, 1.0 equiv.) in an intramolecular
reaction. The crude reaction mixture was purified by flash chromatography (9:1 petroleum
ether:EtOAc) to afford 4d (58.5 mg, 0.156 mmol, 78%). 1H NMR (300 MHz, CDCl3)  7.89 (dd,
J = 7.7, 1.7 Hz, 1H), 7.34–7.15 (m, 7H), 7.13–7.07 (m, 2H), 7.00–6.87 (m, 1H), 6.85–6.75 (m,
2H), 5.64 (bd, J = 14.5 Hz, 1H), 5.60 (s, 1H), 4.29 (d, J = 15.3 Hz, 1H), 3.99 – 3.84 (m, 1H), 3.44
(ddd, J = 14.2, 11.1, 5.8 Hz, 1H), 3.13 – 2.93 (m, 1H), 2.64 (ddd, J = 17.0, 5.8, 2.4 Hz, 1H).
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General procedure for photochemical oxidation of aryl boronic acids
To a glass vial equipped with a magnetic stir bar, the corresponding aryl boronic acid 5 (0.10
mmol), photocatalyst 1a (0.002 mmol), triethylamine (0.11 mmol) and anhydrous DMF (2 mL)
were added. The vial was irradiated (a 5000 K white single LED in a custom-made temperature-
controlled system was used, Figure S1c) and stirred open-to-air at room temperature until the
reaction was completed (checked by 1H NMR or TLC). The crude reaction mixture was diluted in
water (10 mL) and extracted with diethyl ether (2 x 10 mL). The combined organic layers were
washed with brine (10 mL), dried over MgSO4 and concentrated under reduced pressure. The
yields of the corresponding products were determined either by flash chromatography on silica gel
1
or by H NMR using nitromethane as internal standard, depending on the boiling point of the
obtained product (specified in each case).
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Phenol (6a):20b The general procedure was followed using phenylboronic acid, leading to the
5
6
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product 6a (8.6 mg, 0.09 mmol) in 91% yield determined by NMR internal standard. H NMR
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(300 MHz, CDCl3)  7.28 – 7.21 (m, 2H), 6.97 – 6.90 (m, 1H), 6.86 – 6.81 (m, 2H), 4.69 (s, 1H).
4-Methylphenol (6b):20b The general procedure was followed using phenylboronic acid, leading
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to the product 6b (6.5 mg, 0.06 mmol) in 60% yield determined by NMR internal standard. H
NMR (300 MHz, CDCl3)  7.04 (d, J = 8.0 Hz, 2H), 6.73 (d, J = 8.5 Hz, 2H), 4.56 (s, 1H), 2.28
(s, 3H).
3,5-Dimethylphenol (6c):36 The general procedure was followed using phenylboronic acid,
leading to the product 6c (8.6 mg, 0.07 mmol) in 70% yield determined by NMR internal standard.
1H NMR (300 MHz, CDCl3)  6.58 (s, 1H), 6.46 (s, 2H), 2.26 (s, 6H).
4-Methoxyphenol (6d):20b The general procedure was followed using 4-methoxyphenylboronic
acid, leading after flash chromatography on silica gel (100% DCM) to the product 6d (11.0 mg,
0.09 mmol, 89%). 1H NMR (300 MHz, CDCl3)  6.91 - 6.66 (m, 4H), 4.61 (bs, 1H), 3.77 (s, 3H).
4-Hydroxybenzonitrile (6e):20b The general procedure was followed using 4-cyanophenylboronic
acid, leading after flash chromatography on silica gel (100% DCM) to the product 6e (9.6 mg, 0.08
mmol, 81%). 1H NMR (300 MHz, CDCl3)  7.56 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H),
6.03 (bs, 1H).
3,5-Bis(trifluoromethyl)phenol (6f):37 The general procedure was followed using phenylboronic
acid, leading to the product 6f (20.2 mg, 0.09 mmol) in 88% yield determined by NMR internal
standard. 1H NMR (300 MHz, CDCl3)  7.45 (s, 1H). 7.28 (s, 2H), 5.62 (s, 1H).
4-Chlorophenol (6g):20b The general procedure was followed using phenylboronic acid, leading
1
to the product 6g (9.0 mg, 0.07 mmol) in 70% yield determined by NMR internal standard. H
NMR (300 MHz, CDCl3)  7.19 (d, J = 8.9 Hz, 2H), 6.77 (d, J = 8.9 Hz, 2H), 4.71 (s, 1H).
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5-Hydroxyindole (6h):38 The general procedure was followed using 5-indolylboronic acid,
leading after flash chromatography on silica gel (3:2 cyclohexane:EtOAc) to the product 6h (6.4
mg, 0.05 mmol, 48%). 1H NMR (300 MHz, CDCl3)  8.05 (bs, 1H), 7.26 (d, J = 8.2 Hz, 1H), 7.19
(t, J = 2.8 Hz, 1H), 7.05 (d, J = 2.3 Hz, 1H), 6.78 (dd, J = 8.6, 2.4 Hz, 1H), 6.44 (s, 1H), 4.50 (bs,
1H).
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General procedure for photochemical -alkylation of aldehydes
To an oven-dried glass vial, the corresponding aldehyde 7 (0.20 mmol), organic bromide 8 (0.10
mmol), organocatalyst 9b (0.02 mmol) and photocatalyst 1a (0.002 mmol) were added. Then,
anhydrous DMF (200 L) and 2,6-lutidine (0.20 mmol) were added to the vial. The vial was closed
with a PTFE/rubber septum and the reaction mixture was degassed by three freeze-pump-thaw
cycles. Afterwards, the reaction mixture was stirred and irradiated (a 385 mW single blue LED in
a custom-made temperature-controlled system was used, Figure S1c) at room temperature. Upon
consumption of the corresponding organic bromide, the solvent was removed under reduced
pressure and the crude reaction mixture was purified by flash chromatography on silica gel to
afford the corresponding alkylated aldehyde 10. For the determination of the enantiomeric
excess, the crude reaction mixture was directly derivatized through a Wittig reaction. After
removing
the
solvent
from
the
reaction
mixture,
2
equivalents
of
benzyl(triphenylphosphoranylidene)acetate and 1 mL of DCM were added. Then, the vial was
closed and the mixture was stirred at reflux until the reaction was completed. Finally, the crude
reaction mixture was purified by flash chromatography to afford the corresponding derivatized
product which was analysed by SFC on chiral columns.
The absolute configuration of the alkylated aldehydes was determined in comparison to those
reported previously by our group, since the same equipment and conditions were used.22d
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