CC BY-ND-NC 4.0 · SynOpen 2018; 02(04): 0268-0275
DOI: 10.1055/s-0037-1610663
paper
Copyright with the author

Palladium-Catalysed Coupling and Acid-Mediated Cyclisation: Synthesis of Fluorenones and Fluorenes

,
Dakoju Ravi Kishore
,
Gedu Satyanarayana*
Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi – 502 285, Sangareddy, Telangana, India   Email: gvsatya@iith.ac.in
› Author Affiliations
We are grateful to the Department of Science and Technology-Science and Engineering Research Board (DST-SERB) [NO.:SB/S1/OC-39/2014], New Delhi, for the financial support. D. R. K. and D. R. K. thank UGC, New Delhi, for the award of Research Fellowships.
Further Information

Publication History

Received: 18 July 2018

Accepted after revision: 16 September 2018

Publication Date:
30 October 2018 (online)

 

Abstract

Palladium-catalysed sequential one-pot synthesis of fluorenones is described. The reaction comprises intermolecular Suzuki coupling and intramolecular acid-mediated cyclisation in a one-pot procedure. The protocol is also applied to the synthesis of fluorenes using a single column purification.


#

One-pot or sequential one-pot strategies enhance synthetic efficiency and enable access to diversified molecules.[1] Fluorenones comprise fused tricyclic frameworks of biological and pharmaceutical significance,[2] through scavenging of redundant radicals in the body.[3] Significantly, the fluorenone core constitutes a complete carbon skeleton in certain natural products.[3] [4] As a result of interest in developing new synthetic strategies for the preparation of fluorenones, some interesting approaches have been established.[5] Conventional synthetic paths for the preparation of fluorenones involve Friedel–Crafts ring closure of biarylcarboxylic acids and the oxidation of fluorenes,[6] which usually involves several synthetic steps. Other methods for the synthesis of fluorenones include radical cyclisation,[7] transition-metal catalysed ring closure of benzophenones and biphenyl-2-carbonitrile,[8] and cyclocarbonylation of 2-halobiaryls.[9] In particular, Hilt and co-workers have synthesised fluorenones by using an intramolecular Friedel–Crafts acylation of biphenyl 2-carboxylic acid esters.[10]

Functionalised fluorenes are useful materials for optical brightening agents, dyes and ligands in organometallic chemistry.[11] Similar to fluorenones, conventional approaches for the synthesis of fluorenes are also mostly based on multistep approaches. For example, Jana et al. prepared fluorenes from 2-phenylbenzyl alcohols by using a Lewis acid mediated Friedel–Crafts reaction as the key reaction.[12] Wang et al. accomplished the synthesis of fluorenes from N-tosylhydrazones by a carbene aromatic substitution reaction.[13] The research group of Sarkar has described the preparation of fluorenes from ortho-bromobenzaldehydes in a two-step process.[14]

Although the established methodologies that are used to synthesise fluorenones are effective, they are stepwise and require advanced synthetic precursors. Therefore, there is scope for the development new protocols, particularly one-pot versions. To our knowledge, there are no reports on the synthesis of fluorenones using a one-pot process and simple starting materials. Based on our interest in the development of one-pot or sequential one-pot processes,[15] we have recently presented a synthesis of fluorenones from benzylamines and iodoarenes, under palladium-catalysed functional group-directing triple ortho-C–H activation.[16a] More recently, we described the synthesis of fluorenones via Suzuki coupling and subsequent oxidative cyclisation in a sequential one-pot manner.[16b] Herein, we present a one-pot approach to the synthesis of fluorenones through palladium-catalysed coupling of ortho-bromobenzoic acid esters and arylboronic acids and subsequent intramolecular Friedel­–Crafts acylation. Furthermore, the strategy was applied to the synthesis of fluorenes by using the same strategy, with a single column purification.

To begin with, it was anticipated that fluorenone 4aa could be obtained in a sequential one-pot operation by employing an intramolecular Friedel–Crafts acylation of the Suzuki product biphenyl ester 3aa generated in situ (Table [1]). Based on our earlier achievements in the synthesis of indanones[17] and dihydrocoumarins,[18] it was conceived that Friedel–Crafts acylation in situ of relatively inert biphenyl ester 3aa could only be feasible in the presence of a sufficiently­ strong acid. Furthermore, to promote in situ acylation­ in a one-pot protocol, some acid will be sacrificed to quench the base used for the initial Suzuki coupling step.

