Photoredox Reaction of 2-Mercaptothiazolinium Salts with Silyl Enol Ethers

Article abstract of DOI:10.1021/acs.joc.9b02478

A method for the generation of free radicals from thiazolinium salts upon photocatalytic reduction is described. The thiazolinium salts are generated by treatment with methyl triflate of 2-mercaptothiazolines, which can be readily obtained from alkyl bromides and tosylates via a nucleophilic substitution reaction or by hydrothiolation of alkenes. Silyl enol ethers were used to trap the radicals, furnishing ketones after successive single-electron oxidation and elimination of the silyl cation.

Full text of DOI:10.1021/acs.joc.9b02478

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Note
Photoredox Reaction of 2-Mercaptothiazolinium Salts with Silyl Enol Ethers
Artem A. Zemtsov, Salavat S. Ashirbaev, Vitalij V. Levin, Vladimir
A. Kokorekin, Alexander A. Korlyukov, and Alexander D. Dilman
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02478 • Publication Date (Web): 06 Nov 2019
Downloaded from pubs.acs.org on November 6, 2019
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Photoredox Reaction of 2-Mercaptothiazolinium Salts with Silyl Enol Ethers
Artem A. Zemtsov,† Salavat S. Ashirbaev,† Vitalij, V. Levin,† Vladimir A. Kokorekin,†,‡ Alexander
A. Korlyukov,§,¶ Alexander D. Dilman,†,*
8
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†N. D. Zelinsky Institute of Organic Chemistry, 119991 Moscow, Leninsky prosp. 47, Russian
Federation, Fax: +7 499 135-53-28, E-mail: adil25@mail.ru
‡Sechenov First Moscow State Medical University, 119991 Moscow, Trubetskaya st. 8-2, Russian
Federation
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§A. N. Nesmeyanov Institute of Organoelement Compounds, 119991 Moscow, Vavilov str. 28,
Russian Federation
¶N. I. Pirogov Russian National Research Medical University, Ostrovitianov str., 1, 117997
Moscow, Russian Federation
MeOTf
N
S
R1
X
R1
S
OTMS
R2
Me
O
Ir(III)
blue LED
R1 = Me, 1° and 2° Alk, RfCH2
N
S
R1
S
R1
R2
R1
TfO
Abstract A method for the generation of free radicals from thiazolinium salts upon photocatalytic
reduction, is described. The thiazolinium salts are generated by treatment with methyl triflate of 2-
mercaptothiazolines, which can be readily obtained from alkyl bromides and tosylates via
nucleophilic substitution reaction, or by hydrothiolation of alkenes. Silyl enol ethers were used to
trap the radicals furnishing ketones after successive single electron oxidation and elimination of the
silyl cation.
Photoredox catalysis has emerged as a powerful methodology for carrying out reactions
involving free radicals.1 A radical species is generated with the aid of a catalyst, which after
activation by light serves as one-electron reductant or oxidant. The reductive pathway is typically
applied for the cleavage of carbon-heteroatom bond thereby providing carbon-centered radicals.
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However, this process efficiently works with certain types of substrates, prone to SET reduction
such as α-halocarbonyl compounds,2 perfluorinated compounds,3 and benzyl halides.4 At the same
time, the generation of unstabilized alkyl radicals from conventional alkyl halides with this method
is less frequent, apparently, because of their unfavorable redox potential.5,6 Herein we report that
alkylthio-substituted dihydrothiazolinium salts, which can be readily accessed from corresponding
alkyl halides and tosylates, or by an acid-promoted addition of 2-mercaptothiazoline to alkenes,
serve as excellent sources of alkyl radicals under standard photoredox conditions. Our idea is to
convert a poorly reducible neutral substrate into a cationic species capable of facile single electron
reduction with subsequent dissociation of the C-S bond (Scheme 1). As acceptors of alkyl radicals,
silyl enol ethers were selected, since they are known to be good components in photoredox
reactions.7,8
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A
A
S
Y
MeOTf
R
X
R
S
Y
Me
Y
Me
Y
Me
Y
A
+ e
A
A
R
+
R
S
R
S
S
TfO
Scheme 1. Generation of radicals.
A series of thio-substituted starting compounds were prepared from cyclopentyl bromide and
corresponding S-centered nucleophiles. Treatment of these compounds with methyl triflate for 15
min at 70 °C in dichloroethane generated triflate salts. Then, dichloroethane was evaporated under
vacuum, which also removed the excess of the volatile methylating agent. After addition of another
solvent, a photocatalyst (0.25 mol %) and silyl enol ether 5a, the mixture was irradiated with blue
light for 18 hours at room temperature (Table 1). N,N′-Dimethylpropyleneurea (DMPU, 1.2 equiv)
was also added as a basic scavenger of trimethylsilyltriflate formed as a by-product. Derivatives of
2-mercaptobenzothiazole (entries 1-3), dithiocarbamic acid (entry 4), and 2-mercaptoimidazole
(entry 5) in the presence of iridium and ruthenium catalysts showed moderate efficiency. The best
results were achieved using the derivative of 2-mercapto-thiazoline in combination with a cationic
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iridium complex. The use of a cheaper methylating agent, dimethylsulfate, gave inferior results
(entry 8). The coupling was successfully performed in dichloromethane and acetonitrile with yields
of 86% and 82%, respectively (entries 6 and 11). However, in all reactions using chlorinated
solvents, small amounts of trapping of the radicals (i.e. cyclopentyl) by chlorine were observed by
GC-MS analysis, and, for this reason, acetonitrile was used as solvent for further experiments.
Table 1. Optimization studies.
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(a) MeOTf (1.2 equiv)
70 °C, 15 min, DCE
OSiMe3
O
(b)
5a
(1.3 equiv)
Ph
Ph
6a
X
DMPU (1.2 equiv), cat. (0.25 mol %)
solv., blue LED, 18 h, rt
#
X
Solv.
Cat.
Y., %
40
1
N
ClCH2CH2Cl
[Ir(dtbbpy)(ppy)2]PF6
S
S
1
2
3
1
1
ClCH2CH2Cl
CH2Cl2
Ru(bpy)3(PF6)2
(25)a
60
[Ir(dtbbpy)(ppy)2]PF6
S
4
CH2Cl2
[Ir(dtbbpy)(ppy)2]PF6
53
S
N
N
2
N
N
5b,c
CH2Cl2
CH2Cl2
Ir(ppy)3
(18)b
86
S
S
Me
3
6
[Ir(dtbbpy)(ppy)2]PF6
S
4a
7c
4a
4a
4a
4a
4a
4a
4a
4a
4a
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
[Ir(dtbbpy)(ppy)2]PF6
[Ir(dtbbpy)(ppy)2]PF6
Ru(phen)3(BF4)2
84
60
8d
9
(29)a
78
10e
11
xantphos(neocup)CuBF4
[Ir(dtbbpy)(ppy)2]PF6
[Ir(dtbbpy)(ppy)2]PF6
[Ir(dtbbpy)(ppy)2]PF6
Ir(ppy)3
82
12f
13g
14b,c
15b,c,h
35
53
71
Ir(ppy)3
n.r.
aGC yield. b400 nm LED. cPPh3 (0.1 equiv) added. dMe2SO4 (1.2 equiv) instead of MeOTf. e0.5% of
cat. fNo DMPU. g4 hours. hBF3·OEt2 (1.2 equiv) instead of MeOTf.
