Decarboxylative C-H arylation of benzoic acids under radical conditions

Article abstract of DOI:10.1021/ol3010694

A decarboxylative radical cyclization reaction has been developed for the synthesis of fluorenones. The reaction uses Ag(I)/K₂S ₂O₈ to oxidatively decarboxylate an aroylbenzoic acid to an aryl radical, which undergoes cyclization to afford fluorenone products in good yield.

Full text of DOI:10.1021/ol3010694

Decarboxylative C-H Arylation of Benzoic Acids under Radical Conditions
Sangwon Seo,† Mark Slater‡ and Michael F. Greaney†
*
†School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL,UK
‡Syngenta, Jealott's Hill International Research Centre, Bracknell, RG42 6EY, UK.
michael.greaney@manchester.ac.uk
Supporting Information
Contents
1: Experimental Procedures
2: NMR Spectra
S1
S12
I. Experimental Procedures
General Methods:
Melting points are uncorrected. Microwave experiments were performed in a Biotage microwave
initiator. The reactions were carried out in sealed pressure-proof vials with magnetic stirring. 1H and
13C NMR spectra were recorded on a Brüker Ava500 (500 MHz) instrument and calibrated to
residual solvent peaks: proton (CDCl3: 7.26 ppm, DMSO-d6: 2.50 ppm) and carbon (CDCl3: 77.0
1
ppm, DMSO-d6: 39.5 ppm). The H data is presented as follows: chemical shift (in ppm on the δ
scale), multiplicity (bs=broad singlet, s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet), the
13
coupling constant (J, in Hertz) and integration. The C data is reported as the ppm on the δ scale
followed by the interpretation. Electrospray and electron impact high resolution mass spectrometry
was performed using Thermo Finnigan MAT95XP mass spectrometer. The data is recorded as the
ionisation method followed by the calculated and measured masses. TLC was performed on Merck
60F254 silica plates and visualised by UV light and potassium permanganate stains. The compounds
were purified by flash chromatography using Merck Kieselgel 60 (particle size 40-63 μm) silica
under a positive pressure. The eluent is quoted as a percentage. Anhydrous tetrahydrofuran used for
starting material preparation and deuterated acetonitrile used for the coupling reaction were bought
from Sigma-Aldrich and used as received. All other chemicals were purchased from a chemical
supplier and used as received.
S1

Preparation of Starting Materials:
Scheme S1. Preparation of benzoylbenzoic acid starting materials.
Benzoic acids 1a, 1b, 1d, 1f, 1m, and 1n were purchased from commercial suppliers. All other
starting materials were prepared according to the literature procedure of Parham and Piccirilli
(Scheme S1).1 Aryllithium derivatives were prepared at -78 °C, or at -100 °C for those substrates
containing nitro substituents (1o and 1p).
Figure S1. Commercially available starting materials.
2-(4-Trifluoromethylbenzoyl)benzoic acid (1c)
White Solid (Recrystallised from CHCl3); Yield = 46%; Mp = 186 –
1
188 °C; H NMR (500 MHz, DMSO-d6 ): 13.63 (br s, 1 COOH), 8.03
(d, J = 7.4 Hz, 1H), 7.88 (d, J = 7.7 Hz, 2H), 7.81 (d, J = 7.8 Hz, 2H),
7.78 (td, J = 7.5, 1.2 Hz, 1H), 7.71 (td, J = 7.6, 1.2 Hz, 1H), 7.51 (d, J =
7.4 Hz, 1H); 13C NMR (125 MHz, DMSO-d6): 195.6 (CO), 166.8
(COOH), 140.4 (d, J = 70.5 Hz, quat), 132.8 (CH), 132.3 (d, J = 26.8 Hz, quat), 130.2 (CH), 129.9
(CH), 129.7 (quat), 129.4 (2CH), 127.5 (CH), 125.7 (q, J = 3.6 Hz, 2CH), 124.8 (quat), 122.7 (quat);
HRMS (ES+) cald. for (M+H)+ C15H10O3F3: 295.0577, found: 295.0577.