Thus, the screening study was initiated with 2-bromoethyl benzoate 1a and phenylboronic acid 2a. Suzuki coupling was performed in the presence of Pd(OAc)2 (5 mol%) and K2CO3 (2 equiv) in various solvents, at 80 °C for 15 to 24 h (Table [1], entries 1–15). After confirming the formation of Suzuki product 3aa, by TLC, the subsequent Friedel–Crafts acylation to give the desired fluorenone 4aa was carried out by the addition of different acids to the reaction mixture at room temperature and the resultant reaction mixture was again heated (80 °C or 100 °C). Thus, treatment with conc. sulfuric acid at 100 °C for 5 h, gave fluorenone 4aa in trace amounts (entry 1) and TfOH at 100 °C gave a similar result (entry 2). A slight improvement was observed when conc. sulfuric acid was added to the Suzuki product in N,N-dimethylformamide (DMF) (entries 3 and 4); whereas fluorenone 4aa was obtained in moderate yield when 3aa in DMF was reacted with TfOH (entry 5). The reaction was inferior when TfOH was added to 3aa in a 1:1 mixture of DMF and H2O (entry 6) and there was no reaction with TfOH in CH3CN or DMSO (entries 7 and 8). Since most of such acid mediated reactions have been carried out in halogenated solvents, we decided to carry out both reactions in 1,2-dichloroethane (DCE).[19] Therefore, to the biaryl Suzuki product 3aa formed in DCE, TfOH was added and the mixture was heated at 80 °C, giving the desired product fluorenone 4aa in 58% yield (entry 9). Acylation with conc. sulfuric acid in DCE gave 4aa in 54% yield (entry 10). On the other hand, acylation with the addition of TfOH in CH2Cl2 furnished 4aa in moderate yield (entry 11). Gratifyingly, treatment of 3aa in DCE with 10 equiv of TfOH raised the yield to 68% (entry 12). On the contrary, when the amount of TfOH was further increased to 15 equiv, the yield of 4aa decreased to 40% (entry 13). Finally, reaction in DCE, with BF3·OEt2 or AlCl3 furnished 4aa in inferior yields (entries 14 and 15).

Table 1 Optimisation Study for the Formation of Fluorenone 4aa a

Entry

Solvent (2 mL)

Acidb

Temp (°C)

Time (h)

Yield 4aa (%)c

1

H2O

H2SO4

100

5

traced

2

H2O

TfOH

100

5

traced

3

DMF

H2SO4

100

5

20

4

DMF

H2SO4

100

10

23

5

DMF

TfOH

100

10

40

6

DMF + H2O (1:1)

TfOH

100

10

traced

7

CH3CN

TfOH

100

10

traced

8

DMSO

TfOH

100

10

traced

9

DCE

TfOH

80

10

58

10

DCE

H2SO4

80

10

54

11

CH2Cl2

TfOH

100

10

43

12

DCE

TfOH

80

10

68 e

13

DCE

TfOH

80

10

40f

14

DCE

BF3·OEt2

80

10

traced

15

DCE

AlCl3

80

10

traced

a Unless otherwise mentioned, all the reactions were carried out using 2-bromoethyl benzoate 1a (0.50 mmol), phenylboronic acid 2a (0.55 mmol), K2CO3 (1.0 mmol), acid (5 mmol), Pd(OAc)2 (5 mol%), TBAI (16 mg, 10 mol%) in a screw-cap vial.

b Acid (5 equiv) was used.

c Isolated yields of chromatographically pure products.

d Only a trace amount of product was formed.

e TfOH (10 equiv) was used.

f TfOH (15 equiv) has been used.

With the above optimized conditions established for the formation of 4aa (Table [1], entry 12), the one-pot process was examined with other 2-bromobenzoic acid esters 1ae and phenylboronic acids 2ag. Gratifyingly, the process proved to be generally applicable and delivered fluorenones 4aaff (Scheme [1]). In addition to ethyl 2-bromobenzoate, the protocol occurred smoothly with ortho-bromobenzoic acid esters bearing Me (1b), OMe (1c and 1d) and even electron deactivating F (1e) on the aromatic ring (Scheme [1]). The reaction was also compatible with different arylboronic acids 2ag. Thus, the strategy was successful with para-methyl and para-ethylphenylboronic acids 2d and 2e (4ae, 4be, 4cd, 4ce, 4dd, 4de and 4ed, Scheme [1]) and with electron-rich arylboronic acids such as 2f and 2g (4af, 4bg, 4cf, 4cg, 4df and 4ef, Scheme [1]). Significantly, the protocol was also successful with an arylboronic acid (2c) bearing an electron-deactivating functional group (4dc, Scheme [1]). Thus, this strategy shows a good substrate scope and furnishes a variety of fluorenones.