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We evaluated a series of such transformations starting either from 2-mercaptothiazolines 4 or
from primary alkyl bromides 7 (Table 2). In the latter case, the corresponding derivatives 4 were
prepared from 7 by brief heating with a potassium salt of 2-mercaptothiazoline for 70 °C in
acetonitrile and used without further purification. The light-induced reaction of thiazolinium salts 8
proceeded smoothly with the sources of secondary radicals such as cyclopentyl (products 6b-e,j) or
isopropyl (products 6k,l). Non-stabilized primary radicals including methyl, di- and trifluorinated
ethyl radicals, as well as (trimethylsilyl)methyl radical, gave products 6 in reasonable yields. For
stabilized radicals, the satisfactory results were obtained starting from ethyl bromoacetate (product
6w), while the reaction with benzyl bromide was notably less efficient affording product 6x in only
38% yield. Concerning the silyl enol ether counterpart, derivatives of aromatic ketones worked
well. However, the enolates derived from aliphatic ketones proved to be not suitable for this
process. For example, the reactions of enol ether obtained from methyl tert-butyl ketone resulted in
complex mixtures, while the enol ether derived from -tetralone gave 1-silyloxynaphtalene as the
major product. For enolates bearing the naphthalene group or containing strong electron-
withdrawing trifluoromethyl or ester groups in the aromatic ring, reactions proceeded very slowly
under standard conditions. Fortunately, the replacement of the photocatalyst by more reducing
Ir(ppy)3 in combination with substoichiometric amounts of triphenylphosphine (0.2 equiv) allowed
successful preparation of expected products 6f-i,o in good yields. Though the exact nature of the
such effect remains unknown, the ability of the phosphine to improve the efficiency of photoredox
reactions has been noted earlier.8b,c,9 Presumably, the role of phosphine is to negate the deleterious
effect of oxygen on photocatalyst performance.
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Table 2. Reactions of 2-Mercaptothiazolinium Salts
MeOTf (1.2 equiv)
DCE, 70 °C, 15 min
N
S
RS
OSiMe3
Me
4
5
(1.3 equiv)
Ar
O
N
(a) KS
N
8
9
RS
R
Ar
(1.3 equiv)
DMPU (1.2 equiv)
S
S
TfO
8
6
MeCN, 70 °C, 30 min
[Ir(dtbbpy)(bpy)2)]PF6 (0.25%)
CH3CN, blue LED, rt, 18 h
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R
Br
(b) MeOTf (1.2 equiv)
DCE, 70 °C, 15 min
7
Starting
Product
Y, %
93
Starting
Product
Y, %
82a
O
O
S
N
4a
4a
4a
6b
6c
6d
4c
6o
6p
6q
S
Cl
Br
I
Me3Si
CF3
O
O
F3C
S
N
73
75
56
4d
4d
4e
99
71
63
S
F3C
Cl
O
O
F3C
CO2Me
O
O
F
S
F
N
4a
4a
4a
4a
4a
6e
6f
6r
6s
6t
F
F
Br
OMe
S
O
O
S
N
Me
64a
68a
91a
81a
4f
7a
7b
7c
80
70
46
41
S
Br
O
O
6g
6h
6i
Br
CN
CO2Me
CF3
O
O
O
O
Br
6u
6v
O
2
2
O
O
O
Br
O
O
O
EtO
EtO
Br
Br
4a
4b
6j
53
85
7d
7e
6w
6x
75
38
O
O
O
S
N
6k
S
Br
O
O
O
Br
EtO
EtO
EtO
EtO
3
4b
4c
4c
6l
6m
6n
68
77
58
7f
7g
7h
6y
6z
6α
57
57
71
3
O
O
CO2Me
O
O
Br
Me3Si
S
N
4
4
S
O
O
O
O
Me3Si
Me3Si
Cl
Br
O
3
O
O
3
Br
aIr(ppy)3 instead of [Ir(dtbbpy)(ppy)2]PF6. Ph3P (0.2 equiv) was added.
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2-Mercaptothiazoline derivatives 4 may be easily synthesized by different pathways, which
greatly increase their applicability. We showed two examples of such transformations involving
hydrothiolation of the double bond and tosylation/substitution of the hydroxy group (Scheme 2).
These reactions starting from cyclohexene and (tetrahydrofuran-2-yl)methanol furnished thiazolines
4 in good yields, which were coupled with a silyl enol ether. Overall, this process may be
considered as a method for the generation of radicals from alkenes or alcohols. The double bond
addition reaction was also used to obtain thiazoline 4i containing a tertiary substituent at sulfur.
However, attempted generation of the corresponding thiazolinium salt by methylation of 4i with
methyl triflate failed, presumably, owing its facile decomposition.
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Scheme 2. Synthesis and Reactions of 2-Mercaptothiazolines.
HS
N
, TfOH
S
N
S
S
CH2Cl2, 
4g
, 75%
OSiMe3
Ph
O
MeOTf, then
Ph
Ir(III), DMPU, blue LED
6
, 79%
N
S
OH
(a) TsCl, NEt3, CH2Cl2
S
O
KS
N
O
(b)
DMF, 70 °C
4h
, 72%
S
OSiMe3
Ph
O
MeOTf, then
Ph
, 67%
O
Ir(III), DMPU, blue LED
6
HS
N
, TfOH
S
S
N
CH2Cl2, 0 °C to rt
S
4i
, 96%
The photoredox reaction likely proceeds via typical mechanism shown in Scheme 3.
Thiazolinium salt 8 is reduced by photoexcited iridium (III) catalyst to give, after cleavage of the C-
S bond, the free radical. The latter attacks at the double bond of the enol ether followed by
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oxidation of the silyloxy-substituted radical. At the final step, the carbocation expels the silyl group,
4
5
which is trapped by DMPU.10 Several thiazolinium salts (8a,c,f) were characterized in solution by
6
7
13
1H and C NMR. Moreover, salt 8c derived from thiazoline 4c (R = CH2SiMe3) was isolated in
8
9
individual state, and its structure was confirmed by single-crystal X-ray analysis. According to
cyclic voltammetry, the reduction of compound 8c begins at a potential of –0.82 V (vs. SCE, see
Supporting Information for details). The values of oxidative potentials of photoexcited iridium
complexes [Ir(dtbbpy)(ppy)2]PF6 (–0.96 V)11 and Ir(ppy)3 (–1.73 V)11 suggest that the direct
electron transfer between these two species is possible. We also performed Stern-Volmer
experiments to test the interaction of salt 8c with iridium complexes. While 8c quenched the
fluorescence of Ir(ppy)3, no quenching of the fluorescence was observed for Ir[(dtbbpy)(ppy)2]PF6.
The absence of quenching means that the interaction of cationic 8c with cationic iridium
Ir[(dtbbpy)(ppy)2] complex is problematic. In this case, the chain mechanism involving oxidation of
silyloxy-substituted radical by the starting cation 8 may be operative, but the nature of the reaction
initiation and the details of the electron transfer event from the cationic iridium complex are not
clear.
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Scheme 3. Proposed Mechanism.
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Me
S
N
4
5
6
7
8
9
S
OSiMe3
Me
S
N
Ar
R
Me
R
5
S
9
S
N
R
S
OSiMe3
Ir (IV)
8
R
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Ar
8
Ir* (III)
9
SiMe3
O
Ir (III)
R
Ar
h
O
O
Me
Me
N
N
R
Ar
6
SiMe3
Me
O
Me
8c
(R = CH2SiMe3)
N
N
In summary, a method for the photoinduced coupling of 2-mercaptothiazolinium salts, generated
by alkylation of thiazolines, with silyl enol ethers is described. The thiazolinium salts behave as
precursors of free radicals upon single electron reduction. The starting thiazolines can be readily
accessed from corresponding alkyl halides, tosylates or alkenes.
