Visible-light photoredox synthesis of internal alkynes containing quaternary carbons

Article abstract of DOI:10.1039/c6cc01632d

A novel and efficient visible-light photoredox method for the synthesis of internal alkynes containing quaternary carbons has been developed via coupling reactions of N-phthalimidoyl oxalates of tert-alcohols with 1-(2-(arylsulfonyl)ethynyl)benzenes. The reactions proceeded well at room temperature with good functional group tolerability.

Full text of DOI:10.1039/c6cc01632d

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Communication
Visible-light photoredox synthesis of internal alkynes containing
quaternary carbons
Chang Gao,a,b Jingjing Li,a Jipan Yu,a Haijun Yanga and Hua Fu*a,b
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
A novel and efficient visible-light photoredox method for
synthesis of internal alkynes containing quaternary carbons
Table 1 Optimization of conditions on visible-light photoredox coupling of N-
50 phthalimidoyl oxalate 1a with 1-(2-(phenylsulfonyl)ethynyl)benzene (2a)a
has been developed via couplings of N-phthalimidoyl oxalates
of tert-alcohols with 1-(2-(arylsulfonyl)ethynyl)benzenes. The
10 reactions were performed well at room temperature with
good functional group tolerability.
Ru(bpy)3Cl2
HE, additive
solvent, rt, Ar
Me
O
Me
O
S
O
O
O
Ph
+
40 W CFL
O
O
N
3a
2a
1a
2
O
2Cl
N
Ru
N
Internal alkyne intermediates are important building blocks, and
they are widely used in synthesis of antibiotics,1 antimycotics,2
polymers, optical or electronic materials, and liquid crystals.3 The
15 traditional method for synthesis of internal alkynes is through
palladium/copper co-catalyzed Sonogashira couplings of terminal
alkynes with aryl halides,4 and the corresponding C(sp2)–C(sp)
bonds are constructed.5 The protocol shows high efficiency with
tolerance of functional groups. However, diversity of the
20 synthesized products is limited by using this strategy. Recently,
other transition-metal catalysts6 such as ruthenium,7 indium,8
gold,9 silver,10 cobalt,11 nickel,12 copper,13 and iron14 have been
N
N
N
N
Ru(bpy)3Cl2
Yield
(%)b
16
1a
2a
Entry
Additive
Solvent
(equiv)
1
(equiv)
1.5
1
2
iPr2NEt
DCM
DCM
1
1.5
1.5
1.5
1.5
1.5
1
iPr2NEt.HBF4
iPr2NEt.HBF4
iPr2NEt.HBF4
iPr2NEt.HBF4
iPr2NEt.HBF4
42
15
3
1
MeCN
DMF
o
4
1
53
developed. Unfortunately, the higher temperatures (80 ~ 135 C)
and appropriate ligands are usually necessary, which leads to
25 higher cost and is not favor for construction of some functional
molecules. It is a long-term goal to develop less expensive, more
highly efficient catalyst systems to make diverse internal alkynes
under mild conditions. Recently, visible-light photoredox
catalysis has emerged as a powerful activation protocol in new
30 chemical transformations,15 and great achievements have been
made on photoredox decarboxylative couplings of carboxylic
acids and their derivatives.16 Alcohols widely occur in organic
molecules, natural products and biomasses, and their chemical
transformations provide diverse compounds. Interestingly,
35 Overman and co-workers have developed visible-light
photoredox coupling of electron-deficient alkenes with tert-alkyl
N-phthalimidoyl oxalate intermediates that were easily prepared
from reaction of tertiary alcohols with chloro N-phthalimidoyl
oxalate.17 However, development of tert-alkyl N-phthalimidoyl
40 oxalate derivatives is limited. Chen and co-workers reported that
5
1
THF
55
78c
82c
38c
80c,d
79c,e
35c
NRc,f
NRc,g
6
1
THF/DCM
7
1.5
1.5
1.5
1.5
1.5
1.5
1.5
iPr2NEt.HBF4 THF/DCM
8
1
iPr2NEt
iPr2NEt.HBF4
iPr2NEt.HBF4
-
iPr2NEt.HBF4
iPr2NEt.HBF4
THF/DCM
THF/DCM
THF/DCM
THF/DCM
THF/DCM
THF/DCM
9
1
10
11
12
13
1
1
1
1
a Reaction conditions: under argon atmosphere and irradiation of visible
light, Ru(bpy)3Cl2 (1 μmol), 1a (0.1 mmol for entries 1-6; 0.15 mmol for
entries 7-12), 2a (0.15 mmol for entries 1-6; 0.1 mmol for entries 7-12),
Hantzsch ester (HE) (0.15 mmol), additive (0.12 mmol), solvent (2 mL),
time (8 h) in a sealed Schlenk tube. b Isolated yield. c Using a mixed
solvent of THF (1 mL) and DCM (1 mL). Using iPr2NEt.HBF4 (0.1
mmol) as the additive. e Using iPr2NEt.HBF4 (0.25 mmol) as the additive.