2-(4-Methoxybenzoyl)benzoic acid (1e)
White Solid (Recrystallised from MeCN); Yield = 52%; Mp = 148 –
1
150 °C; H NMR (500 MHz, DMSO-d6 ): 13.12 (br s, 1 COOH), 7.98
(dd, J = 7.8, 0.9 Hz, 1H), 7.70 (td, J = 7.5, 1.3 Hz, 1H), 7.63 (td, J=7.6,
1.3 Hz, 1H), 7.59 (d, J=8.8 Hz, 2H), 7.37 (dd, J=7.5, 0.9 Hz, 1H), 7.02 (d,
13
J=8.9 Hz, 2H), 3.82 (s, 3H); C NMR (125 MHz, DMSO-d6): 195.0
(CO), 166.9 (COOH), 163.1 (quat), 141.7 (quat), 132.3 (CH), 131.3 (2CH), 129.9 (quat), 129.8
(quat), 129.7 (CH), 129.5 (CH), 127.3 (CH), 113.9 (2CH), 55.5 (CH3); HRMS (ES+) cald. for
(M+H)+ C15H13O4: 257.0809, found: 257.0800.
S2

2-(4-Phenylbenzoyl)benzoic Acid (1g)
White Solid (Recrystallised from CHCl3); Yield = 57%; Mp = 230 –
231 °C; 1H NMR (500 MHz, DMSO-d6 ): 13.27 (br s, 1 COOH), 8.03
(d, J = 7.7 Hz, 1H), 7.79 (d, J = 8.3, 1.2 Hz, 2H), 7.76 – 7.66 (m, 6H),
7.49 (t, J = 7.5 Hz, 2H), 7.46 (d, J = 7.4 Hz, 1H), 7.42 (t, J = 7.3 Hz,
13
1H); C NMR (125 MHz, DMSO-d6): 196.0 (CO), 166.9 (COOH),
144.5 (quat), 141.4 (quat), 138.9 (quat), 135.7 (quat), 132.5 (CH), 129.8
(CH), 129.7 (CH), 129.6 (CH), 129.1 (CH), 128.4 (CH), 127.4 (CH), 127.0 (CH), 126.9 (CH);
HRMS (ES+) cald. for (M+H)+ C20H15O3: 303.1016, found: 303.1019.
2-(3,5-Dimethylbenzoyl)benzoic acid (1h)
White Solid (Recrystallised from CHCl3); Yield = 60%; Mp = 178 – 180 °C;
1H NMR (500 MHz, DMSO-d6 ): 13.16 (br s, 1 COOH), 7.98 (d, J = 7.5
Hz, 1H), 7.71 (td, J = 7.5, 1.2 Hz, 1H), 7.64 (td, J = 7.6, 1.3 Hz, 1H), 7.37 (d,
J = 7.2 Hz, 1H), 7.25 (s, 1H), 7.24 (s, 2H), 2.27 (s, 6H); 13C NMR (125 MHz,
DMSO-d6): 196.5 (CO), 166.9 (COOH), 141.6 (quat), 137.8 (quat), 137.0
(quat), 134.5 (CH), 132.3 (CH), 129.9 (quat), 129.7 (CH), 129.6 (CH), 127.4
(CH), 126.6 (CH), 20.7 (CH3); HRMS (ES+) cald. for (M+H)+ C16H15O3: 255.1016, found:
255.1018.
2-(2-Fluorobenzoyl)benzoic acid (1i)
White Solid (Recrystallised from CHCl3); Yield = 51%; Mp = 136 – 138 °C;
1H NMR (500 MHz, DMSO-d6 ): 13.27 (br s, 1 COOH), 7.94 (d, J = 7.6 Hz,
1H), 7.71 (t, J = 7.4 Hz, 1H), 7.66 – 7.62 (m, 3H), 7.43 (dd, J = 7.6, 0.9 Hz,
13
1H), 7.32 (td, J = 7.6, 0.9 Hz, 1H), 7.26 (t, J = 9.1 Hz, 1H); C NMR (125
MHz, DMSO-d6): 193.2 (CO), 167.1 (COOH), 160.9 (d, J = 256.2 Hz, quat),
143.0 (quat), 135.1 (d, J = 7.9 Hz, CH), 132.4 (CH), 131.0 (CH), 129.9 (CH), 129.6 (CH), 129.4
(quat), 126.9 (CH), 125.4 (d, J = 8.6 Hz, quat), 124.5 (d, J = 3.2 Hz, CH), 116.7 (d, J = 22.1 Hz,
CH); HRMS (ES+) cald. for (M+H)+ C14H10O3F: 245.0609, found: 245.0601.