EXPERIMENTAL SECTION
General Methods. Column chromatography was carried out employing silica gel (230−400
mesh). Precoated silica gel plates F254 were used for thin-layer analytical chromatography, and UV
light and/or acidic aq KMnO4 solution was used for visualization. High resolution mass spectra
(HRMS) were measured using electrospray ionization (ESI) and a time-of-flight (TOF) mass
analyzer (Bruker MicrOTOF II). The measurements were done in a positive-ion mode (interface
capillary voltage −4500 V) or in a negative-ion mode (3200 V); the mass ranged from m/z 50 to
m/z 3000. For NMR measurements, a Bruker AM300 spectrometer was used. Fluorescence and
absorption spectra were recorded on a Fluorat-02-Panorama spectrofluorometer (Lumex
Instruments). For irradiation, a strip of light-emitting diodes (SMD2835-120 LED 1M Blue, 12 V,
24W/m, 465 nm) was used. Photo-induced reactions were performed in Duran culture tubes (Roth
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cat. no K248.1, outside diameter = 12 mm); the distance from light source to the reaction vessel was
5 mm; during irradiation, the tube was cooled with room temperature water. 2-Mercaptothiazoline,
acetophenones, compounds 7a and 7c-e were purchased from Acros. Compounds 2-
(cyclopentylthio)-1,3-benzothiazole 1,12 2-(methylthio)-4,5-dihydro-1,3-thiazole 4f,13 silyl enol
ethers 5,14 2-bromoethyl acetate 7b,15 ethyl 4-bromobutanoate 7f,16 ethyl 5-bromopentanoate 7g,17
3-bromopropyl benzoate 7h18 were prepared according to literature procedures.
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Potassium 4,5-dihydrothiazole-2-thiolate. Potassium hydroxide (4.48 g, 80.0 mmol) was added to a
stirred solution of 2-mercaptothiazoline (10.0 g, 84.0 mmol) in ethanol (20 mL) at room
temperature. The resulting suspension was stirred until complete dissolution of solid components
(about 0.5 h; mild heating of the reaction mixture was observed; however, no temperature control
was used). The solvent was evaporated under vacuum, the residue was dissolved in a small amount
of methanol (5 mL) under reflux, and the hot solution was quickly diluted with boiling isopropanol
(30 mL). The stirring was immediately discontinued, and the mixture was left to crystallize
overnight at room temperature. The crystals were filtered and dried. Yield 11.52 g (77%). White
crystals. Mp 193 – 195 °C. 1H NMR (300 MHz, DMSO-d6): δ 3.84 (t, J = 7.7 Hz, 1H), 3.02 (t, J =
7.7 Hz, 1H). 13C{1H} NMR (75 MHz, DMSO-d6): δ 177.7, 64.4, 35.7. HRMS (ESI): calcd for
C3H6NS2 [Anion + 2H+], 119.9934; found, 119.9936.
Cyclopentyl pyrrolidine-1-carbodithioate (2). Cyclopentyl bromide (536 µL, 5.0 mmol) was added
to a stirred solution of potassium pyrrolidine-1-carbodithioate (971 mg, 5.25 mmol) in DMF (5 mL)
at room temperature. The resulting white suspension was stirred overnight, then diluted with water
(15 mL), and extracted with hexane (35 mL). The combined organic phases were dried over
Na2SO4, concentrated under reduced pressure, and the residue was crystallized from hexane (2 mL)
at –20 °C. Yield 753 mg (70%). Pale-yellow crystals. Mp 45 – 47 °C. 1H NMR (300 MHz, CDCl3):
δ 4.22 – 4.08 (m, 1H), 3.90 (t, J = 6.7 Hz, 2H), 3.59 (t, J = 6.7 Hz, 2H), 2.32 – 2.13 (m, 2H), 2.05
13
(tt, J = 7.8, 6.7 Hz, 2H), 1.95 (tt, J = 7.8, 6.7 Hz, 2H), 1.79 – 1.54 (m, 6H). C{1H} NMR (75
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MHz, CDCl3): δ 193.4, 54.6, 50.6, 49.4, 33.0, 26.1, 24.9, 24.3. HRMS (ESI): calcd for C10H18NS2
[M + H], 216.0875; found, 216.0880.
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2-(Сyclopentylthio)-1-methyl-1H-imidazole (3). 1-Methyl-1H-imidazole-2-thiol (1.2 g, 10.5 mmol)
was added to a stirred solution of potassium tert-butoxide (1.18 g, 10.5 mmol) in DMF (10 mL) [the
addition was performed at such a rate to maintain the reaction temperature below 30 °C]. Then,
cyclopentyl bromide (1.07 mL, 10.0 mmol) was added slowly and the resulting suspension was
stirred for 4 hours at 70 °C (water bath). The mixture was diluted with water (20 mL) and extracted
with hexane (3×10 mL). The combined organic phases were dried over Na2SO4, concentrated under
reduced pressure, and the residue was distilled under vacuum (10 Torr) using Hickman distilling
head (180 – 200 °C bath temp.). Yield 546 mg (30%). Colorless oil. 1H NMR (300 MHz, CDCl3): δ
7.00 (d, J = 0.9 Hz, 1H), 6.87 (d, J = 0.9 Hz, 1H), 3.71 – 3.60 (m, 1H), 3.58 (s, 3H), 2.05 – 1.89 (m,
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2H), 1.80 – 1.64 (m, 2H), 1.62 – 1.46 (m, 4H). C{1H} NMR (75 MHz, CDCl3): δ 141.8, 129.2,
122.0, 47.6, 33.5, 33.3, 24.4. HRMS (ESI): calcd for C9H15N2S [M + H], 183.0950; found,
183.0951.
2-(Cyclopentylthio)-4,5-dihydrothiazole (4a). Potassium hydroxide (2.26 g, 40.3 mmol) was rapidly
added to a stirred solution of 2-mercaptothiazoline (4.79 g, 40.3 mmol) in ethanol (20 mL), and the
resulting suspension was stirred until complete dissolution of solid components (about 0.5 h). Then,
cyclopentyl bromide (3.4 mL, 33.6 mmol) was added and the mixture was refluxed for 1 hour
(water bath). The mixture was cooled to room temperature, diluted with water (30 mL) and
extracted with MTBE (310 mL). The combined organic phases were dried over Na2SO4,
concentrated under reduced pressure, and the residue was distilled under vacuum (10 Torr) using
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Hickman distilling head (180 – 200 °C bath temp.). Yield 4.83 g (77%). Yellowish oil. H NMR
(300 MHz, CDCl3): δ 4.21 (t, J = 8.0 Hz, 2H), 3.81 (sept, J = 6.8 Hz, 1H), 3.34 (t, J = 8.0 Hz, 2H),
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1.37 (d, J = 6.8 Hz, 6H). C{1H} NMR (75 MHz, CDCl3) δ 165.7, 64.5, 45.7, 35.1, 33.6, 24.6.
HRMS (ESI): calcd for C8H14NS2 [M + H], 188.0562; found, 188.0562.
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Synthesis of 2-mercaptothiazoline derivatives 4b-e (General Procedure I). Alkyl halide (6 mmol) to
a stirred suspension of 2-mercaptothiazoline potassium salt (1.22 g, 7.8 mmol) in acetonitrile (6
mL) was added [a quaternary ammonium salt was also added for the synthesis of 4c,e: for 4c,
Bu4NBr (97 mg, 0.3 mmol); for 4e, Bu4NI (111 mg, 0.3 mmol)]. The mixture was stirred in a closed
vial at 75 °C (water bath), and the reaction progress was monitored by GC analysis. After
completion (1-3 hours), the solvent was evaporated under reduced pressure, the residue was diluted
with water (10 mL) and extracted with hexane (35 mL). The combined organic phases were
filtered through a small pad of Na2SO4, concentrated under reduced pressure, and the residue was
distilled under vacuum (10 Torr) using Hickman distilling head (140 – 170 °C bath temp.).
2-(Isopropylthio)-4,5-dihydrothiazole (4b). Synthesized according to General Procedure I from
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isopropyl bromide. Yield 705 mg (73%). Colorless oil. H NMR (300 MHz, CDCl3): δ 4.21 (t, J =
8.0 Hz, 1H), 3.81 (sept, J = 6.8 Hz, 1H), 3.34 (t, J = 8.0 Hz, 1H), 1.37 (d, J = 6.8 Hz, 1H). 13C{1H}
NMR (75 MHz, CDCl3): δ 165.2, 64.5, 38.2, 35.0, 23.2. HRMS (ESI): calcd for C9H12NS2 [M + H],
162.0406; found, 162.0402.
