Photoredox-Catalyzed Deoxygenative Intramolecular Acylation of Biarylcarboxylic Acids: Access to Fluorenones

Article abstract of DOI:10.1021/acs.joc.7b02197

An efficient deoxygenative radical cyclization reaction has been reported for the synthesis of fluorenones by employing various biarylcarboxylic acids via photoredox catalysis. Attractive features of this process include generation of acyl radical, which quickly underdone intramolecular radical cyclization. This method marks the first photocatalytic intramolecular acyl radical coupling for constructing carbon-carbon bond, which further synthesizes the valuable fluorenone products with mild conditions, good yields, and good functional-group compatibility.

Full text of DOI:10.1021/acs.joc.7b02197

Subscriber access provided by PEPPERDINE UNIV
Note
Photoredox-Catalyzed Deoxygenative Intramolecular
Acylation of Biarylcarboxylic Acids: Access to Fluorenones
Rehanguli Ruzi, Muliang Zhang, Keyume Ablajan, and Chengjian Zhu
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 26 Sep 2017
Downloaded from http://pubs.acs.org on September 26, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 13
The Journal of Organic Chemistry
PhotoredoxꢀCatalyzed Deoxygenative Intramolecular Acylation of Biarylcarboxylic Acids: Access to Fluꢀ
orenones
1
2
3
4
5
6
7
8
Rehanguli Ruzi†‡, Muliang Zhang‡, Keyume Ablajan*†, and Chengjian Zhu*‡
† Key Laboratory of Oil & Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, Colꢀ
lege of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046, P.R. China
‡ State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing Universiꢀ
ty, Nanjing 210093, P. R. China
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
*Eꢀmail: cjzhu@nju.edu.cn., *Eꢀmail: ablajan209@hotmail.com.
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the
journal that you are submitting your paper to)
ABSTRACT
An efficient deoxygenative radical cyclization reaction has been reported for the synthesis of fluorenones by emꢀ
ploying various biarylcarboxylic acids via photoredox catalysis. Attractive features of this process include generation
of acyl radical, which quickly underdone intramolecular radical cyclization. This method marks the first photocatalytic
intramolecular acyl radical coupling for constructing carbonꢀcarbon bond, which further synthesize the valuable fluꢀ
orenone products with mild conditions, good yields and good functionalꢀgroup compatibility.
Fluorenones are an important class of fundamental constituents of organic compounds, which have been extensively
used as optoelectronical materials and biologically active molecules.1 More specifically, with the feature of intense
blue photoꢀ and electroluminescence, liquid crystalline properties, 2 study on fluorenones has advanced as a vivid field
of organic chemistry. Consequently, there are several synthetic strategies available for the preparing of fluorenones.
Traditionally, the Friedel−Crafts acylation of biarylcarboxylic acids have often been applied to synthesis of this class of
compounds.3 However, the treatment with a large excess amount of Brønsted acids is inevitable in these transforꢀ
mations, which also produces large volumes of waste products.3a,3d,3e In this context, some other synthetic methods
have been reported for the construction of fluorenone scaffold such as radical cyclization process,4 the oxidation of
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 13
fluorenes5 or fluorenols6 and intramolecular dehydro DielsꢀAlder reactions.7 In addition, transitionꢀmetalꢀcatalyzed
crossꢀcouplings involving CꢀH bond activation has been well developed for the synthesis of fluorenones (Scheme 1).8
However, transitionꢀmetal catalysis usually requires high temperature and harsh reaction conditions, which are incomꢀ
patible with many sensitive functional groups. Due to the aforementioned importance of fluorenones, the availability of
simple and efficient strategy for the direct preparation of fluorenones from biarylcarboxylic acids will continue to have
a significant impact on chemical synthesis.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Metalꢀcatalyzed Intramolecular CꢀH Acylation of Biarylcarboxylic Acids
In recent years, the application of visibleꢀlightꢀinduced photoredox catalysis has emerged as a novel and efficient
tool for activating carboxylic acids.9 In particular, photocatalyzed radical decarboxylative functionalization has garꢀ
nered much interest as an ideal pathway to generate radicals from carboxylic acids. Generally, radical decarboxylation
of carboxylic acids depend on photoꢀinduced oxidation of carboxylates, giving rise to the formation of reactive radical
intermediates after CO2 extrusion, and a series of valuable transformations have been developed using this oxidative
mode under mild conditions.10 However, there remain to be only few reports detailing transformations of carboxylic
acids by singleꢀelectron reduction process. Recently, the visibleꢀlightꢀmediated tandem acylarylation of olefins and
multicomponent 1, 2ꢀacylalkylation of alkenes have been reported by the Wallentin group.11 Meantime, our group also
achieved hydroacylation of olefins by employing carboxylic acids and hydrosilanes through photoredox catalysis.12
Searching for developing more transformation applications for carboxylic acids, we are going on our further study on
acyl radical intermediates produced by a SET reductive process. To the best of our knowledge, current applications of
2
ACS Paragon Plus Environment

Page 3 of 13
The Journal of Organic Chemistry
visibleꢀlightꢀinduced acyl radical reactions are only limited to intermolecular radical addition onto carbonꢀcarbon mulꢀ
tiple bonds, but have not seen for intramolecular coupling. We wondered that 2ꢀaryl acids would produce acyl radical
by a SET reductive process, followed intramolecular addition to the orthoꢀposition aryl CꢀH component, which lead to
the formation of fluorenones (Scheme 1). Herein we described a practical and simple process for synthesis of fluꢀ
orenones from biarylcarboxylic acids via photoredox catalysis.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
To ensure effective intramolecular radical cyclization, we embarked upon this investigation using 2ꢀphenylbenzoic
acid 1a as the model substrate. As a preliminary experiment, 1a was examined in the presence of dimethyl dicarbonate
(DMDC) which made anhydride intermediates obtained, photocatalyst facꢀIr(ppy)3, we observed the formation of the
desired fluorenones in degassed CH3CN (0.1 M) under irradiation visible light from blue LEDs (5 W, λmax = 455 nm)
at room temperature (entry 1). As shown in Table 1, different solvent were tested and strong polar solvent DMF gave
the better result for this reaction (entries 2ꢀ5). Then we screened other bases including organic bases and inorganic
bases in detail, and they show lower efficiency except for 2,6ꢀlutidine (entries 6ꢀ10). The catalysts
Ir(ppy)2(dtbbpy)(PF6)2, Ru(bpy)3Cl2 only delivered traces of product (entries 11ꢀ12), likely because of their high
reduction potential compared to the photocatalyst facꢀIr(ppy)3. Finally, control experiments confirmed the requirement
of a photocatalyst and a light source for this intramolecular radical cyclization reaction (entries 13ꢀ14).