d
1-(2-(arylsulfonyl)ethynyl)benzenes
were
useful
radical
acceptors.18 To the best of our knowledge, it is difficult to make
internal alkynes containing quaternary carbons with terminal
alkynes and alkyl halides. Herein, we report visible-light
45 photoredox decarboxylative coupling of tert-alkyl N-
f
g
In the absence of photocatalyst. No light. DCM = dichloromethane.
CFL = compact fluorescent light.
Initially, coupling of N-phthalimidoyl oxalate 1a with 1-(2-
(phenylsulfonyl)ethynyl)benzene (2a) was used as the model
reaction to optimize conditions including ratio of 1a and 2a,
55 additives and solvents in 8 h under atmosphere of argon and
phthalimidoyl
oxalate
derivatives
with
1-(2-
(arylsulfonyl)ethynyl)benzenes leading to internal alkynes
containing quaternary carbons.
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Page 2 of 3
irradiation of visible-light with 40 W compact fluorescent light
displayed higher reactivity than those containing electron-
(CFL). As shown in Table 1, six solvents were tested using 1.0 25 donating groups, and the substrates with electron-donating
View Article Online
DOI: 10.1039/C6CC01632D
at ortho- and meta-sites. The coupling reactions could tolerate
various functional groups including ether (3c and 3d), thioether
(3e), carbon-halogen bonds (3f-k), ester groups (3l-n), naphthyl
mol% [Ru(bpy)3]Cl2 as the photoredox catalyst, one equiv of 1a
and 1.5 equiv of 2a as the substrates, 1.2 equiv of iPr2NEt.HBF4
as the additive in the presence of Hantzsch ester (HE) (entries 1-
6), and mixed solvent of THF and dichloromethane (DCM)
substituents at para-site of aryl rings gave lower yields than those
5
provided the highest yield (entry 6). When ratio of 1a and 2a was 30 (3o) and S-heterocycle (3p) on the aryl rings, and but the
changed into 1.5 equiv of 1a and one equiv of 2a as the substrates,
substrates with thioether (3e), C-F bond (3f) and S-heterocycle
(3p) provided lower yields. Furthermore, N-phthalimidoyl
oxalates of various tert-alcohols were surveyed. First, different-
sized cyclic N-phthalimidoyl oxalates were tested (3q-x), and
yield increased (entry 7). The reactivity greatly decreased using
10 iPr2NEt as the additive (entry 8). When amount of iPr2NEt.HBF4
was changed, yield slightly decreased (entries 9 and 10). Only
35% yield was afforded in the absence of additive (entry 11). The 35 they showed high reactivity. Unfortunately, product 3y
reaction did not work without photocatalyst (entry 12) or light
(entry 13).
containing adamantane was obtained in only 35% yield for
occurrence of unknown by-products. Subsequently, we
determined non-cyclic N-phthalimidoyl oxalates, and they
afforded reasonable yields (3z-ac). Interestingly, the substrates
40 containing amide (3ab) and silylether (3ac) were also acceptable
substrates. We attempted visible-light photoredox coupling of N-
phthalimidoyl oxalate (1a) (1.5 mmol) with 1-(2-
(phenylsulfonyl)ethynyl)benzene (2a) (1.0 mmol), and the target
product 3a was obtained in 58% (114 mg) yield.