2-{[(Trimethylsilyl)methyl]thio}-4,5-dihydrothiazole (4c). Synthesized according to General
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Procedure I from (bromomethyl)trimethylsilane. Yield 1.03 g (84%). Colorless oil. H NMR (300
MHz, CDCl3): δ 4.17 (t, J = 7.9 Hz, 2H), 3.37 (t, J = 7.9 Hz, 2H), 2.36 (s, 2H), 0.09 (s, 9H).
13C{1H} NMR (75 MHz, CDCl3): δ 168.1, 64.2, 35.8, 18.2, -1.8. HRMS (ESI): calcd for
C7H16NS2Si [M + H], 206.0488; found, 206.0487.
2-[(2,2,2-Trifluoroethyl)thio]-4,5-dihydrothiazole (4d). Synthesized according to General Procedure
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I from 1,1,1-trifluoro-2-iodoethane. Yield 856 mg (71%). Colorless oil. H NMR (300 MHz,
CDCl3): δ 4.21 (t, J = 8.0 Hz, 1H), 3.87 (q, J = 9.8 Hz, 1H), 3.47 (t, J = 8.0 Hz, 1H). 13C{1H} NMR
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(75 MHz, CDCl3): δ 162.7, 124.77 (q, J = 276.1 Hz), 63.7, 36.4, 33.6 (q, J = 34.2 Hz). F NMR
(282 MHz, CDCl3): -66.55 (t, J = 9.5 Hz). HRMS (ESI): calcd for C5H7F3NS2 [M + H], 201.9967;
found, 201.9960.
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2-[(2,2-Difluoroethyl)thio]-4,5-dihydrothiazole (4e). Synthesized according to General Procedure I
from 1,1-difluoro-2-iodoethane. Yield 889 mg (81%). Colorless oil. 1H NMR (300 MHz, CDCl3) δ
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6.00 (tt, J = 56.7, 4.4 Hz, 1H), 4.19 (t, J = 8.0 Hz, 2H), 3.58 – 3.34 (m, 4H). C{1H} NMR (75
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MHz, CDCl3): δ 163.7, 114.3 (t, J = 242.3 Hz), 63.9, 36.2, 34.5 (t, J = 25.9 Hz). F NMR (282
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MHz, CDCl3): δ -115.59 (dt, J = 56.8, 14.8 Hz). HRMS (ESI): calcd for C5H8F2NS2 [M + H],
184.0061; found, 184.0059.
2-(Cyclohexylthio)-4,5-dihydrothiazole (4g). Cyclohexene (505 µL, 5.0 mmol) and triflic acid (441
µL, 5.0 mmol) were added to a stirred solution of 2-mercaptothiazoline (714 mg, 6.0 mmol) in
CH2Cl2 (3 mL) at room temperature. The mixture was refluxed for 48 hours (heating mantle), then
immersed in a water bath at room temperature and quenched by dropwise addition of saturated aq.
NaHCO3 solution. The organic layer was separated, and the aqueous layer was extracted with
hexane (25 mL). The combined organic phases were filtered through a small pad of Na2SO4,
concentrated under reduced pressure, and the residue was purified by column chromatography.
Yield 753 mg (75 %). Colorless oil. Chromatography: hexanes/EtOAc, 4/1. Rf
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(hexanes/EtOAc, 4/1). 1H NMR (300 MHz, CDCl3): δ 4.20 (t, J = 7.9 Hz, 2H), 3.74 – 3.60 (m, 1H),
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3.33 (t, J = 7.9 Hz, 2H), 2.14 – 1.99 (m, 2H), 1.79 – 1.65 (m, 2H), 1.64 – 1.18 (m, 6H). C{1H}
NMR (75 MHz, CDCl3): δ 165.1, 64.5, 46.0, 35.0, 33.3, 25.8, 25.6. HRMS (ESI): calcd for
C9H16NS2 [M + H], 202.0719; found, 202.0715.
2-{[(Tetrahydrofuran-2-yl)methyl]thio}-4,5-dihydrothiazole (4h). Triethylamine (1.0 ml, 7.2 mmol)
and (tetrahydrofuran-2-yl)methanol (581 µL, 6.0 mmol) were added successively to a stirred
suspension of 4-methylbenzenesulfonyl chloride (1.24 g, 6.5 mmol) in CH2Cl2 (6 mL) at 0 °C. The
cooling bath was removed, the reaction vessel was left to warm to room temperature, and the
resulting homogenous mixture was stirred overnight. After the completion (monitored by GC
analysis), the mixture was diluted with water (10 mL) and extracted with CH2Cl2 (35 mL). The
combined organic phases were dried over Na2SO4 and concentrated under reduced pressure. The
residue was dissolved in DMF (4 mL) and charged with 2-mercaptothiazoline potassium salt (1.26
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g, 8.0 mmol). The resulting suspension was stirred for 3 hours at 70 °C (water bath), then diluted
with water (10 mL) and extracted with hexane (3×5 mL). The combined organic phases were dried
over Na2SO4 and concentrated under reduced pressure. The residue was purified by column
chromatography. Yield 877 mg (72%). Pale-yellow oil. Chromatography: hexanes/EtOAc, 2/1. Rf
0.21 (hexanes/EtOAc, 2/1). 1H NMR (300 MHz, CDCl3): δ 4.22 – 4.06 (m, 3H), 3.86 (dd, J = 14.2,
7.4 Hz, 1H), 3.73 (dd, J = 14.2, 7.6 Hz, 1H), 3.40 – 3.17 (m, 4H), 2.10 – 1.95 (m, 1H), 1.97 – 1.78
(m, 2H), 1.69 – 1.55 (m, 1H). 13C{1H} NMR (75 MHz, CDCl3) δ 165.5, 77.3, 68.3, 64.1, 37.4, 35.6,
30.7, 25.8. HRMS (ESI): calcd for C8H14NOS2 [M + H], 204.0511; found, 204.0513.
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2-[(2,4,4-Trimethylpentan-2-yl)thio]-4,5-dihydrothiazole (4i). 2,4,4-Trimethylpent-1-ene (633 µL,
4.0 mmol) was added dropwise to a stirred solution of 2-mercaptothiazoline (571 mg, 4.8 mmol)
and TfOH (354 µL, 4.0 mmol) in CH2Cl2 (2 mL) at 0 °C. The reaction mixture was stirred for 20
minutes at 0 °C, then warmed to room temperature and kept for additional 10 minutes. The resulting
mixture was quenched with saturated aqueous NaHCO3 (7 mL), then the organic layer was
separated, and the aqueous layer was washed with methyl tert-butyl ether (2×5 mL). The combined
organic phases were filtered through Na2SO4, concentrated under reduced pressure, and the residue
was filtered through a pad of silica gel (~ 3 cm) eluting with hexane/ethyl acetate (6/1). Yield 887
mg (96%). Colorless oil. Rf 0.47 (hexanes/EtOAc, 6/1). 1H NMR (300 MHz, CDCl3): δ 4.26 (t, J =
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7.6 Hz, 2H), 3.25 (t, J = 7.6 Hz, 2H), 1.89 (s, 2H), 1.64 (s, 6H), 1.04 (s, 9H). C{1H} NMR (75
MHz, CDCl3): δ 163.9, 65.3, 54.8, 54.0, 34.1, 32.8, 31.7, 30.3. HRMS (ESI): calcd for
C11H21NS2Na [M + Na], 254.1008; found, 254.1000.