Zoom Image
Scheme 1 Synthesis of fluorenones 4aaef from 1ae and 2ag. Reaction conditions: 2-bromoethyl benzoate 1ae (0.5 mmol), arylboronic acid 2ag (0.55 mmol), Pd(OAc)2 (6 mg, 5 mol%), K2CO3 (138 mg, 1.0 mmol), TBAI (16 mg, 10 mol%), DCE (2 mL), 100 °C, 15 h. After confirming formation of the Suzuki product, TfOH (10 equiv) was added at 0 °C and the mixture was stirred at room temperature. Yields in parentheses are isolated yields of chromatographically pure products.

After the successful synthesis of fluorenones, we turned our attention to the synthesis of fluorenes. For this purpose, it was conceived that biaryl secondary alcohols would serve as ideal precursors for fluorenes. Based on our previous sequential one-pot protocols of palladium-catalysed Heck reaction and subsequent reduction of the carbonyl group,[20] a sequential one-pot Suzuki coupling and reduction sequence in a one-pot strategy was considered. Thus, intramolecular Friedel–Crafts alkylation reaction of biaryl secondary alcohols would generate the desired fluorenes. Since a polar solvent is required for smooth reduction of the carbonyl group of the Suzuki product, in this case the reaction between ortho-bromoacetophenone 5a and para-tolylboronic acid 2a was conducted in DNF in the presence of Pd(OAc)2 (5 mol%) and K2CO3 (2 equiv) at 80 °C for 24 h. After confirming formation of the Suzuki product 6aa, by TLC, the cooled reaction mixture was then subjected to reduction with NaBH4 in situ, at 0 °C to r.t., for 30 min. After work-up, the crude biaryl secondary alcohol 7aa was then treated with mild Lewis acid BF3·OEt2 in DCE, 0 °C to r.t., and fluorene 8aa was isolated in 77% overall yield after column chromatography (Scheme [2]). With these established conditions, the procedure was extended to the synthesis of a range of fluorenes derived from ortho-bromoacetophenones 5af and arylboronic acids 2ag, furnishing fluorenes 8adeg (Scheme [2]).

Zoom Image
Scheme 2 Synthesis of fluorenes 8adeg from 2ag and 5af. Reaction conditions: (i) Pd(OAc)2, TBAI, K2CO3, DMF, 80 °C, 24 h; (ii) NaBH4, 0 °C to r.t., 0.5 h; (iii) BF3·OEt2, DCE (2 mL), 0 °C to r.t. Reactions were performed with 2-bromo ketones 5ae (0.5 mmol), arylboronic acid 2ag (0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol %), K2CO3 (138 mg, 1.0 mmol), TBAI (16 mg, 10 mol %), DCE (2 mL), 100 °C, 15 h, after confirming formation of the Suzuki product, NaBH4 (37.8 mg, 1.0 mmol) was added at 0 °C then the reaction mixture was stirred at room temperature for 0.5 h. After confirming formation of the corresponding alcohol, BF3·OEt2 was added to the worked up reaction mixture. Yields in the parentheses are isolated yields of chromatographically pure products.

In conclusion, we have established a sequential one-pot strategy for the synthesis of fluorenones. Palladium-catalysed Suzuki coupling and acid-mediated intramolecular Friedel–Crafts acylation were employed in the one-pot protocol. In addition, Suzuki coupling, followed by reduction and intramolecular Friedel–Crafts alkylation in a one-pot protocol has been developed for the synthesis of fluorenes.