15 Table 2 Substrate scope on the visible-light photoredox synthesis of
internal alkynes containing quaternary carbonsa
R1
Ru(bpy)3Cl2, HE
iPr2NEt.HBF4
THF/DCM, rt, Ar
R2
O
O
O
O
R1
O
R2
R3
O
S
R3
+
Ar
Ph
N
40 W CFL, 8 h
O
Ar
2
3
1
O
Yield (%)b
iPr2NEt.HBF4
+
HE.HBF4
iPr2NEt +
HE
Me
Me
Me
Me
.
OMe
EtO2C
CO2Et
EtO2C
CO2Et
Me
Me
or
iPr2NEt
or
iPr2NEt
Me
N
H
H
Me
+
N
I
3a (82%)
3b (53%)
3c (84%)
3d (89%)
A
Me
Me
OMe
Me
Cl
Me
Me
Me
3g (74%)
3h (86%)
3f (48%)
3e (39%)
+
[Ru(bpy)32+]*
Ru(bpy)3
F
SMe
R1
R2
R3
Cl
O
O
O
O
Me
Me
Me
Me
CO2Me
Br
O
N
1
visible light
3j (72%)
3k (58%)
3l (84%)
O
3i (71%)
2+
Ru(bpy)3
Br
Br
R1
R2
-
O
O
O
O
R1
R1
R2
R3
.
R3
Me
Me
Me
Me
R2
.
O
O
N
R3
.
S
B
CO2
E
O
3m (92%)
3n (85%)
3p (44%)
D
3o (73%)
O
-
CO2Et
O
O
Ph
CO2Et
S
CO2
+
N
O
Et
2
Me
Me
Me
Me
Me
O
C
Me
Ar
3u (84%)
R2 R1
R3
3s (71%)
3t (61%)
3q (77%)
Me
.
EtO2C
Me
CO2Et
Me
.
.
HE
PhSO2H
PhSO2
R1
N
H
H
Ar
G
R2
R3
Me
Me
PhO2S
Me
Me
F
3y (35%)
Ar
3
3w (82%)
3x (79%)
45
3v (73%)
Scheme 1 A plausible mechanism on the visible-light photoredox
synthesis of internal alkynes
Me Me
Si
Boc-N
O
Me
Me
Me
Me
We investigated mechanism on the visible-light photoredox
synthesis of internal alkynes. A plausible mechanism is suggested
3ac (65%)
3z (41%)
3ab (65%)
3aa (72%)
50 in Scheme 1. Reversible treatment of iPr2NEt.HBF4 and HE leads
a Reaction conditions: under argon atmosphere and irradiation of visible
light, Ru(bpy)3Cl2 (1 μmol), 1 (0.15 mmol), 2 (0.1 mmol), Hantzsch ester
(HE) (0.15 mmol), iPr2NEt.HBF4 (0.12 mmol), THF (1 mL), DCM (1
mL), time (8 h) in a sealed Schlenk tube. b Isolated yield.