Reaction of 2-mercaptothiazolines 4 (General Procedure II). 2-Mercaptothiazoline 4 (1.0 mmol)
was placed into a sealed tube and diluted with dichloroethane (100 µL). Then, methyl triflate (131
µL, 1.2 mmol) was added at room temperature. The resulting viscous mixture was stirred for 15
minutes at 70 °C (water bath), then cooled down to room temperature, and volatile components
were evaporated under vacuum. The residue was diluted with acetonitrile (1.5 mL), then DMPU
(144 µL, 1.2 mmol), silyl enol ether 5 (1.33 mmol), a photocatalyst [for 6a-e,j-n,p-s,
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Ir(dtbbpy)(ppy)2]PF6 (2.4 mg, 0.25 mol %); for 6f-i,o, Ir(ppy)3 (1.6 mg, 0.25 mol %) and
triphenylphosphine (52.0 mg, 0.2 mmol)] were successively added. The reaction tube was cooled to
–20 °C, and a vacuum of 10 Torr was briefly applied with intense stirring followed by filling with
argon (three times), and the tube was warmed to room temperature. The mixture was irradiated with
blue LEDs upon for 16 hours while maintaining the reaction temperature around 20 C. The
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mixture was diluted with water (10 mL) and extracted with hexane (35 mL). The combined
organic phases were filtered through a small pad of Na2SO4, concentrated under reduced pressure,
and the residue was purified by column chromatography.
2-Cyclopentyl-1-phenylethan-1-one (6a).19 General Procedure II. Yield 154 mg (82%). Slightly-
yellow oil. Chromatography: hexanes/EtOAc, 40/1. Rf 0.27 (hexanes/EtOAc, 40/1). 1H NMR (300
MHz, CDCl3): δ 8.00 – 7.93 (m, J = 5.3, 3.4 Hz, 2H), 7.56 – 7.50 (m, 1H), 7.50 – 7.40 (m, 2H),
2.98 (d, J = 7.1 Hz, 2H), 2.39 (tp, J = 8.3, 7.3 Hz, 1H), 1.96 – 1.78 (m, 2H), 1.72 – 1.48 (m, 4H),
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1.28 – 1.11 (m, 2H). C{1H} NMR (75 MHz, CDCl3): δ 200.3, 137.3, 132.8, 128.5, 128.1, 44.8,
36.1, 32.8, 25.0.
1-(4-Chlorophenyl)-2-cyclopentylethan-1-one (6b). General Procedure II. Yield 207 mg (93%).
White crystals. Mp 63 – 64 °C. Chromatography: hexanes/EtOAc, 30/1. Rf 0.19 (hexanes/EtOAc,
30/1). 1H NMR (300 MHz, CDCl3): δ 7.89 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 8.6 Hz, 2H), 2.95 (d, J =
7.2 Hz, 2H), 2.36 (tp, J = 8.6, 7.2 Hz, 1H), 1.95 – 1.79 (m, 2H), 1.75 – 1.46 (m, 4H), 1.28 – 1.07
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(m, 2H). C{1H} NMR (75 MHz, CDCl3): δ 199.1, 139.3, 135.6, 129.6, 128.9, 44.8, 36.1, 32.8,
25.0. HRMS (ESI): calcd for C13H16ClO [M + H], 223.0884; found, 223.0891.
1-(4-Bromophenyl)-2-cyclopentylethan-1-one (6c). General Procedure II. Yield 195 mg (73%).
Colorless crystals. Mp 69 – 70 °C. Chromatography: hexanes/EtOAc, 20/1. Rf
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(hexanes/EtOAc, 20/1). H NMR (300 MHz, CDCl3): δ 7.81 (d, J = 8.5 Hz, 2H), 7.58 (d, J = 8.5
Hz, 2H), 2.94 (d, J = 7.3 Hz, 2H), 2.36 (tp, J = 8.6, 7.3 Hz, 1H), 1.97 – 1.76 (m, 2H), 1.73 – 1.46
(m, 4H), 1.28 – 1.07 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3): δ 199.3, 136.0, 131.9, 129.7, 128.0,
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2-Cyclopentyl-1-(4-iodophenyl)ethan-1-one (6d). General Procedure II. Yield 238 mg (75%). White
crystals. Mp 66 – 67 °C. Chromatography: hexanes/EtOAc, 30/1. Rf 0.24 (hexanes/EtOAc, 30/1).
1H NMR (300 MHz, CDCl3): δ 7.82 (d, J = 8.5 Hz, 2H), 7.66 (d, J = 8.5 Hz, 2H), 2.93 (d, J = 7.2
Hz, 2H), 2.36 (tp, J = 8.5, 7.2 Hz, 1H), 1.95 – 1.79 (m, 2H), 1.73 – 1.46 (m, 4H), 1.26 – 1.07 (m,
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2H). C{1H} NMR (75 MHz, CDCl3): δ 199.6, 137.9, 136.6, 129.6, 100.8, 44.8, 36.1, 32.8, 25.0.
HRMS (ESI): calcd for C13H16IO [M + H], 315.0240; found, 315.0240.
2-Cyclopentyl-1-(4-methoxyphenyl)ethan-1-one (6e).20 General Procedure II. Yield 122 mg (56%).
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Colorless oil. Chromatography: hexanes/EtOAc, 12/1. Rf 0.27 (hexanes/EtOAc, 12/1). H NMR
(300 MHz, CDCl3): δ 7.93 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 8.4 Hz, 2H), 3.83 (s, 4H), 2.89 (d, J =
7.3 Hz, 2H), 2.35 (tp, J = 8.5, 7.3 Hz, 1H), 1.95 – 1.75 (m, 2H), 1.73 – 1.43 (m, 4H), 1.27 – 1.06
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(m, 2H). C{1H} NMR (75 MHz, CDCl3): δ 198.9, 163.3, 130.4, 130.3, 113.6, 55.4, 44.4, 36.3,
32.7, 25.0.
2-Cyclopentyl-1-(naphthalen-2-yl)ethan-1-one (6f). General Procedure II. Yield 152 mg (64%).
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Slightly-yellow oil. Chromatography: hexanes/EtOAc, 25/1. Rf 0.23 (hexanes/EtOAc, 25/1). H
NMR (300 MHz, CDCl3): δ 8.47 (s, 1H), 8.10 – 7.97 (m, 1H), 8.01 – 7.92 (m, 1H), 7.96 – 7.80 (m,
2H), 7.66 – 7.46 (m, 2H), 3.12 (d, J = 7.4 Hz, 2H), 2.47 (sept, J = 7.4 Hz, 1H), 2.02 – 1.86 (m, 2H),
1.78 – 1.50 (m, 3H), 1.34 – 1.16 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3): δ 200.3, 135.5, 134.7,
132.6, 129.7, 129.5, 128.4, 128.3, 127.8, 126.7, 124.0, 44.9, 36.3, 32.8, 25.1. HRMS (ESI): calcd
for C17H19O [M + H], 239.1430; found, 239.1432.
4-(2-Cyclopentylacetyl)benzonitrile (6g). General Procedure II. Yield 145 mg (68%). Colorless
crystals. Mp 57 – 58 °C. Chromatography: hexanes/EtOAc, 10/1. Rf 0.25 (hexanes/EtOAc, 10/1).
1H NMR (300 MHz, CDCl3): δ 8.02 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 2.98 (d, J = 7.3
Hz, 2H), 2.34 (sept, J = 7.3 Hz, 1H), 1.94 – 1.80 (m, 2H), 1.71 – 1.45 (m, 4H), 1.24 – 1.06 (m, 2H).
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13C{1H} NMR (75 MHz, CDCl3): δ 198.8, 140.1, 132.4, 128.5, 117.9, 116.1, 45.0, 35.7, 32.6, 24.9.
HRMS (ESI): calcd for C14H15NONa [M + Na], 236.1046; found, 236.1046.
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Methyl 4-(2-cyclopentylacetyl)benzoate (6h). General Procedure II. Yield 224 mg (91%). White
crystals. Mp 67 – 68 °C. Chromatography: hexanes/EtOAc, 10/1. Rf 0.25 (hexanes/EtOAc, 10/1).
1H NMR (300 MHz, CDCl3): δ 8.09 (d, J = 8.4 Hz, 2H), 7.97 (d, J = 8.4 Hz, 2H), 3.92 (s, 3H), 2.99
(d, J = 7.2 Hz, 2H), 2.36 (tp, J = 8.6, 7.2 Hz, 1H), 1.95 – 1.79 (m, 2H), 1.72 – 1.45 (m, 4H), 1.29 –
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1.07 (m, 2H). C{1H} NMR (75 MHz, CDCl3): δ 199.8, 166.2, 140.5, 133.7, 129.8, 128.0, 52.4,
45.2, 35.9, 32.7, 25.0. HRMS (ESI): calcd for C15H19O3 [M + H], 247.1329; found, 247.1335.