Table 1. Optimization of the Reaction Conditionsa
entry
1
catalyst
base
solvent
CH3CN
Yield(%)b
20
facꢀIr(ppy)3
2,6ꢀ
lutidine
2
3
4
5
facꢀIr(ppy)3
facꢀIr(ppy)3
facꢀIr(ppy)3
facꢀIr(ppy)3
2,6ꢀ
lutidine
DMSO
DMF
40
78
ꢀ
2,6ꢀ
lutidine
2,6ꢀ
lutidine
DCM
DMA
2,6ꢀ
68
lutidine
6
7
8
facꢀIr(ppy)3
facꢀIr(ppy)3
facꢀIr(ppy)3
DABCO
TMEDA
Cs2CO3
DMF
DMF
DMF
10
23
ꢀ
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 13
9
facꢀIr(ppy)3
facꢀIr(ppy)3
Ru(bpy)3Cl2
DIPEA
Na2CO3
DMF
12
35
ꢀ
1
2
3
10
11
DMF
DMF
2,6ꢀ
4
5
lutidine
6
7
8
9
12
13
Ir(ppy)2(dtbbpy)PF
2,6ꢀ
lutidine
DMF
DMF
DMF
ꢀ
ꢀ
ꢀ
6
ꢀ
2,6ꢀ
lutidine
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
14c
facꢀIr(ppy)3
2,6ꢀ
lutidine
aReaction conditions: 1a (0.1 mmol ), base (0.1 mmol, 1.0 equiv), photocatalyst (0.002 mmol, 2.0 mol %), and solvent (2 mL) under argon
atmosphere, irradiation with 5W blue light LEDs at 25 °C for 20 h. bIsolated yields. cThe reaction was performed without light.
With the optimized reaction conditions obtained, we examined a variety of functionalised biarylcarboxylic acids,
and were pleased to find effective for a wide substrate range (Table 2). A series of paraꢀsubstituted aromatics bearing
electronꢀrich groups (methyl, tertꢀbutyl, methoxyl, benzyloxy and thiomethyl) all worked in good yields (2bꢀ2f),
whereas electronꢀdeficient groups (fluoro, chloro and trifloromethyl) afforded moderate yields of fluorenones (2gꢀ2i).
There was no obvious difference in yield when the subsituent was placed in the ortho position for chloro (2j). We next
investigated metaꢀsubstituted aromatics in the form of metaꢀmethyl and metaꢀchloro substrates. The reaction proceeded
in good yield with little regioselectivity between the two isomers 2k and 2l. This outcome is consistent with typical
Pschorr cyclizations of mꢀsubstituted arenes, which rarely demonstrate regioselectivity in the free radical aromatic subꢀ
stitution process.13 More substituted substrate cyclized in a similarly good yield (2m and 2n) to the paraꢀMe or paraꢀ
OMe analog 2b and 2d. Substituents on the aromatic moiety of carboxylic acids were also tolerated. Reactions for the
substrates with electronꢀdeficient fluoro group or electronꢀrich methoxyl group processed well and afforded the correꢀ
sponding products in good yields (2p and 2q).
Table 2.