IR spectra were recorded with a Bruker Tensor 37 (FTIR) spectrophotometer. 1H NMR spectra were recorded with a Bruker Avance 400 (400 MHz) spectrometer in CDCl3; chemical shifts (δ, ppm) and coupling constants (Hz) are reported with reference to either internal standard tetramethylsilane (TMS) (δH =0.00 ppm) or CHCl3H = 7.25 ppm). 13C NMR spectra were recorded with a Bruker Avance 400 (100 MHz) spectrometer in CDCl3; chemical shifts (δ, ppm) are reported relative to CHCl3C = 77.00 ppm (central line of triplet)]. In the 13C NMR spectra, the nature of carbons (C, CH, CH2 and CH3) was determined by recording the DEPT-135 spectra, and given in parentheses as s = singlet (for C), d = doublet (for CH), t = triplet (for CH2) and q = quartet (for CH3). In the 1H NMR spectra, the following abbreviations are used throughout: s = singlet, d = doublet, t = triplet, q = quartet, qui = quin, sept = sept, dd = doublet of doublets, m = multiplet and br. s = broad singlet. The assignment of signals was confirmed by 1H, 13C carbon-proton decoupling and DEPT spectroscopy. High-resolution mass spectra (HRMS) were recorded with an Agilent 6538 UHD Q-TOF under electrospray ionisation (ESI) mode and atmospheric pressure chemical ionisation (APCI) mode. All small-scale anhydrous reactions were carried out using Schlenk tubes under an inert atmosphere. Reactions were monitored by TLC on silica gel using a combination of hexane and EtOAc as eluent. Reactions were generally run under argon or nitrogen atmosphere. Solvents were distilled prior to use; petroleum ether with a boiling range of 60 to 80 °C was used. Palladium acetate, potassium carbonate, TBAI, TfOH, NaBH4 and BF3·OEt2 were purchased from Sigma–Aldrich and used as received. 2-Bromoethyl benzoates were used as received. 2-Bromoaryl ketones were prepared from 2-bromobenzaldehydes by using standard Grignard and oxidation protocol. Acme silica gel (60–120 mesh) was used for column chromatography (ca. 20 g per gram of crude material).[15]


#

Synthesis of Fluorenones 4; General Procedure

In an oven-dried Schlenk tube, were added ethyl 2-bromobenzoate 1 (114–145 mg, 0.5 mmol), phenylboronic acid 2 (122–182 mg, 0.55 mmol), palladium acetate (5.6 mg, 5 mol%), potassium carbonate (138 mg, 1.0 mmol) and TBAI (16 mg, 10 mol%) followed by DCE (2.0 mL) at r.t. and the reaction mixture was stirred at 80 °C for 15 h. Progress of the reaction for the formation of Suzuki product was monitored by TLC until completion of reaction. The mixture was then cooled to r.t., TfOH (375 mg, 10 mmol) was added and the mixture was stirred at 80 °C for 10 h. Progress of the reaction for the formation of fluorenone 4 was monitored by TLC. On completion, the reaction was quenched with aq. NaHCO3 then diluted with aq. NH4Cl solution and extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with saturated NaCl solution, dried (Na2SO4), and filtered. Evaporation of the solvent under reduced pressure and purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc) furnished the fluorenone 4 (56 to 88%), as semi-solid/solid products. Some of the fluorenones have been reported in the literature.[5] [6] [16] [21]


#

Synthesis of Fluorenes 8; General Procedure

In an oven-dried Schlenk tube, were added 2-bromophenylketone 5 (100–137 mg, 0.5 mmol), phenylboronic acid 2 (122–182 mg, 0.55 mmol), palladium acetate (5.6 mg, 5 mol%) and potassium carbonate (138 mg, 1.0 mmol), followed by DMF (2.0 mL) at r.t. and the reaction mixture was stirred at 80 °C for 20 h. Progress of formation of the Suzuki product was monitored by TLC, then the mixture was cooled to r.t. To the reaction mixture was added NaBH4 (76 mg, 2 mmol) at 0 °C and stirring was continued at r.t. for 0.5 h and formation of alcohol 7 was monitored by TLC. After work-up, to the crude reaction mixture were added DCE (2 mL) and BF3·OEt2 (710 mg, 5 mmol) at ice temperature and the mixture was stirred at the same temperature for 1 h. Progress of the reaction for the formation of fluorene 8 was monitored by TLC. The reaction mixture was quenched with aq. NaHCO3 then diluted with aq. NH4Cl and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with saturated aq. NaCl, dried (Na2SO4), and filtered. Evaporation of the solvent under reduced pressure and purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc) furnished fluorenes 8 (67 to 88%), as semi-solid/solid products. Several of the fluorenes are already reported in the literature.[5] [6] [14] [21]


#

2-Ethyl-7-methyl-9H-fluoren-9-one (4be)

In an oven-dried Schlenk tube, were added 2-ethyl 2-bromobenzoate 1b (121.5 mg, 0.5 mmol), arylboronic acid 2e (83 mg, 0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol%), K2CO3 (138 mg, 1.0 mmol) and TBAI (16 mg, 10 mol%) followed by DCE (2.0 mL) at r.t. and the reaction mixture was stirred at 80 °C for 20 h. To the cooled reaction mixture at r.t., was added TfOH (755 mg, 5.0 mmol) and stirring was continued at 80 °C for 15 h. Purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc, 99:1 to 95:5) furnished 4be.