2-(2-Methoxybenzoyl)benzoic acid (1j)
White Solid (Recrystallised from MeCN); Yield = 65%; Mp = 146 – 147 °C;
1H NMR (500 MHz, DMSO-d6 ): 13.00 (br s, 1 COOH), 7.85 (dd, J = 7.6,
0.9 Hz, 1H), 7.63 – 7.54 (m, 4H), 7.28 (dd, J = 7.6, 1.0 Hz, 1H), 7.09 (d, J =
8.0 Hz, 1H), 7.05 (t, J = 7.5 Hz, 1H), 3.50 (s, 3H); 13C NMR (125 MHz,
DMSO-d6): 195.0 (CO), 167.6 (COOH), 158.8 (quat), 144.1 (quat), 134.3
(CH), 131.6 (CH), 130.9 (CH), 130.0 (quat), 129.2 (CH), 129.0 (CH), 126.8 (CH), 126.5 (quat),
120.3 (CH), 112.9 (CH), 55.6 (CH3); HRMS (ES+) cald. for (M+H)+ C15H13O4: 257.0809, found:
257.0798.
2-(3-Chlorobenzoyl)benzoic acid (1k)
White Solid (Recrystallised from MeCN); Yield = 55%; Mp = 166 –
168 °C; 1H NMR (500 MHz, DMSO-d6 ): 13.33 (br s, 1 COOH), 8.01 (d,
J = 7.6 Hz, 1H), 7.75 (td, J = 7.5, 1.2 Hz, 1H), 7.73 – 7.69 (m, 1H), 7.68 (td,
13
J = 7.6, 1.3 Hz, 1H), 7.61 (s, 1H), 7.54 – 7.46 (m, 3H); C NMR (125
MHz, DMSO-d6): 195.2 (CO), 166.8 (COOH), 140.6 (quat), 138.8 (quat),
133.5 (quat), 132.8 (CH), 132.7 (CH), 130.8 (CH), 130.1 (CH), 129.8 (CH), 129.7 (quat), 127.8
(CH), 127.6 (CH), 127.4 (CH); HRMS (ES+) cald. for (M+H)+ C14H10O3Cl: 261.0313, found:
261.0313.
S3

2-(2-Nitrobenzoyl)benzoic acid (1o)
White Solid (Recrystallised from CHCl3); Yield = 37%; Mp = 174 – 176 °C;
1H NMR (500 MHz, DMSO-d6 ): 13.33 (br s, 1 COOH), 8.07 (d, J = 7.8 Hz,
1H), 7.86 – 7.81 (m, 2H), 7.78 (td, J = 7.4, 0.9 Hz, 1H), 7.71 (td, J = 7.5, 1.3
Hz, 1H), 7.67 (td, J = 7.4, 0.9 Hz, 1H), 7.51 (t, J = 7.2 Hz, 2H); 13C NMR (125
MHz, DMSO-d6): 193.2 (CO), 168.1 (COOH), 148.1 (quat), 137.5 (quat),
133.0 (CH), 132.9 (CH), 132.5 (quat), 132.1 (quat), 131.8 (CH), 131.4 (CH), 130.7 (CH), 129.3
(CH), 129.1 (CH), 124.3 (CH); HRMS (ES+) cald. for (M+H)+ C14H10NO5: 272.0554, found:
272.0553.
2-(2-Methyl-6-nitrobenzoyl)benzoic acid (1p)
White Solid (Recrystallised from CHCl3); Yield = 33%; Mp = 218 – 220 °C;
1H NMR (500 MHz, DMSO-d6 ): 13.23 (br s, 1 COOH), 8.12 (d, J = 7.9 Hz,
1H), 7.75 (d, J = 7.5 Hz, 1H), 7.71 (td, J = 7.4, 1.3 Hz, 1H), 7.70 (t, J = 7.9 Hz,
1H), 7.62 (dd, J = 7.6, 0.9 Hz, 1H), 7.54 (td, J = 7.5, 1.2 Hz, 1H), 7.49 (dd, J =
7.8, 1.0 Hz, 1H), 2.18 (s, 3H); 13C NMR (125 MHz, DMSO-d6): 193.3 (CO),
170.1 (COOH), 146.7 (quat), 137.4 (quat), 136.9 (CH), 135.2 (quat), 134.0 (quat), 133.6 (quat),
133.5 (CH), 130.6 (CH), 130.0 (CH), 128.1 (CH), 122.4 (CH), 18.7 (CH3); HRMS (ES+) cald. for
(M+H)+ C15H12NO5: 286.0710, found: 286.0711.