to iPr2NEt (DIPEA) and HE.HBF4. Irradiation of Ru(bpy)32+ with
2+ *
visible light gives the oxidizing excited-state [Ru(bpy)3
]
II/I
2+ *
(E1/2*
= +0.77 V vs SCE in MeCN15a), and [Ru(bpy)3
]
red
accepts an electron from DIPEA (E1/2 = +0.65 V vs SCE in
55 MeCN) to provide Ru(bpy)3 leaving A. One electron in
After the optimized process above, substrate scope on the
visible-light photoredox synthesis of internal alkynes containing
20 quaternary carbons was investigated. As shown in Table 2,
reactivity of different 1-(2-(arylsulfonyl)ethynyl)benzenes (2)
was explored using 1a as the partner. The substrates containing
electron-withdrawing groups on the aromatic rings (see 3l-n)
+
+
Ru(bpy)3 transfers to oxygen of phthalimide in 1 provides
radical B regenerating catalyst Ru(bpy)32+, and leaving of
phthalimide anion (C) and the first carbon dioxide from B
donates carbonyl radical D, and subsequent desorption of the
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 3
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second carbon dioxide from D gives E.17 Addition of E to alkyne
3
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sulfone (2) forms radical F,18 and homolytic cleavage C-S bond
55
60
65
·
in F affords the desired internal akyne (3) freeing radical PhSO2
M. Alami, B. Crousse and F. Ferri, J. Organomet. Chem., 2001, 624,
DOI: 10.1039/C6CC01632D
(G). The similar radical C(sp3)-C(sp) couplings were reported in
the previous researches.19 Treatment of G with HE provides
PhSO2H freeing radical H, and reduction of [Ru(bpy)32+]* by H
gives Ru(bpy)3+ releasing I.
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5
4
5
Ru(bpy)3Cl2, HE
iPr2NEt.HBF4
THF/DCM, rt, Ar
Me
O
Me
O
O
O
6
7
X
+
40 W CFL, 8 h
O
N
3a
4a (X = Br)
4b (X = I)
1a
O
yield 40% (X = Br)
51% (X = I)
8
9
Scheme 2 Coupling of 1a with 1-(2-bromoethynyl)benzene (4a) or 1-(2-
10 iodoethynyl)benzene (4b) under the standard photoredox conditions
10 P. Li and L. Wang, Synlett, 2006, 2261.
70 11 L. Feng, F. Liu, P. Sun and J. Bao, Synlett, 2008, 1415.
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Coupling of 1a with 1-(2-bromoethynyl)benzene (4a) or 1-(2-
iodoethynyl)benzene (4b)20 leading to 3a was performed under
the standard photoredox conditions, and the reasonable yields
were afforded (Scheme 2). We investigated application of the
15 synthesized products. Reaction of 3a with trimethylsilyl azide
(TMSN3) in the presence of N-iodosuccinimide (NIS) gave 5
containing azido in 63% yield (Scheme 3), which is useful for
further structural modification.
75
80
85
Krchňák, P. Helquist and S. M. Canham, Org. Lett., 2004, 6, 2909;
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and M. Parisi, Org. Lett., 2003, 5, 3843; (i) P. Saejueng, C. G. Bates
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Me
NIS, rt, 36 h
MeCN/DCE
N3
N3
Ph
Me
+
TMSN3
0.44 mmol
O
Ph
3a
0.2 mmol
14 M. Carril, A. Correa and C. Bolm, Angew. Chem. Int. Ed., 2008, 47,
4862.
5 (63% yiled)
15 For selected reviews on visible-light photoredox catalysis, see: (a) C.
K. Prier, D. A. Rankic and D. W. C. MacMillan, Chem. Rev., 2013,
113, 5322; (b) J. M. R. Narayanam and C. R. J. Stephenson, Chem.
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20 Scheme 3 Reaction of 3a with TMSN3 in the presence NIS
In summary, we have developed a novel and efficient method
for visible-light photoredox synthesis of internal alkynes
containing quaternary carbons. The protocol used readily
available N-phthalimidoyl oxalates of tert-alcohols and 1-(2-
25 (arylsulfonyl)ethynyl)benzenes as the starting materials, and the
reactions were performed well at room temperature with good
tolerance of functional groups. Various novel internal alkynes
were prepared by using the present method, but it is difficult to
make them in the previous methods. Therefore, the development
30 of this method enriches synthesis of internal alkynes, and we
believe that it will be of wide applications.
90
95
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100
105
Financial support for this work was provided by the National
Natural Science Foundation of China (Grant Nos. 21372139 and
21221062),
and
Shenzhen
Sci
&
Tech
Bureau
35 (CXB201104210014A).
Notes and references
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