Yield: 84.4 mg (76%); yellow solid; TLC (petroleum ether/EtOAc 95:05; UV detection): Rf = 0.8 (1b), 0.6 (4be).

1H NMR (CDCl3, 400 MHz): δ = 7.46 (d, J = 0.9 Hz, 1 H, Ar-H), 7.42 (s, 1 H, Ar-H), 7.34 (d, J = 7.3 Hz, 1 H, Ar-H), 7.32 (d, J = 7.2 Hz, 1 H, Ar-H), 7.29–7.18 (m, 2 H, Ar-H), 2.64 (q, 2 H, J = 7.7 Hz, CH 2CH3), 2.34 (s, 3 H, Ar-CH3), 1.23 (t, 3 H, J = 7.7 Hz, CH2CH 3).

13C NMR (CDCl3, 100 MHz): δ = 194.5 (s, C=O), 145.2 (s, Ar-C), 142.3 (s, Ar-C), 142.0 (s, Ar-C), 138.7 (s, Ar-C), 135.0 (d, Ar-CH), 134.6 (s, Ar-C), 134.0 (s, Ar-C), 134.0 (d, Ar-CH), 124.9 (d, Ar-CH), 123.7 (d, Ar-CH), 119.9 (d, Ar-CH), 119.8 (d, Ar-CH), 28.7 (t, CH2), 21.3 (q, ArCH3), 15.3 (q, CH3).

HRMS (APCI+): m/z [M + H]+ calcd for [C16H15O]+: 223.1117; found: 223.1113.


#

2-Methoxy-7-methyl-9H-fluoren-9-one (4cd)

In an oven-dried Schlenk tube, were added ethyl 2-bromobenzoate 1c (129.5 mg, 0.5 mmol), arylboronic acid 2d (75 mg, 0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol%), K2CO3 (138 mg, 1.0 mmol) and TBAI (16 mg, 10 mol%) followed by DCE (2.0 mL) at r.t. and the reaction mixture was stirred at 80 °C for 20 h. To the cooled reaction mixture at r.t., was added TfOH (755 mg, 5.0 mmol) and stirring was continued at 80 °C for 15 h. Purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc, 99:1 to 95:5) furnished 4cd.

Yield: 78.5.0 mg (70%); yellow solid; TLC (petroleum ether/EtOAc 95:05; UV detection): Rf = 0.6 (1c), 0.3 (4cd).

1H NMR (CDCl3, 400 MHz): δ = 7.39 (s, 1 H, Ar-H), 7.32 (d, J = 8.2 Hz, 1 H, Ar-H), 7.25 (d, J = 7.4 Hz, 1 H, Ar-H), 7.20 (d, J = 8.2 Hz, 1 H, Ar-H), 7.16 (d, J = 2.4 Hz, 1 H, ArH), 6.94 (dd, J = 8.2, 2.4 Hz, 1 H, Ar-H), 3.83 (s, 3 H, ArOCH3), 2.33 (s, 3 H, ArCH3).

13C NMR (CDCl3, 100 MHz): δ = 194.1 (s, C=O), 160.5 (s, Ar-C), 142.2 (s, Ar-C), 137.9 (s, Ar-C), 137.2 (s, Ar-C), 136.0 (s, Ar-C), 135.2 (d, Ar-CH), 134.6 (s, Ar-C), 125.1 (d, Ar-CH), 121.0 (d, Ar-CH), 120.1 (d, Ar-CH), 119.4 (d, Ar-CH), 109.4 (d, Ar-CH), 55.7 (q, ArOCH3), 55.5 (q, ArOCH3), 21.2 (q, ArCH3).

HRMS (APCI+): m/z [M + H]+ calcd for [C15H13O2]+: 225.0910; found: 225.0890.