Optimisation of Decarboxylative Coupling
Initial Result:
Scheme S2. Initial result in Ag-catalysed intramolecular direct arylation of benzoic acids
After screening intramolecular direct arylation of various benzoic acids, we found that 2-
benzoylbenzoic acid 1a afforded the desired product 3a in 29% isolated yield when reacted in the
presence of 20 mol% of AgOAc and 3 equiv of K2S2O8 in MeCN at 100 °C. Under these conditions,
the decarboxylation was efficient, with the low yield of 3a being due to the formation of the
protodecarboxylation by-product 4a and its difficult separation from 3a using column
chromatography (Table S1).
S4

Screening of the Reaction Parameters
Yield 3aa
(%)
29
Ratio
3a:4ab
1:1.2
1:1.2
-
Entry
Oxidant
Solvent
T (°C)
1
2c
3
K2S2O8
K2S2O8
-
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN-d3
Solventi
EtCN
100
100
100
80
15
n.d.
<5d
31
6
n.d.
26
4
K2S2O8
K2S2O8
K2S2O8
Oxidantf
(NH4)2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
-
5
120
100
100
100
100
100
100
100
100
100
130
1:1.2
1:1.2
-
1:1.2
1:1.2
9:1h
-
1:3.3
1:3.6
9:1h
9:1h
6e
7
8
9g
10
11
12
13
14j
15j
27
69
<5d
14
iPrCN
MeCN-d3
MeCN-d3
8
45
76
aIsolated yields; n.d. = Not determined as no product was observed by LC/MS analysis.
c
bRatio determined by NMR integration. Reaction under anhydrous condition; 4Å M.S.,
d
e
anhydrous MeCN and under N2 (1 atm). Yields estimated by LC/MS. 10% AgOAc.
fOxidant: Ce(SO4)2 and PhI(OAc)2. 10 mol% Pd(OAc)2. By-product is deutero-
decarboxylated product 4a. Solvent: CHCl3, H2O, EtOH, TFE, 1-chlorobutane, DCE,
g
h
i
NMP, 1,2-Dimethoxyethane, DMF, Pyridine, THF, MeNO2, Xylene, Benzene,
Chlorobenzene, PhCF3, PhCF3/H2O (1:1), DMSO, DMA, Di(ethylene glycol), CCl4,
Toluene, Acetone, PhCN, NEt3, Cyclohexane, Vinyl acetate, Mesitylene, 1,4-Dioxane,
(CF3)2CHOH, TFA. jMicrowave heating for 1 hour.
Table S1. Intramolecular direct arylation of 2-benzoylbenzoic acid: 1a (0.3 mmol), AgOAc (0.06
mmol), oxidant (0.9 mmol) and solvent (2.0 mL) in a sealed microwave vial, 20 h, conventional
heating. A preliminary screen of silver salts showed little variation.
S5

Entry
1
solvent
d3-MeCN / H2Ob
d3-MeCN / H2O
d3-MeCN / H2O
H2O
temp (°C)
130c
100
yield 3a (%)a
23 – 35
2d
30
28
2
0
0
14
19
0
0
0
3d,e
4
100
130c
100
5d
H2O
H2O
H2O
H2O
H2O
H2O
H2O
6d,f
7d,e,f
8e,f,g
9h
100
100
100
100
100
100
100
100
10i
11j
12d,f
13d,f
14d,e,f
2M HCl (aq)
2M H2SO4 (aq)
2M H2SO4 (aq)
0
0
8
100
Conditions: 1a (0.3 mmol), AgOAc (20 mol%), K2S2O8 (3 equiv) and
solvent (2.0 mL) in a sealed microwave vial, 20 h, conventional
a
heating. Yield determined by NMR analysis using MeNO2 as an
b
internal standard Various ratios of the mixture of d3-MeCN / H2O
(1:2, 1:1, 9:1, 19:1 and 49:1) have been tried, all giving similar poor
yields with most starting material being recovered. A longer reaction
c
d
time does not improve the yield. Microwave heating. 1 ml of
saturated aqueous solution of K2S2O8 (~0.65 equiv) added into the
e
reaction mixture in 1 ml of solvent. Slow addition of sat. K2S2O8 (aq)
f
g
over ~10 h. AgNO3 instead of AgOAc. 3 mL of saturated aqueous
solution of K2S2O8 (~1.95 equiv) added into the reaction mixture in 1
mL of solvent. h 0.3 equiv K2S2O8. i 0.1 equiv K2S2O8. j No K2S2O8.