Scope of Biarylcarboxylic Acidsa,b
4
ACS Paragon Plus Environment

Page 5 of 13
The Journal of Organic Chemistry
O
O
fac-Ir(ppy)3
2,6-lutidine
OH
1
2
3
4
R2
DMDC, DMF
blue LEDs, rt
R1
R1
R2
2
1
5
O
6
O
O
7
8
Me
tBu
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
2a
, 78%
2c
, 85%
O
2b
, 83%
O
O
SMe
OBn
OMe
2e,
72%
2d
7
9%
,
2f,
71%
O
O
O
F
Cl
CF3
2g,
58%
2h,
57%
2i,
54%
O
O
O
Me
*
OMe
*
Cl
2j
, 70%
2k,
84%, r.r. = 7:1
O
2l
, 85%, r.r. = 6:1
O
O
OMe
Me
OMe
Me
2m
, 87%
2n
, 83%
O
2o,
67%
O
F
Me
2p
, 61%
2q
, 86%
aReaction conditions: 1 (0.1 mmol), DMDC (0.3 mmol, 3 equiv), 2,6ꢀlutidine (0.1 mmol, 1.0 equiv), facꢀIr(ppy)3 (0.002 mmol, 2.0 mol %),
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
b
and DMF (2 mL) under argon atmosphere, irradiation with 5W blue LEDs at 25 °C for 20ꢀ24 h. The regioisomeric ratio (r.r.) was deterꢀ
mined by isolated yield.
To demonstrate the synthetic utility of this intramolecular acylation of biarylcarboxylic acids, a gramꢀ scale reaction
was carried out under otherwise standard condition, and the desired fluorenone product 2a was obtained in 72% yield
on 5.0 mmol scale (Scheme 2).
Scheme 2. GramꢀScale Reaction
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 13
1
2
3
4
5
6
7
8
9
To further insight into intramolecular acylation cyclization process, 2.0 equiv of TEMPO was added as an additive,
2,2,6,6ꢀtetramethylpiperidinꢀ1ꢀyl [1,1'ꢀbiphenyl]ꢀ2ꢀcarboxylate 8 was observed in 34% yield, which supported that the
reaction proceeded through a radical pathway (Scheme 3A). The mixed anhydride intermediate 4 could be isolated and
delivered the desired product in presence of photocatalyst (Scheme 3B). Next, we also carried out a kinetic isotope
effect (KIE) experiment to gain more insights into the mechanism. When a 1:1 mixture of 1a and [D5] 1a was subjectꢀ
ed to the photoredox catalyzed deoxygenative intramolecular acylation reaction conditions, the products 2a and [D4] 2a
were obtained in a ratio of 1.31:1 by NMR analysis (Scheme 3C). This KIE value of 1.31 indicated that CꢀH cleavage
was not the first irreversible step in this photoredox cycle.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Mechanistic Experiment
A. Radical Trapping Experiment with TEMPO
N
O
O
O
O
OH
Standard condition
TEMPO (2.0 equiv)
+
2a
1a
0%
8, 34%
O
Me
O
B.
O
O
fac-Ir(ppy)3 (2.0 mol %)
DMF(2 mL), Blue LEDs
rt, 24h
O
2a, 68%
5, 0.1 mmol
C. Intermolecular Kinetic Isotope Effect (KIE)
COOH
O
O
fac-Ir(ppy)3 (2.0 mol %)
2,6-lutidine (1.0 equiv)
DMDC (3.0 equiv), DMF
Blue LEDs, rt, 24h
COOH
1a
+
+
D4
kH/KD = 1.31/1
2a
[D4]2a
D5
[D5]1a
6
ACS Paragon Plus Environment

Page 7 of 13
The Journal of Organic Chemistry
Based on the literature reported and our previous work11,12, a plausible reaction mechanism for intramolecular
1
2
radical cyclization reaction is proposed, as shown in Scheme 4. The anhydride intermediate 3 is quickly produced from
biarylcarboxylic acid 1a and DMDC in the presence of 2,6ꢀlutidine. Under the visibleꢀlight irradiation, the
photocatalyst facꢀIr(ppy)3 goes through a metal to ligand chargeꢀtransfer (MLCT) process to generate the facꢀ
*IrIII(ppy)3. Then a SET step from this strongly reducing excited state species Ir*III to intermediate 4 would generate
the radical anion 5 and IrIV. The radical anion 5, after fragmentation, gives acyl radical 6 along with CO2 and methanoꢀ
ate. Acyl radical 6 undergoes intramolecular addition to the orthoꢀposition of aryl CꢀH component to deliver the
intermediate 7. Subsequently, a second oneꢀelectron oxidation and proton loss from intermediate 7 are required to give
the final product 2a.
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 4. Possible Mechanism
In summary, we have successfully developed a redoxꢀneutral approach for the synthesis of fluorenones by
intramolecular radical cyclization via photoredox catalysis. The protocol presents a mild and energyꢀefficient system
which offers an alternative method for the formation of fluorenones. Attractive features of this process include
generation of acyl radical, which effectively undergoes radical cyclization. Further applications of visibleꢀlightꢀinduced
photoredoxꢀcatalyzed transformation involving carboxylic acids are currently underway in our laboratories.