2-Cyclopentyl-1-(4-(trifluoromethyl)phenyl)ethan-1-one (6i). General Procedure II. Yield 207 mg
(81%). Colorless crystals. Mp 34 – 35 °C. Chromatography: hexanes/EtOAc, 20/1. Rf 0.27
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(hexanes/EtOAc, 20/1). H NMR (300 MHz, CDCl3): δ 8.05 (d, J = 8.1 Hz, 2H), 7.72 (d, J = 8.2
Hz, 2H), 3.01 (d, J = 7.1 Hz, 2H), 2.39 (sept, J = 7.6 Hz, 1H), 1.97 – 1.81 (m, 2H), 1.75 – 1.48 (m,
4H), 1.27 – 1.10 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3): δ 199.3, 140.0, 134.0 (q, J = 32.6 Hz),
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128.5, 125.7 (q, J = 3.7 Hz), 123.7 (q, J = 273.2 Hz), 45.2, 36.0, 32.8, 25.0. F NMR (282 MHz,
Chloroform-d): δ -63.91. HRMS (ESI): calcd for C14H15F3ONa [M + Na], 279.0967; found,
279.0965.
2-Cyclopentyl-1-(2,4-dimethylphenyl)ethan-1-one (6j). General Procedure II. Yield 114 mg (53%).
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Colorless oil. Chromatography: hexanes/EtOAc, 15/1. Rf 0.27 (hexanes/EtOAc, 15/1). H NMR
(300 MHz, CDCl3): δ 7.56 (d, J = 8.3 Hz, 1H), 7.05 (d, J = 5.7 Hz, 2H), 2.90 (d, J = 7.2 Hz, 2H),
2.49 (s, 3H), 2.35 (s, 3H), 2.34 – 2.28 (m, 1H), 1.93 – 1.78 (m, 2H), 1.71 – 1.47 (m, 4H), 1.26 –
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1.09 (m, 2H). C{1H} NMR (75 MHz, CDCl3): δ 204.1, 141.5, 138.3, 135.6, 132.8, 128.9, 126.2,
47.7, 36.3, 32.7, 25.0, 21.4, 21.3. HRMS (ESI): calcd for C15H21O [M + H], 217.1587; found,
217.1589.
1-(4-Bromophenyl)-3-methylbutan-1-one (6k). General Procedure II. Yield 204 mg (85%).
Colorless crystals. Mp 48 – 49 °C. Chromatography: hexanes/EtOAc, 40/1. Rf
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(hexanes/EtOAc, 40/1). H NMR (300 MHz, CDCl3): δ 7.80 (d, J = 8.5 Hz, 2H), 7.58 (d, J = 8.5
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Hz, 2H), 2.79 (d, J = 6.8 Hz, 2H), 2.27 (m, J = 6.8 Hz, 1H), 0.99 (d, J = 6.8 Hz, 6H). 13C NMR (75
MHz, CDCl3): δ 199.1, 136.1, 131.9, 129.7, 128.0, 47.5, 25.2, 22.8. HRMS (ESI): calcd for
C11H1479BrO [M + H], 241.0223; found, 241.0227; calcd for C11H1481BrO [M + H], 243.0202;
found, 243.0208.
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Methyl 4-(3-methylbutanoyl)benzoate (6l).21 General Procedure II. Yield 150 mg (68%). White
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solid. Mp 37 – 38 °C. Chromatography: hexanes/EtOAc, 10/1. Rf 0.25 (hexanes/EtOAc, 10/1). H
NMR (300 MHz, CDCl3): δ 8.03 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 8.4 Hz, 2H), 3.87 (s, 3H), 2.79 (d,
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J = 6.7 Hz, 2H), 2.23 (nonet, J = 6.7 Hz, 1H), 0.93 (d, J = 6.7 Hz, 6H). C{1H} NMR (75 MHz,
CDCl3): δ 199.4, 166.1, 140.5, 133.6, 129.7, 127.8, 52.3, 47.6, 24.9, 22.6.
1-(4-Chlorophenyl)-3-(trimethylsilyl)propan-1-one (6m).22 General Procedure II. Yield 185 mg
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(77%). Yellowish oil. Chromatography: hexanes/EtOAc, 30/1. Rf 0.22 (hexanes/EtOAc, 30/1). H
NMR (300 MHz, CDCl3): δ 7.89 (d, J = 8.6 Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H), 2.97 – 2.85 (m, 2H),
13
0.97 – 0.85 (m, 2H), 0.05 (s, 9H). C{1H} NMR (75 MHz, CDCl3): δ 200.0, 139.3, 135.2, 129.6,
128.9, 33.2, 10.9, -1.7.
1-(4-Bromophenyl)-3-(trimethylsilyl)propan-1-one (6n).22 General Procedure II. Yiled 165 mg
(58%). Slightly-yellow solid. Mp 23 – 24 °C. Chromatography: hexanes/EtOAc, 40/1. Rf 0.28
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(hexanes/EtOAc, 40/1). H NMR (300 MHz, CDCl3): δ 7.78 (d, J = 8.5 Hz, 2H), 7.55 (d, J = 8.5
Hz, 2H), 2.94 – 2.82 (m, 2H), 0.93 – 0.81 (m, 2H), 0.03 (s, 9H). 13C{1H} NMR (75 MHz, CDCl3): δ
200.0, 135.5, 131.8, 129.6, 127.8, 33.1, 10.8, -1.7.
1-(4-(Trifluoromethyl)phenyl)-3-(trimethylsilyl)propan-1-one (6o).22 General Procedure II. Yield
225 mg (82%). Colorless oil. Chromatography: hexanes/EtOAc, 25/1. Rf 0.27 (hexanes/EtOAc,
25/1). 1H NMR (300 MHz, CDCl3): δ 8.04 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 8.2 Hz, 2H), 3.02 – 2.90
(m, 2H), 0.97 – 0.84 (m, 2H), 0.05 (s, 9H). 13C{1H} NMR (75 MHz, CDCl3): δ 200.1, 139.6, 134.2
(q, J = 32.5 Hz), 125.7 (q, J = 3.8 Hz), 123.7 (q, J = 271.1 Hz), 33.6, 10.8, -1.8.
1-(4-Chlorophenyl)-4,4,4-trifluorobutan-1-one (6p).23 General Procedure II. Yield 234 mg (99%).
White solid. Mp 66 – 67 °C. Chromatography: hexanes/EtOAc, 20/1. Rf 0.21 (hexanes/EtOAc,
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20/1). 1H NMR (300 MHz, CDCl3): δ 7.91 (d, J = 8.6 Hz, 2H), 7.46 (d, J = 8.6 Hz, 2H), 3.29 – 3.15
(m, 2H), 2.59 (qt, J = 10.8, 8.1 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 195.1, 140.2, 134.5, 129.5,
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129.2, 127.1 (q, J = 275.7 Hz), 31.3 (q, J = 2.6 Hz), 28.3 (q, J = 29.9 Hz). F{1H} NMR (282
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Methyl 4-(4,4,4-trifluorobutanoyl)benzoate (6q).24 General Procedure II. Yield 185 mg (71%).
White crystals. Mp 75 – 77 °C. Chromatography: hexanes/EtOAc, 10/1. Rf 0.28 (hexanes/EtOAc,
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10/1). H NMR (300 MHz, CDCl3): δ 8.13 (d, J = 8.4 Hz, 2H), 8.01 (d, J = 8.4 Hz, 2H), 3.95 (s,
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3H), 3.35 – 3.20 (m, 2H), 2.71 – 2.49 (m, 2H). C{1H} NMR (75 MHz, CDCl3): δ 195.8, 166.1,
139.3, 134.4, 130.0, 128.0, 127.1 (q, J = 276.1 Hz), 52.5, 31.7 (q, J = 2.6 Hz), 28.3 (q, J = 29.8 Hz).