Table S2. Investigation into aqueous reaction conditions.
S6

Figure S2. LC/MS traces of reaction in MeCN
Figure S3. LC/MS traces of reaction in MeCN-d3
S7

Decarboxylative C-H coupling reaction:
Scheme S3. Decarboxylative coupling.
General procedure: A septum-sealed microwave tube (5 mL) charged with compound 1 (0.3
mmol), AgOAc (10.0 mg, 0.06 mmol) and K2S2O8 (243.3 mg, 0.9 mmol) in MeCN-d3 (2 mL) was
irradiated in a microwave reactor at 130 °C for 1 hour. The reaction mixture was allowed to cool
down, diluted with Et2O (10 mL) and poured into H2O (5 mL). The resulting mixture was extracted
repeatedly with 10 mL portions of Et2O. The combined organic layers were dried over MgSO4,
filtered, and concentrated under reduced pressure. The crude was purified by column
chromatography (SiO2, Et2O/Hexane: 5 – 40 %) to yield the product 3 as a yellow or pale yellow
solid.
Fluoren-9-one (3a)2
1
Yellow solid; Yield = 76% from 1a and 25% from 1o; H NMR (500 MHz,
CDCl3): 7.66 (d, J = 7.4 Hz, 2H), 7.52 – 7.47 (m, 4H), 7.30 (td, J = 7.2, 1.9 Hz,
2H); 13C NMR (125 MHz, CDCl3): 193.9 (CO), 144.3 (quat), 134.6 (CH), 134.0
(quat), 129.0 (CH), 124.2 (CH), 120.2 (CH).
3-Fluorofluoren-9-one (3b)2
Pale yellow Solid; Yield = 70%; 1H NMR (500 MHz, CDCl3): 7.67 – 7.65 (m,
2H), 7.53-7.49 (m, 2H), 7.34 (td, J = 6.9, 1.9 Hz, 1H), 7.20 (dd, J = 8.3, 2.2 Hz,
1H), 6.95 (td, J = 8.6, 2.2 Hz, 1H); 13C NMR (125 MHz, CDCl3): 192.1 (CO),
168.3 (quat), 166.3 (quat), 147.5 (d, J = 9.9 Hz, quat), 142.8 (quat), 134.7 (CH),
130.2 (d, J = 2.7 Hz, quat), 129.8 (CH), 126.5 (d, J = 10.1 Hz, CH), 124.3 (CH),
120.6 (CH), 115.5 (d, J = 23.2 Hz, CH), 108.4 (d, J = 24.4 Hz, CH).
3-(Trifluoromethyl)fluoren-9-one (3c)3
1
Pale Yellow Solid; Yield = 77%; H NMR (500 MHz, CDCl3): 7.76 (d, J =
7.8 Hz, 1H), 7.75 (s, 1H), 7.71 (d, J = 7.4 Hz, 1H), 7.60 – 7.54 (m, 3H), 7.37
13
(td, J = 7.4, 1.1 Hz, 1H); C NMR (125 MHz, CDCl3): 192.5 (CO), 144.9
(quat), 143.2 (quat), 136.6 (quat), 136.1 (q, J = 32.1 Hz, quat), 135.3 (CH),
133.9 (quat), 130.0 (CH), 126.3 (q, J = 4.0 Hz, CH), 124.8 (CH), 124.4 (CH),
123.5 (q, J = 272.9 Hz, quat), 120.8 (CH), 117.2 (q, J = 3.7 Hz, CH).
3-Chlorofluoren-9-one (3d)2
1
Pale Yellow Solid; Yield = 84%; H NMR (500 MHz, CDCl3): 7.68 (d, J =
7.3 Hz, 1H), 7.59 (d, J = 7.9 Hz, 1H), 7.52 – 7.50 (m, 3H), 7.37 – 7.32 (m, 1H),
13
7.27 (dd, J = 7.9, 1.7 Hz, 1H); C NMR (125 MHz, CDCl3): 192.5 (CO),
146.1 (quat), 143.1 (quat), 141.0 (quat), 134.9 (CH), 134.4 (quat), 132.4 (quat),
129.8 (CH), 129.0 (CH), 125.4 (CH), 124.6 (CH), 121.0 (CH), 120.6 (CH).