EXPERIMENTAL SECTION
General Methods. 1H NMR, 13C NMR were recorded using 400 MHz spectrometer at room temperature, with TMS
as internal standard. Chemical shifts (δ) are determined in ppm downfield from tetramethylsilane. HRMS data were
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 13
recorded by a TOF LC/MS. Melting points (mp) were determined with a digital electrothermal apparatus without furꢀ
ther correction. All of other commercially available compounds were used without further purification. Thin Layer
Chromatography (TLC) was used to detect the progress of reactions and to separate products. Biarylcarboxylic acid 1a
was purchased from SigmaꢀAldrich. Other biarylcarboxylic acids 1 were prepared according to the reported proceꢀ
dure.13
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General Procedure for The Intramolecular CꢀH Acylation of Biarylcarboxylic Acid: An ovenꢀdried Schlenk tube
(10 mL) was equipped with a magnetic stir bar, 1 (0.1 mmol) and facꢀIr (ppy) 3 (0.02 equiv, 0.002 mmol, 1.3 mg). The
flask was evacuated and backfilled with Ar for three times, 2.0 mL DMF, 2, 6ꢀlutidine (1.0 equiv, 0.1 mmol, 10.7 mg)
and DMDC (3 equiv, 0.3 mmol, 40.2 mg) were added with syringe under Ar. The tube was placed at a distance (app. 5
cm) from 5W blue LEDs lamb, and the resulting solution was stirred at ambient temperature under visibleꢀlight irradiaꢀ
tion and monitored by TLC. After the reaction was finished, the mixture was concentrated under vacuum to remove
DMF, and the residue was purified by silica gel chromatography (hexane/EtOAc = 20/1ꢀ5/1) to afford the product 2.
1
Fluorenꢀ9ꢀone (2a):8a yellow solid; (14.0 mg, 78%); mp 82ꢀ83 °C; H NMR (400MHz, CDCl3): δ 7.62 (d, J = 7.2
Hz, 2H), 7.42 ꢀ7.48 (m, 4H), 7.24ꢀ7.28 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 193.9, 144.4, 134.7, 134.1, 129.1,
124.3, 120.3. HRMS (APCI) calcd. for C13H9O ([M+H]+): 181.0648, found: 181.0649.
1
2ꢀMethylfluorenꢀ9ꢀone (2b):8a yellow solid; (16.1 mg, 83% ); mp 90ꢀ91 °C; H NMR (400 MHz, CDCl3) δ 7.59 (d, J
= 7.3 Hz, 1H), 7.41ꢀ7.43 (m, 3H), 7.34 (d, J = 7.6 Hz, 1H), 7.20ꢀ7.24 (m, 2H), 2.34 (s, 3 H). 13C NMR (100 MHz,
CDCl3) δ 194.2, 144.6, 141.8, 139.2, 135.1, 134.6, 134.4, 134.2, 128.6, 125.0, 124.2, 120.1, 120.0, 21.4. HRMS
(APCI) calcd. for C14H11O ([M+H]+): 195.0804, found: 195.0806.
2ꢀ(Tertꢀbutyl)ꢀ9Hꢀfluorenꢀ9ꢀone (2c):14 yellow solid;(20 mg, 85%); mp 94ꢀ95 °C; 1H NMR (400 MHz, CDCl3) δ 7.71
(d, J = 1.8 Hz, 1H), 7.62 (d, J = 7.4 Hz, 1H), 7.48ꢀ7.50 (m, 1H), 7.40ꢀ7.45(m, 3H), 7.22ꢀ7.25 (m, 1H), 1.34 (s, 9H).
13C NMR (100 MHz, CDCl3) δ 194.4, 152.8, 144.5, 141.8, 134.6, 134.5, 134.2, 131.5, 128.6, 124.2, 121.6, 120.1,
120.0, 35.1, 31.2. HRMS (APCI) calcd. for C17H17O ([M+H]+): 237.1274, found: 237.1275.
2ꢀMethoxyꢀ9Hꢀfluorenꢀ9ꢀone (2d):8a yellow solid; (16.6 mg, 79%); mp 75ꢀ76 °C; 1H NMR (400 MHz, CDCl3) δ 7.57
(d, J = 7.3 Hz, 1H), 7.34ꢀ7.42 (m, 3H),7.15ꢀ7.19 (m, 2H), 6.93ꢀ6.96 (m, 1H), 3.83 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 193.9, 160.8, 144.9, 136.9, 135.9, 134.8, 134.3, 127.9, 124.3, 121.3, 120.2, 119.6, 109.4, 55.7. HRMS
(APCI) calcd. for C14H11O2 ([M+H]+): 211.0754, found: 211.0754.
1
2ꢀ(Benzyloxy)ꢀ9Hꢀfluorenꢀ9ꢀone (2e): yellow solid; (20.6 mg, 72%); mp 135ꢀ136 °C; H NMR (400 MHz, CDCl3) δ
7.58 (d, J = 7.3 Hz, 1H), 7.33ꢀ7.48 (m, 8H), 7.25 (d, J = 4.2 Hz, 1H), 7.15ꢀ7.19 (m, 1H), 7.01ꢀ7.04 (m, 1H), 5.08 (s,
2H). 13C NMR (100 MHz, CDCl3) δ 193.8, 159.9, 144.8, 137.2 , 136.3, 135.9, 134.9, 134.3, 128.7, 128.2, 127.9,
8
ACS Paragon Plus Environment

Page 9 of 13
The Journal of Organic Chemistry
127.5, 124.3, 121.4, 121.1 , 120.3, 119.6, 118.1, 110.4, 70.4. HRMS (APCI) calcd. for C20H15O2 ([M+H]+): 287.1067,
found: 287.1068.