19F NMR (282 MHz, CDCl3): δ -66.46 (t, J = 10.5 Hz).
1-(4-bromophenyl)-4,4-difluorobutan-1-one (6r).23 General Procedure II. Yield 165 mg (63%).
White solid. Mp 29 – 30 °C. Chromatography: hexanes/EtOAc, 12/1. Rf 0.22 (hexanes/EtOAc,
12/1). 1H NMR (300 MHz, CDCl3): δ 7.82 (d, J = 8.1 Hz, 2H), 7.60 (d, J = 8.1 Hz, 2H), 6.01 (tt, J =
57.1, 4.1 Hz, 1H), 3.14 (t, J = 7.2 Hz, 2H), 2.28 (ttd, J = 18.1, 7.2, 4.1 Hz, 2H). 13C{1H} NMR (75
MHz, CDCl3): δ 196.8, 135.1, 132.0, 129.5, 128.6, 116.4 (t, J = 238.8 Hz), 30.8 (t, J = 5.3 Hz), 28.3
(t, J = 22.0 Hz). 19F NMR (282 MHz, CDCl3): δ -117.86 (dt, J = 57.1, 18.1 Hz).
1-(4-Bromophenyl)propan-1-one (6s).25 General Procedure II. Yield 170 mg (80%). White crystals.
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Mp 44 – 45 °C. Chromatography: hexanes/EtOAc, 20/1. Rf 0.25 (hexanes/EtOAc, 20/1). H NMR
(300 MHz, CDCl3): δ 7.77 (d, J = 8.5 Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H), 2.91 (q, J = 7.2 Hz, 2H),
1.17 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ 199.5, 135.5, 131.7, 129.4, 127.9, 31.7,
8.0.
Reaction with primary bromides 7 (General Procedure III). 2-Mercaptothiazoline potassium salt
(209 mg, 1.33 mmol) was added to a stirred solution of bromide 7 (1.0 mmol) in acetonitrile (1
mL), and the suspension was stirred for 30 minutes at 70 °C (water bath). After completion
(monitored by GC), the solvent was evaporated under reduced pressure, the residue was diluted
with water (10 mL) and extracted with hexane (35 mL). The combined organic phases were
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filtered through a small pad of Na2SO4 and concentrated under reduced pressure. Then,
dichloroethane (100 µL) and MeOTf (131 µL, 1.2 mmol) were added. The resulting viscous
mixture was stirred for 15 minutes at 70 °C (water bath), then cooled down to room temperature,
and all the volatile components were evaporated in vacuum. The residue was dissolved in
acetonitrile (1.5 mL), then DMPU (144 µL, 1.2 mmol), silyl enol ether of acetophenone (255 mg,
1.33 mmol) and [Ir(dtbbpy)(ppy)2]PF6 (2.4 mg, 0.25 mol%) were successively added. The reaction
tube was cooled to –20 °C, and a vacuum of 10 Torr was briefly applied with intense stirring
followed by filling with argon (three times), and the tube was warmed to room temperature. The
mixture was irradiated with blue LEDs upon for 16 hours while maintaining the reaction
temperature around 20 C. The mixture was diluted with water (10 mL) and extracted with hexane
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(35 mL). The combined organic phases were filtered through a small pad of Na2SO4, concentrated
under reduced pressure, and the residue was purified by column chromatography.
1,4-Diphenylbutan-1-one (6t).26 General Procedure III. Yield 157 mg (70%). Yellowish solid. Mp
53 – 54 °C. Chromatography: hexanes/EtOAc, 20/1. Rf 0.26 (hexanes/EtOAc, 20/1). 1H NMR (300
MHz, CDCl3): δ 8.03 – 7.94 (m, 2H), 7.63 – 7.54 (m, 1H), 7.54 – 7.44 (m, 2H), 7.39 – 7.21 (m,
5H), 3.03 (t, J = 7.5 Hz, 2H), 2.79 (t, J = 7.5 Hz, 2H), 2.15 (p, J = 7.5, 7.5 Hz, 2H).
13C{1H} NMR (75 MHz, CDCl3): δ 199.9, 141.7, 137.0, 132.9, 128.6, 128.5, 128.4, 128.0, 125.9,
37.6, 35.2, 25.7.
4-Oxo-4-phenylbutyl acetate (6u).27 General Procedure III. Yield 95 mg (46%). Yellowish oil.
Chromatography: hexanes/EtOAc, 1/1. Rf 0.28 (hexanes/EtOAc, 1/1). 1H NMR (300 MHz, CDCl3):
δ 7.97 – 7.90 (m, 2H), 7.57 – 7.49 (m, 1H), 7.47 – 7.39 (m, 2H), 4.15 (t, J = 6.5 Hz, 2H), 3.03 (t, J
= 7.1 Hz, 2H), 2.06 (tt, J = 7.1, 6.5 Hz, 2H), 2.00 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ
198.9, 170.9, 136.8, 133.0, 128.5, 127.9, 63.7, 34.8, 23.2, 20.8.
1-Phenylhex-5-en-1-one (6v).28 General Procedure III. Yield 71 mg (41%). Yellowish oil.
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Chromatography: hexanes/EtOAc, 20/1. Rf 0.27 (hexanes/EtOAc, 20/1). H NMR (300 MHz,
CDCl3): δ 7.96 (dd, J = 7.0, 1.7 Hz, 2H), 7.58 – 7.52 (m, 1H), 7.49 – 7.42 (m, 2H), 5.83 (ddt, J =
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7.4 Hz, 2H), 2.17 (q, J = 7.4 Hz, 2H), 1.86 (p, J = 7.4 Hz, 2H). C NMR (75 MHz, CDCl3): δ
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200.2, 138.1, 137.1, 132.9, 128.6, 128.0, 115.3, 37.7, 33.2, 23.3.
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Ethyl 4-oxo-4-phenylbutanoate (6w).29 General Procedure III. Yield 155 mg (75%). Slightly-yellow
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oil. Chromatography: hexanes/EtOAc, 4/1. Rf 0.30 (hexanes/EtOAc, 4/1). H NMR (300 MHz,
CDCl3): δ 7.92 (d, J = 7.4 Hz, 2H), 7.54 – 7.45 (m, 1H), 7.44 – 7.34 (m, 2H), 4.10 (q, J = 7.1 Hz,
2H), 3.24 (t, J = 6.6 Hz, 2H), 2.69 (t, J = 6.6 Hz, 2H), 1.20 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (75
MHz, CDCl3): δ 197.9, 172.6, 136.4, 133.0, 128.4, 127.8, 60.4, 33.2, 28.1, 14.0.
1,3-Diphenylpropan-1-one (6x).30 General Procedure III. Yield 80 mg (38%). White crystals. Mp
65 – 66 °C. Chromatography: hexanes/EtOAc, 20/1. Rf 0.29 (hexanes/EtOAc, 20/1). 1H NMR (300
MHz, CDCl3): δ 8.03 – 7.97 (m, 2H), 7.62 – 7.54 (m, 1H), 7.53 – 7.44 (m, 2H), 7.38 – 7.21 (m,
5H), 3.34 (t, J = 7.7 Hz, 2H), 3.12 (t, J = 7.7 Hz, 2H). C{1H} NMR (75 MHz, CDCl3): δ 199.1,
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141.3, 136.9, 133.0, 128.6, 128.5, 128.4, 128.0, 126.1, 40.4, 30.2.
Ethyl 6-oxo-6-phenylhexanoate (6y).31 General Procedure III. Yield 133 mg (57%). Colorless
crystals. Mp 20 – 21 °C. Chromatography: hexanes/EtOAc, 10/1. Rf 0.21 (hexanes/EtOAc, 10/1).