S8

3-Methoxyfluoren-9-one (3e)3
1
Yellow Solid; Yield = 58%; H NMR (500 MHz, CDCl3): 7.63 (d, J = 7.3
Hz, 1H), 7.62 (d, J = 8.2 Hz, 1H), 7.49 – 7.45 (m, 2H), 7.30 (td, J = 7.0, 1.8
Hz, 1H), 7.02 (d, J = 2.2 Hz, 1H), 6.74 (dd, J = 8.2, 2.2 Hz, 1H), 3.91 (s, 3H);
13C NMR (125 MHz, CDCl3): 192.5 (CO), 165.4 (quat), 147.0 (quat), 143.3
(quat), 135.4 (quat), 134.1 (CH), 129.3 (CH), 127.2(quat), 126.3 (CH), 123.9
(CH), 120.1 (CH), 113.0(CH), 107.1 (CH), 55.8 (CH3).
3-Methylfluoren-9-one (3f)2
Yellow Solid; Yield = 46%; 1H NMR (500 MHz, CDCl3): 7.63 (d, J = 7.2 Hz,
1H), 7.54 (d, J = 7.5 Hz, 1H), 7.49 – 7.44 (m, 2H), 7..32 (s, 1H), 7.27 (td, J = 7.1,
1.6 Hz, 1H), 7.08 (d, J = 7.1 Hz, 1H), 2.42 (s, 3H); 13C NMR (125 MHz, CDCl3):
193.6 (CO), 145.8 (quat), 144.8 (quat), 144.3 (quat), 134.7 (quat), 134.4 (CH),
131.8 (quat), 129.6 (CH), 128.9 (CH), 124.3 (CH), 124.1 (CH), 121.2 (CH),
120.0 (CH), 22.2 (CH3).
3-Phenylfluoren-9-one (3g)2
1
Yellow solid; Yield = 65%; Mp = 230 – 231 °C; H NMR (500 MHz,
CDCl3): 7.72 – 7.71 (m, 2H), 7.68 – 7.64 (m, 3H), 7.57 (d, J = 7.4 Hz, 1H),
7.52 – 7.48 (m, 4H), 7.44 – 7.41 (m, 1H), 7.32 (td, J = 7.4, 0.9 Hz, 1H); 13C
NMR (125 MHz, CDCl3): 193.5 (CO),147.8 (quat), 145.1 (quat), 144.1
(quat), 140.2 (quat), 134.7 (quat), 134.6 (CH), 132.9 (quat), 129.2 (CH),
128.9 (2CH), 128.4 (CH), 127.9 (CH), 127.2 (2CH), 124.7 (CH), 124.2
(CH), 120.3 (CH), 119.2 (CH); HRMS (ES+) cald. for (M+H)+ C19H13O:
257.0961, found: 257.0952.
2,4-Dimethylfluoren-9-one (3h)3
Yellow solid; Yield = 45%; 1H NMR (500 MHz, CDCl3): 7.64 (d, J = 7.2 Hz,
1H), 7.55 (d, J = 7.5 Hz, 1H), 7.45 (td, J = 7.5, 1.2 Hz, 1H), 7.33 (s, 1H), 7.24
(td, J = 7.4, 0.7 Hz, 1H), 7.05 (s, 1H), 2.53 (s, 3H), 2.33 (s, 3H); 13C NMR (125
MHz, CDCl3): 194.5 (CO), 145.5 (quat), 139.5 (quat), 138.9 (quat), 137.9
(CH), 134.8 (quat), 134.6 (CH), 134.5 (quat), 133.3 (quat), 127.9 (CH), 124.1
(CH), 122.9 (CH), 122.6 (CH), 21.1 (CH3), 20.0 (CH3).