1
2
3
4
5
6
7
8
9
1
2ꢀ(Methylthio)ꢀ9Hꢀfluorenꢀ9ꢀone (2f): orange solid; (16.0 mg, 71%); mp 115ꢀ116 °C; H NMR (400 MHz, CDCl3) δ
7.60 (d, J = 7.3 Hz, 1H), 7.41ꢀ7.49 (m, 3H), 7.37 (d, J = 7.8 Hz, 1H), 7.29ꢀ7.31 (m, 1H), 7.22ꢀ7.24 (m, 1H), 2.51 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 193.6, 144.4, 141.0, 140.4, 134.9, 134.8, 133.8, 132.0, 128.7, 124.4, 121.6, 120.5,
120.1, 15.7. HRMS (APCI) calcd. for C14H11OS ([M+H]+): 227.0525, found: 227.0526.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀFluoroꢀ9Hꢀfluorenꢀ9ꢀone (2g):8a yellow solid; (11.5 mg, 58%); mp 114ꢀ115 °C; 1H NMR (400 MHz, CDCl3) δ 7.61
(d, J = 7.4 Hz, 1H), 7.41ꢀ7.48 (m, 3H), 7.23ꢀ7.31 (m, 2H), 7.10ꢀ7.15(m, 1H). 13C NMR (100 MHz, CDCl3) δ 192.4,
163.5 (d, JCF = 249 Hz),143.9, 140.1, 136.3, 135.0, 134.3, 128.7, 124.6, 121.6 (d, JCF = 8 Hz,), 120.8 (d, JCF = 23 Hz,),
120.1, 111.9 (d, JCF = 24 Hz). HRMS (APCI) calcd. for C13H8FO ([M+H]+): 199.0554, found: 199.0555.
2ꢀChloroꢀ9Hꢀfluorenꢀ9ꢀone (2h):8a yellow solid; (12.2 mg, 57%); mp 122ꢀ123 °C; 1H NMR (400 MHz, CDCl3) δ 7.66
(d, J = 7.4 Hz, 1H), 7.61 (m, 1H), 7.51ꢀ7.52 (m, 2H), 7.45 (d, J = 1.1Hz, 2H), 7.29ꢀ7.33 (m, 1H). 13C NMR (100 MHz,
CDCl3) δ 192.5, 143.7, 142.6, 135.7, 135.0, 134.7, 134.1, 133.9, 129.3, 124.7, 124.6, 121.4, 120.4. HRMS (APCI)
calcd. for C13H8ClO ([M+H]+): 215.0258, found: 215.0258.
2ꢀTrifluoromethylfluorenꢀ9ꢀone (2i):8a yellow solid; (13.4 mg, 54%); mp 147ꢀ148 °C; 1H NMR (400 MHz, CDCl3) δ
7.86 (s, 1H), 7.68ꢀ7.75 (m, 2H), 7.52ꢀ7.61 (m, 3H), 7.35ꢀ7.39 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 192.1, 147.4,
143.0, 135.1, 134.5, 134.3, 131.6 (q, JCF = 4Hz), 131.3 (q, JCF = 33Hz), 130.2 , 124.7, 123.7 (q, JCF = 271Hz), 121.2 (q,
JCF = 4Hz), 121.1, 120.4. HRMS (APCI) calcd. for C14H8F3O ([M+H]+): 249.0522, found: 249.0524.
4ꢀChloroꢀ9Hꢀfluorenꢀ9ꢀone (2j):8a yellow solid; (15.0 mg, 70%); mp 183ꢀ184 °C; 1H NMR (400 MHz, CDCl3) δ
8.12 (d, J = 7.6 Hz, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.49ꢀ7.57 (m, 2H), 7.40 (d, J = 8.1 Hz, 1H), 7.31ꢀ7.35 (m, 1H),
7.19ꢀ7.23(m, 1H). 13C NMR (100 MHz, CDCl3) δ 192.5, 143.1, 140.6, 136.4, 136.1, 135.0, 134.0, 130.0, 129.6, 129.4,
124.4, 124.1, 122.5. HRMS (APCI) calcd. for C13H8ClO ([M+H]+): 215.0258, found: 215.0259.
1
3ꢀMethylꢀ9Hꢀfluorenꢀ9ꢀone (2k):8a yellow solid; (14.3 mg, 73%); mp 65ꢀ66 °C; H NMR (400 MHz, CDCl3) δ 7.60
(d, J = 7.3 Hz, 1H), 7.50 (d, J = 7.5 Hz, 1H), 7.40ꢀ7.44 (m, 2H), 7.22ꢀ7.27(m, 2H), 7.04 (d, J = 7.5 Hz, 1H), 2.38 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 193.6, 145.8, 144.8, 144.3, 134.7, 134.4, 131.8, 129.6, 128.9, 124.3, 124.1, 121.2,
120.1, 22.2. HRMS (APCI) calcd. for C14H11O ([M+H]+): 195.0804, found: 195.0807.
1ꢀMethylꢀ9Hꢀfluorenꢀ9ꢀone (2kʹ):15 yellow solid; (2.1 mg, 11%); mp 98ꢀ99 °C; 1H NMR (400 MHz, CDCl3) δ 7.63
(d, J = 7.3 Hz, 1H), 7.45ꢀ7.52 (m, 2H), 7.28ꢀ7.37 (m, 3H), 7.05 (d, J = 6.6 Hz, 1H), 2.63 (s, 3H).