1H NMR (300 MHz, CDCl3): δ 7.93 (d, J = 7.3 Hz, 2H), 7.59 – 7.47 (m, 1H), 7.51 – 7.37 (m, 2H),
4.11 (q, J = 7.1 Hz, 2H), 2.97 (t, J = 6.8 Hz, 2H), 2.34 (t, J = 6.9 Hz, 2H), 1.85 – 1.62 (m, 4H), 1.23
(t, J = 7.1 Hz, 3H). C{1H} NMR (75 MHz, CDCl3): δ 199.8, 173.4, 136.9, 132.9, 128.6, 128.0,
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60.2, 38.1, 34.1, 24.6, 23.6, 14.2.
Ethyl 7-oxo-7-phenylheptanoate (6z).32 General Procedure III. Yield 141 mg (57%). Colorless oil.
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Chromatography: hexanes/EtOAc, 10/1. Rf 0.21 (hexanes/EtOAc, 10/1). H NMR (300 MHz,
CDCl3): δ 7.94 (dd, J = 7.2, 1.3 Hz, 2H), 7.60 – 7.48 (m, 1H), 7.44 (dd, J = 8.2, 6.6 Hz, 2H), 4.11
(q, J = 7.1 Hz, 2H), 2.96 (t, J = 7.4 Hz, 2H), 2.31 (t, J = 7.4 Hz, 2H), 1.75 (p, J = 7.4 Hz, 2H), 1.68
(p, J = 7.4 Hz, 2H), 1.48 – 1.35 (m, 2H), 1.24 (t, J = 7.1 Hz, 3H).
13C{1H} NMR (75 MHz, CDCl3): δ 200.1, 173.6, 137.0, 132.9, 128.6, 128.0, 60.2, 38.3, 34.2, 28.8,
24.8, 23.9, 14.3.
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5-Oxo-5-phenylpentyl benzoate (6α).33 General Procedure III. Yield 200 mg (71%). Yellow oil.
Chromatography: hexanes/EtOAc, 4/1. Rf 0.27 (hexanes/EtOAc, 4/1). 1H NMR (300 MHz, CDCl3):
δ 8.04 (d, J = 7.6 Hz, 2H), 7.95 (d, J = 7.5 Hz, 2H), 7.59 – 7.35 (m, 6H), 4.36 (t, J = 5.8 Hz, 2H),
3.04 (t, J = 6.6 Hz, 2H), 1.99 – 1.79 (m, 4H).
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13C{1H} NMR (75 MHz, CDCl3): δ 199.5, 166.4, 136.9, 132.9, 132.8, 130.3, 129.4, 128.5, 128.2,
127.9, 64.5, 37.8, 28.2, 20.7.
2-Cyclohexyl-1-phenylethan-1-one (6β).34 General Procedure III. Yield 159 mg (79%). Colorless
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oil. Chromatography: hexanes/EtOAc, 30/1. Rf 0.20 (hexanes/EtOAc, 30/1). H NMR (300 MHz,
CDCl3): δ 7.93 (dd, J = 7.0, 1.6 Hz, 2H), 7.57 – 7.47 (m, 1H), 7.42 (dd, J = 8.3, 6.6 Hz, 2H), 2.80
(d, J = 6.8 Hz, 2H), 1.97 (ttt, J = 10.5, 6.8, 3.5 Hz, 1H), 1.81 – 1.58 (m, 5H), 1.39 – 0.91 (m, 5H).
13C{1H} NMR (75 MHz, CDCl3): δ 200.0, 137.4, 132.7, 128.4, 128.0, 46.1, 34.4, 33.4, 26.2, 26.1.
1-Phenyl-3-(tetrahydrofuran-2-yl)propan-1-one (6γ).35 General Procedure III. Yield 137 mg (67%).
Colorless oil. Chromatography: hexanes/EtOAc, 6/1. Rf 0.16 (hexanes/EtOAc, 6/1). 1H NMR (300
MHz, CDCl3): δ 8.03 – 7.94 (m, 2H), 7.59 – 7.50 (m, 1H), 7.50 – 7.41 (m, 2H), 3.97 – 3.82 (m,
2H), 3.73 (td, J = 7.7, 6.5 Hz, 1H), 3.18 (ddd, J = 17.2, 9.0, 5.7 Hz, 1H), 3.05 (ddd, J = 17.2, 8.8,
6.3 Hz, 1H), 2.10 – 1.79 (m, 5H), 1.53 (ddd, J = 15.6, 11.7, 7.4 Hz, 1H). 13C{1H} NMR (75 MHz,
CDCl3): δ 200.1, 137.1, 133.0, 128.6, 128.1, 78.5, 67.8, 35.5, 31.5, 30.0, 25.8.
Generation of salts 8a,f. A mixture of thiazoline 4a,f (0.2 mmol) and dichloroethane (50 µL) in
NMR tube was treated with MeOTf (26µL, 0.24 mmol). The tube was heated at 70 °C (water bath)
for 15 minutes, then cooled to room temperature, and all the volatile components were evaporated
under vacuum. The residue was dissolved in CDCl3.
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2-Cyclopentylthio-3-methyl-4,5-dihydro-1,3-thiazol-3-ium triflate 8a. H NMR (300 MHz, CDCl3):
δ 4.51 (t, J = 8.7 Hz, 2H), 3.85 – 3.71 (m, 3H), 3.32 (s, 3H), 2.34 – 2.14 (m, 2H), 1.84 – 1.58 (m,
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6H). C{1H} NMR (75 MHz, CDCl3): δ 190.8, 120.4 (q, J = 320.6 Hz), 61.9, 50.5, 38.4, 33.8,
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3-Methyl-2-methylthio-4,5-dihydro-1,3-thiazol-3-ium triflate 8f. H NMR (300 MHz, CDCl3): δ
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4.44 (t, J = 8.8 Hz, 2H), 3.67 (t, J = 8.8 Hz, 2H), 3.25 (s, 3H), 2.70 (s, 3H). C{1H} NMR (75
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MHz, CDCl3): δ 192.2, 120.3 (q, J = 320.7 Hz), 62.3, 37.9, 30.1, 18.2.
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3-Methyl-2-{[(trimethylsilyl)methyl]thio}-4,5-dihydro-1,3-thiazol-3-ium triflate (8c). Methyl triflate
(131 µL, 1.2 mmol) was added to a stirred mixture of thiazoline 4c (205 mg, 1.0 mmol) and
dichloroethane (100 µL). The resulting viscous solution was stirred for 15 minutes at 70 °C (water
bath), then cooled down to room temperature, and all volatile components were evaporated under
vacuum. The residue was dissolved in chloroform (0.5 mL) and crystallized overnight by slow
diffusion with methyl tert-butyl ether at room temperature. The resulting white crystals were
washed with cold (–20 °C) methyl tert-butyl ether (32 mL) and dried under vacuum. Yield 296 mg
(80 %). Mp 80 – 81 °C. 1H NMR (300 MHz, CDCl3): δ 4.66 (t, J = 8.8 Hz, 2H), 3.82 (t, J = 8.8 Hz,
2H), 3.41 (s, 3H), 2.49 (s, 2H), 0.21 (s, 9H). 13C{1H} NMR (75 MHz, CDCl3): δ 195.3, 63.5, 38.4,
30.4, 22.2, -1.9. HRMS (ESI): calcd for C8H18NS2Si [Cation], 220.0644; found 220.0635.
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ASSOCIATED CONTENT
Supporting Information. CV curve and X-ray structure for 8c and copies of NMR spectra for all
compounds (PDF). Stern-Volmer plots. The Supporting Information is available free of charge on
the ACS Publications website.
AUTHOR INFORMATION
Corresponding Author
* E-mail: adil25@mail.ru
Author Contributions
All authors have given approval to the final version of the manuscript.
ACKNOWLEDGEMENTS
This work was supported by the Russian Foundation for Basic Research (project 16-29-10661).
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REFERENCES
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(1) (a) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Visible Light Photoredox Catalysis with
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5322–5363. (b) Shaw, M. H.; Twilton, J.; MacMillan, D. W. C. Photoredox Catalysis in
Organic Chemistry. J. Org. Chem. 2016, 81, 6898–6926.
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