1-Fluorofluoren-9-one (3i)2
1
Pale Yellow Solid; Yield = 69%; H NMR (500 MHz, CDCl3): 7.68 (d, J = 7.4
Hz, 1H), 7.54 (d, J = 7.2 Hz, 1H), 7.51 (td, J = 7.3, 1.0 Hz, 1H), 7.50 – 7.46 (m,
1H), 7.35 – 7.32 (m, 2H), 6.95 (t, J = 8.6 Hz, 1H); 13C NMR (125 MHz, CDCl3):
190.2 (CO), 160.3 (quat), 158.3 (quat), 146.3 (d, J = 3.6 Hz, quat), 143.4 (d, J =
3.5 Hz, quat), 137.0 (d, J = 8.3 Hz, CH), 134.6 (CH), 133.9 (quat), 129.7 (CH),
124.5 (CH), 120.6 (CH), 117.5 (d, J = 20.9 Hz, CH), 116.4 (d, J = 2.9 Hz, CH).
1-Methoxyfluoren-9-one (3j)4
Yellow Solid; Yield = 51%; 1H NMR (500 MHz, CDCl3): 7.65 (d, J = 7.4 Hz,
1H), 7.50 (d, J = 7.4 Hz, 1H), 7.45 (t, J = 7.9 Hz, 2H), 7.29 (t, J = 7.4 Hz, 1H),
13
7.14 (d, J = 7.3 Hz, 1H), 6.84 (d, J = 8.5 Hz, 1H), 3.99 (s, 3H); C NMR (125
MHz, CDCl3): 191.9 (CO), 158.4 (quat), 146.5 (quat), 143.2 (quat), 136.8
(CH), 134.5 (quat), 133.9 (CH), 129.2 (CH), 123.9 (CH), 120.2 (CH), 120.1
(quat), 113.0 (CH), 112.9 (CH), 55.9 (CH3).
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2-Chlorofluoren-9-one (3k) and 4-Chlorofluoren-9-one (3l)5
Isolated as an inseparable mixture of regioisomers (3k:3l
= 1:1.4); Pale yellow solid; Yield = 70 %; 2-
1
Chlorofluoren-9-one (2k): H NMR (500 MHz, CDCl3):
7.66 (d, J = 7.4 Hz, 1H), 7.61 (s, 1H), 7.50 (d, J = 3.9
13
Hz, 2H), 7.45 – 7.44 (m, 2H), 7.33 – 7.29 (m, 1H); C
NMR (125 MHz, CDCl3): 192.4 (CO), 143.6 (quat),
142.5 (quat), 135.6 (quat), 135.0 (CH), 134.9 (CH), 134.0 (quat), 133.9 (quat), 129.3 (CH), 124.6
1
(CH), 124.5 (CH), 121.3 (CH), 120.4 (CH); 4-Chlorofluoren-9-one (2l)5: H NMR (500 MHz,
CDCl3): 8.17 (d, J = 7.6 Hz, 1H), 7.70 (d, J = 7.2 Hz, 1H), 7.59 (d, J = 7.2 Hz, 1H), 7.54 (t, J = 7.6
Hz, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 7.4 Hz, 1H), 7.24 (t, J = 7.6 Hz, 1H); 13C NMR (125
MHz, CDCl3): 192.5 (CO), 143.1 (quat), 140.6 (quat), 136.3 (quat), 136.1 (CH), 135.0 (quat),
134.1 (CH), 130.0 (CH), 129.5 (quat), 129.4 (CH), 124.4 (CH), 124.1 (CH), 122.5 (CH).
3-Chloro-4-nitrofluoren-9-one (3m)
The major regioisomer was isolated as pale yellow solid; Yield = 56%; Mp =
198 – 200 °C; 1H NMR (500 MHz, CDCl3): 7.76 (d, J = 7.2 Hz, 1H), 7.73 (d,
J = 7.9 Hz, 1H), 7.55 (td, J = 7.6, 1.2 Hz, 1H), 7.47 (d, J = 7.9 Hz, 1H), 7.45 (td,
J = 7.6 Hz, 1H), 7.38 (d, J = 7.2 Hz, 1H); 13C NMR (125 MHz, CDCl3): 189.7
(CO), 138.6 (quat), 136.3 (quat), 135.6 (CH), 134.0 (quat), 133.9 (quat), 131.3
(CH), 131.0 (quat), 130.9 (CH), 126.1 (CH), 125.2 (CH), 122.5 (CH); HRMS
(ES+) cald. for (M+H)+ C13H7NO3Cl: 260.0109, found: 260.0108.