3ꢀMethoxyꢀ9Hꢀfluorenꢀ9ꢀone (2l):16 yellow solid; (15.3 mg, 72%); mp 99ꢀ100 °C; 1H NMR (400 MHz, CDCl3) δ 7.58ꢀ
7.61(m, 2H), 7.41ꢀ7.46 (m, 2H), 7.25ꢀ7.30 (m, 1H), 6.99 (d, J = 2.2 Hz, 1H), 6.70ꢀ6.73 (m, 1H), 3.89 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 192.5, 165.4, 147.0, 143.3, 135.3, 134.1, 129.3, 127.1, 126.2, 123.8, 120.1, 113.0, 107.1,
55.8. HRMS (APCI) calcd. for C14H11O2 ([M+H]+): 211.0754, found: 211.0755.
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 13
1ꢀMethoxyꢀ9Hꢀfluorenꢀ9ꢀone (2lʹ):16 yellow solid; (2.7 mg, 13%); mp 138ꢀ139 °C; 1H NMR (400 MHz, CDCl3) δ 7.58
1
2
(d, J = 7.3 Hz, 1H), 7.34ꢀ7.44 (m, 3H), 7.19 –7.24 (m, 2H), 7.07 (d, J = 7.3 Hz, 1H), 6.77 (d, J = 8.5 Hz, 1H), 3.92 (s,
3
4
3H).
5
6
7
8
1,3ꢀDimethyl ꢀ9Hꢀfluorenꢀ9ꢀone (2m):8a yellow solid; (18.1 mg, 87%); mp 111ꢀ112 °C; 1H NMR (400 MHz, CDCl3) δ
7.60 (d, J = 7.3 Hz, 1H), 7.41ꢀ7.46 (m, 2H), 7.24ꢀ7.27 (m, 1H), 7.15 (s, 1H), 6.84 (s, 1H), 2.57 (s, 3 H), 2.36 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 194.7, 145.2, 145.2, 143.8, 139.4, 135.0, 134.1, 132.3, 128.8, 123.7, 119.8, 118.9,
22.0, 17.8. HRMS (APCI) calcd. for C15H13O ([M+H]+): 209.0961, found: 209.0963.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1,3ꢀDimethoxyꢀ9Hꢀfluorenꢀ9ꢀone (2n):17 yellow solid; (20.0 mg, 83%); mp 142ꢀ143 °C; 1H NMR (400 MHz, CDCl3) δ
7.91 (d, J = 7.8 Hz, 1H), 7.52ꢀ7.56 (m, 1H), 7.37ꢀ7.44 (m, 2H), 6.49 (s, 1H), 6.45 (d, J = 4.5 Hz, 1H), 3.79 (s, 6H). 13
C
NMR (100 MHz, CDCl3) δ 172.9, 160.4, 143.0, 142.9, 131.9, 130.9, 130.4, 129.6, 127.4, 123.6, 119.9, 106.8, 99.6,
55.4. HRMS (APCI) calcd. for C15H13O3 ([M+H]+): 241.0859, found: 241.0861.
1
4ꢀMethylfluorenꢀ9ꢀone (2o):8a yellow solid; (15.4 mg, 67%); mp 157ꢀ158 °C; H NMR (400 MHz, CDCl3) δ 8.41 (d, J
= 8.0 Hz, 1H), 7.95 (d, J = 7.6 Hz, 1H), 7.80ꢀ7.84 (m, 1H), 7.68ꢀ7.74 (m, 2H), 7.63ꢀ7.65 (m, 1H), 7.52ꢀ7.59 (m, 2H),
7.46ꢀ7.50 (m, 1H),7.25ꢀ7.29 (m,1H). 13C NMR (100 MHz, CDCl3) δ 194.4, 145.0, 142.8, 138.0, 134.5, 134.4, 131.8,
129.9, 129.6, 128.8, 128.7, 128.2, 127.7, 124.8, 124.0, 123.3, 119.8. HRMS(APCI) calcd. for C17H11O ([M+H]+):
231.0804, found: 231.0805.
2ꢀFluoroꢀ9Hꢀfluorenꢀ9ꢀone (2p):17 yellow solid; (12.1 mg, 61%); mp 116ꢀ117 °C; 1H NMR (400 MHz, CDCl3) δ 7.62
(d, J = 7.4 Hz, 1H), 7.42ꢀ7.48 (m, 3H), 7.23ꢀ7.31 (m, 2H), 7.10ꢀ7.15 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 192.5 ,
163.5 (d, JCF = 249.0Hz), 143.9 , 140.1 , 136.3 , 135.0, 134.3, 128.7 , 124.6, 121.6 (d, JCF = 7.0 Hz), 120.9 (d, JCF= 23
Hz), 120.1, 111.9 (JCF = 23 Hz). HRMS (APCI) calcd. for C13H8FO ([M+H]+): 199.0554, found: 199.0556.
2ꢀMethylꢀ9Hꢀfluorenꢀ9ꢀone (2q):18 yellow solid; (16.7 mg, 86%); mp 125ꢀ126 °C; 1H NMR (400 MHz, CDCl3) δ 7.60
(d, J = 7.3 Hz, 1H), 7.42 (d, J = 4.0 Hz, 3H), 7.35 (d, J = 7.6 Hz, 1H), 7.19ꢀ7.25 (m, 2H), 2.35 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 194.1, 144.6, 141.8, 139.2, 135.1, 134.6, 134.4, 134.3, 128.6, 125.0, 124.2, 120.1, 120.0, 21.4. HRMS
(APCI) calcd. for C14H11O ([M+H]+): 195.0804, found: 195.0805.
Gramꢀscale Reaction Procedure of 2a: An ovenꢀdried Schlenk tube (100 mL) was equipped with a magnetic stir bar,
1a (5.0 mmol) and facꢀIr (ppy) 3 (0.02 equiv, 0.1 mmol, 65 mg). The flask was evacuated and backfilled with Ar for
three times, 60 mL DMF, 2, 6ꢀlutidine (1.0 equiv, 5.0 mmol, and 53.5 mg) and DMDC (3 equiv, 15 mmol, 2.01 g)
were added with syringe under Ar. The tube was placed at a distance (app. 5 cm) from 24W blue LEDs lamb, and the
resulting solution was stirred at ambient temperature under visibleꢀlight irradiation and monitored by TLC. After the
reaction was finished, the mixture was concentrated under vacuum to remove DMF, and the residue was purified by
silica gel chromatography (hexane/EtOAc = 20/1ꢀ5/1) to afford the product 2a (0.65 g, 72%).
General Procedure for Radical Trapping Experiment with TEMPO: An ovenꢀdried Schlenk tube (10 mL) was
equipped with a magnetic stir bar, 1a (0.1 mmol), facꢀIr (ppy) 3 (0.02 equiv, 0.002 mmol, 1.3 mg) and TEMPO (0.2
mmol). The flask was evacuated and backfilled with Ar for three times, 2.0 mL DMF, 2,6ꢀlutidine (1.0 equiv, 0.1 mmol,
10.7 mg) and DMDC (3 equiv, 0.3 mmol, 40.2 mg) were added with syringe under Ar. The tube was placed at a disꢀ
10
ACS Paragon Plus Environment

Page 11 of 13
The Journal of Organic Chemistry
tance (app. 5 cm) from 5W blue LEDs lamb, and the resulting solution was stirred at ambient temperature under visiꢀ
bleꢀlight irradiation and monitored by TLC. After the reaction was finished, the mixture was concentrated under vacuꢀ
um to remove DMF, and the residue was purified by silica gel chromatography (hexane/EtOAc = 20/1ꢀ5/1) to afford
the product 8.
1
2
3
4
5
6
7
8
1
2,6,6ꢀTetramethylpiperidinꢀ1ꢀyl [1,1'ꢀbiphenyl]ꢀ2ꢀcarboxylate (8): colorless liquid (11.5 mg, 34%). H NMR (400
MHz, CDCl3) δ 7.83 (d, J = 7.7 Hz, 1H), 7.50ꢀ7.54 (m, 1H), 7.39ꢀ7.44 (m, 1H), 7.29ꢀ7.37 (m, 6H), 1.55ꢀ1.66 (m, 4H),
1.47 (d, J = 12.4 Hz, 2H), 1.01 (s, 6H), 0.94 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 168.6, 142.5, 141.4, 131.1, 130.9,
130.8, 129.6, 128.74, 128.1, 127.3, 127.1, 60.2, 39.2, 31.9, 20.5, 16.9. HRMS (APCI) calcd. for C22H28NO2 ([M+H]+):
338.2115, found: 338.2116.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Intermolecular Kinetic Isotope Effect (KIE): An ovenꢀdried Schlenk tube (10 mL) was equipped with a magnetic
stir bar, 1a (0.1 mmol), [D5]1a (0.1 mmol) and facꢀIr (ppy)3 (0.02 equiv, 0.002 mmol, 1.3 mg). The flask was evacuatꢀ
ed and backfilled with Ar for three times, 2.0 mL DMF, 2,6ꢀlutidine (1.0 equiv, 0.1 mmol, 10.7 mg) and DMDC (3
equiv, 0.3 mmol, 40.2 mg) were added with syringe under Ar. The tube was placed at a distance (app. 5 cm) from 5W
blue LEDs lamb, and the resulting solution was stirred at ambient temperature under visibleꢀlight irradiation for 24 h.
After the reaction was finished, the mixture was concentrated under vacuum to remove DMF, and the residue was puriꢀ
fied by silica gel chromatography (hexane/EtOAc = 20/1ꢀ5/1) to afford the product. This KIE value was determined by
NMR analysis (KH/KD = 1.31/1).
ASSOCIATED CONTENT
Supporting Information:
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7bxxxxx.
1H and 13C NMR spectra of all compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: cjzhu@nju.edu.cn
*Eꢀmail: ablajan209@hotmail.com
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 13
We gratefully acknowledge the National Natural Science Foundation of China (21474048, 21372114, 21672099 and
21462041).
1
2
3
4
5
6
7
REFERENCE
8
9
(1) (a) Greenlee, M. L.; Laub, J. B.; Rouen, G. P.; DiNinno, F.; Hammond, M. L.; Huber, J. L.; Sundelof, J. G.; Hammond,
G. G. Bioorg. Med. Chem. Lett. 1999, 9, 3225. (b) Perry. P. J.; Read .M. A.; Davies, R. T.; Gowan, S. M.; Reszka, A.
P.; Wood, A. A.; Kelland, L. R.; Neidle, S. J. Med. Chem. 1999, 42, 2679. (c) Tierney, M. T.; Grinstaf, M. W. J. Org.