8-Methoxybenzo[a]fluoren-11-one (3n)6
Prepared as with general procedure but an additional equivalent of AgOAc
(10.0 mg, 0.06 mmol) and K2S2O8 (243.3 mg, 0.9 mmol) were added and
further heated for 1 h under microwave irradiation. Yellow solid; Yield =
1
31%; H NMR (500 MHz, CDCl3): 8.96 (dd, J = 8.5, 0.7 Hz, 1H), 7.96
(d, J = 8.2 Hz, 1H), 7.77 (d, J = 8.3 Hz, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.58
– 7.55 (m, 1H), 7.55 (d, J = 8.1 Hz, 1H), 7.43 (m, 1H), 7.00 (d, J = 2.2 Hz, 1H), 6.68 (dd, J = 8.1,
13
2.2 Hz, 1H), 3.90 (s, 3H); C NMR (125 MHz, CDCl3): 194.2 (CO), 165.0 (quat), 146.3 (quat),
144.6 (quat), 135.2 (CH), 134.5 (quat), 130.0 (quat), 129.2 (CH), 128.4 (CH), 128.1 (quat), 127.4
(quat), 126.4 (CH), 125.7 (CH), 124.3 (CH), 117.9 (CH), 111.9 (CH), 107.7 (CH), 55.7 (CH3).
2-Nitrofluoren-9-one (3o)7
1
Yellow solid; Yield = 12%; H NMR (500 MHz, CDCl3): 7.76 (dd, J = 7.5,
0.7 Hz, 1H), 7.73 (d, J = 7.4 Hz, 1H), 7.64 (t, J = 7.7 Hz, 1H), 7.61 – 7.55 (m,
3H), 7.40 (td, J = 7.3, 1.2 Hz, 1H); 13C NMR (125 MHz, CDCl3): 187.5 (CO),
146.6 (quat), 146.3 (quat), 142.1 (quat), 135.5 (CH), 135.3 (CH), 133.3 (quat),
130.5 (CH), 125.3 (CH), 125.0 (quat), 123.6 (CH), 123.1 (CH), 120.7 (CH).
1-Methylfluoren-9-one (3p)3
Following the general procedure, decarboxylation/denitration product 3p was
obtained from 2-(2-Methyl-6-nitrobenzoyl)benzoic acid 1p. Yellow solid; Yield =
27%; 1H NMR (500 MHz, CDCl3): 7.62 (d, J = 7.3 Hz, 1H), 7.50 (d, J = 7.3 Hz,
1H), 7.46 (td, J = 7.3, 1.1 Hz, 1H), 7.36 – 7.32 (m, 2H), 7.28 (td, J = 7.3, 1.2 Hz,
1H), 7.04 (d, J = 7.0 Hz, 1H), 2.63 (s, 3H); 13C NMR (125 MHz, CDCl3): 195.1
(CO), 144.8 (quat), 143.8 (quat), 139.5 (quat), 134.3 (CH), 134.0 (CH), 131.8 (CH), 130.9 (quat),
128.9 (CH), 123.8 (CH), 120.0 (CH), 117.8 (CH), 17.8 (CH3).
S10

References
1.
Parham, W. E.; Piccirilli, R. M., J. Org. Chem. 1976, 41, 1268-1269.
2.
Thirunavukkarasu, V. S.; Parthasarathy, K.; Cheng, C.-H., Angew. Chem. Int. Ed. 2008, 47, 9462-
9465.
3.
Liu, T.-P.; Liao, Y.-X.; Xing, C.-H.; Hu, Q.-S., Org. Lett. 2011, 13, 2452-2455.
4.
Zhao, Y.-B.; Mariampillai, B.; Candito, D. A.; Laleu, B.; Li, M.; Lautens, M., Angew. Chem. Int. Ed.
2009, 48 (10), 1849-1852.
5.
6.
Zhao, J.; Yue, D.; Campo, M. A.; Larock, R. C., J. Am. Chem. Soc. 2007, 129, 5288-5295.
Martins, C. I.; Coelho, P. J.; Carvalho, L. M.; Oliveira-Campos, A. M. F.; Samat, A.; Guglielmetti,
R., Helv. Chim. Acta 2003, 86, 570-578.
7. Zeng, W.; Ballard, T. E.; Tkachenko, A. G.; Burns, V. A.; Feldheim, D. L.; Melander, C., Bioorg.
Med. Chem. Lett. 2006, 16, 5148-5151.
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