Chem. 2000, 65, 5355.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2) (a) McCubbin, J. A.; Tong, X. ; Wang, R. Y. ; Zhao, Y.; Snieckus, V. ; Lemieu, R. P. J. Am. Chem. Soc. 2004, 126, 1161.
(b) Shultz, D. A.; Sloop, J. C.; Washington, G. J. Org. Chem. 2006, 71, 9104.
(3) (a) Wade, J. L. G.; Acker, K. J. ; Earl, R. A.; Osteryoung, R. A. J. Org. Chem. 1979, 44, 3724. (b) Coelho, P. J.;
Carvalho, L. M.; Rodrigues, S.; OliveiraꢀCampos, A. M. F.; Dubest, R.; Aubard, J.; Samat,; Guglielmetti, R.
Tetrahedron 2002, 58, 925. (c) Tilly, D.; Samanta, S. S.; Castanet, AꢀS.; Mortier, A De, J. Eur. J. Org. Chem. 2006, 174.
(4) (a) Shi, Z. Z.; Glorius, F. Chem. Sci. 2013, 4, 829. (b) Wertz, S.; Leifert, D. Studer, A. Org. Lett. 2013, 15, 928. (c) Seo,
S.; Slater, M.; Greaney, M. F. Org. Lett. 2012, 14, 2650.
(5) (a) Ghosh, A. K.;. Xu, CꢀX.; Kulkarni, S. S.; Wink, D. Org. Lett. 2005, 7, 263. (b) Catino, A. J.; Nichols, J. M.; Choi,
H.; Gottipamula, S.; Doyle, M. P. Org. Lett. 2005, 7, 5167.
(6) (a) Liu, T. P.; Liao, Y. X.; Xing, C. H.; Hu, Q. S. Org. Lett. 2011, 13, 2452. (b) Bei, X.; Hagemeyer, A.; Volpe, A.; Saxꢀ
ton, R.; Turner, H.; Guram, A. S. J. Org. Chem. 2004, 69, 8626.
(7) (a) Rodríguez, D.; Martı´nezꢀEsperón, M. F.; Va´zquez, A. N.; Castedo, L.; Domínguez, D.; Saa, C. J. Org. Chem. 2004,
69, 3842. (b) Atienza, C.; Mateo, C.; Frutos, O.; Echavarren, A. M. Org. Lett. 2001, 3, 153.
(8) (a) Fukuyama, T.; Maetani, S.; Miyagawa, K.; Ryu, I. Org. Lett. 2014, 16, 3216. (b) Song, J.; Wei, F. l.; Sun, W.; Li, K.;
Tian, Y.; Liu, C.; Li, Y. l.; Xie, L. H. Org. Lett. 2015, 17, 2106. (c) Sun, D. N.; Li, B. J.; Lan, J. B.; Huang, Q.; You, J.
S. Chem. Commun. 2016, 52, 3635.
(9) For selected recent reviews: (a) Xuan, J.; Zhang, Z. G.; Xiao, W. J. Angew. Chem., Int. Ed. 2015, 54, 15632. (b) Huang,
H. C.; Jia, K. F.; Chen, Y. Y.; ACS Catal. 2016, 6, 4983.
(10) For selected visibleꢀlightꢀmediated oxidative decarboxylative functionalization examples: (a) Liu, J.; Liu, Q.; Yi, H.;
Qin, C.; Bai, R. P.; Qi, X. T.; Lan, Y.; Lei, A. W. Angew. Chem., Int. Ed. 2014, 53, 502. (b) Zhou, Q. Q.; Guo, W.;
Ding, W.; Wu, X.; Chen, X.; Lu, L. Q.; Xiao, W. J. Angew. Chem., Int. Ed. 2015, 54, 11196. (c) Candish, L.; Freitag,
M.; Genscha, T.; Glorius, F. Chem. Sci. 2017, 8, 3618.
(11) (a) Bergonzini, G.; Cassani C.; Wallentin, C. J. Angew. Chem., Int. Ed. 2015, 54, 14066. (b) Pettersson, F. K.;
Bergonzini, G.; Cassani, C.; Wallentin, C. J. Chem. Eur. J. 2017, 23, 7444.
(12) Zhang, M.; Ruzi, R.; Xi, J.; Li, N.; Wu, Z.; Li, W.; Yu, S.; Zhu, C. Org. Lett. 2017, 19, 3430.
(13) Wang, Y.; Gulevich, A. V.; Gevorgyan, V. Chem. Eur. J. 2013, 19, 15836.
(14) Wertz, S.; Leifert, D.; Studer, A. Org. Lett. 2013, 15, 4.
12
ACS Paragon Plus Environment

Page 13 of 13
The Journal of Organic Chemistry
(15) Campo, M. A.; Larock, R. C. Org. Lett. 2000, 23, 3676.
1
2
3
4
5
6
7
(16) Lockner, J. W.; Dixon, D. D.; Risgaard , R.; Baran, P. S. Org. Lett. 2011, 13, 5628.
(17) Motiwala, H. F.; Vekariya, R. H.; Aube, J. Org. Lett. 2015, 17, 5484.
(18) Li, H.; Zhu, R.; Shi, W.; He, Ke.; Shi, Z. Org. Lett. 2012, 14, 4850.
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
ACS Paragon Plus Environment