#

7-Ethyl-2,3-dimethoxy-9H-fluoren-9-one (4de)

In an oven-dried Schlenk tube, were added ethyl 2-bromobenzoate 1d (144.5 mg, 0.5 mmol), arylboronic acid 2e (83 mg, 0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol%), K2CO3 (138 mg, 1.0 mmol), and TBAI (16 mg, 10 mol%) followed by DCE (2.0 mL) at r.t. and the reaction mixture was stirred at 80 °C for 20 h. To the cooled reaction mixture at r.t., was added TfOH (755 mg, 5.0 mmol) and stirring was continued at 80 °C for 15 h. Purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc, 99:1 to 94:6) furnished 4de.

Yield: 92.4 mg (69%); yellow solid; TLC (petroleum ether/EtOAc, 94:06; UV detection): Rf = 0.6 (1d), 0.5 (4de).

1H NMR (CDCl3, 400 MHz): δ = 7.39 (s, 1 H, Ar-H), 7.26–7.16 (m, 2 H, Ar-H), 7.15 (s, 1 H, Ar-H), 6.94 (s, 1 H, Ar-H), 3.98 (s, 3 H, ArOCH3), 3.89 (s, 3 H, ArOCH3), 2.62 (q, J =7.5 Hz, 2 H, CH 2CH3), 1.22 (t, J =7.5 Hz, 2 H, CH2CH 3).

13C NMR (CDCl3, 100 MHz): δ = 193.5 (C=O), 154.5 (s, Ar-C), 149.3 (s, Ar-C), 144.8 (s, Ar-C), 141.5 (s, Ar-C), 139.8 (s, Ar-C), 135.1 (s, Ar-C), 133.4 (d, Ar-CH), 126.9 (s, Ar-C), 123.4 (d, Ar-CH), 119.0 (d, Ar-CH), 107.1 (d, Ar-CH), 103.2 (d, Ar-CH), 56.3 (q, ArOCH3), 56.2 (q, ArOCH3), 28.7 (t, CH2), 15.3 (q, CH3).

HRMS (APCI+): m/z [M + H]+ calcd for [C17H17O3]+: 269.1172; found: 269.1166.


#

2-Fluoro-7-methyl-9H-fluoren-9-one (4ed)

In an oven-dried Schlenk tube, were added ethyl 2-bromobenzoate 1e (123.5 mg, 0.5 mmol), arylboronic acid 2d (75 mg, 0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol%), K2CO3 (138 mg, 1.0 mmol), and TBAI (16 mg, 10 mol%) followed by DCE (2.0 mL) at r.t. and the reaction mixture was stirred at 80 °C for 20 h. To the cooled reaction mixture at r.t., was added TfOH (755 mg, 5.0 mmol) and stirring was continued at 80 °C for 15 h. Purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc, 99:1 to 95:5) furnished 4ed.

Yield: 87.0 mg (82%); yellow solid; TLC (petroleum ether/EtOAc, 95:05; UV detection): Rf = 0.8 (1e), 0.6 (4ed).

1H NMR (CDCl3, 400 MHz): δ = 7.43 (s, 1 H, Ar-H), 7.42–7.36 (m, 1 H, Ar-H), 7.32 (d, J = 7.8 Hz, 1 H, Ar-H), 7.32–7.23 (m, 2 H, Ar-H), 7.11 (ddd, J = 8.8, 8.3, 2.4 Hz, 1 H, Ar-H), 2.35 (s, 3 H, ArCH3).

13C NMR (CDCl3, 100 MHz): δ = 192.7 (s, C=O), 163.2 (d, J = 248.7 Hz, Ar-C), 141.3 (s, Ar-C), 140.4 (s, Ar-C), 138.9 (s, Ar-C), 136.3 (d, J = 7.3 Hz, Ar-C), 135.4 (d, Ar-CH), 134.5 (s, Ar-C), 125.3 (d, Ar-CH), 121.1 (d, J = 8.1 Hz, Ar-CH), 120.7 (d, J = 23.0 Hz, Ar-CH), 119.9 (d, Ar-CH), 111.8 (d, J = 23.0 Hz, Ar-CH), 21.3 (d, ArCH3).

HRMS (APCI+): m/z [M + H]+ calcd for [C14H10FO]+: 213.0710; found: 213.0693.


#

2,3-Dimethoxy-9-methyl-9H-fluorene (8ag)

In an oven-dried Schlenk tube, were added 2-bromophenylketone 5a (100 mg, 0.5 mmol), arylboronic acid 2g (100 mg, 0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol%) and K2CO3 (138 mg, 1.0 mmol) followed by DMF at r.t. and the reaction mixture was stirred at 80 °C for 20 h. Then, to the cooled reaction mixture at ice temperature, was added NaBH4 (76 mg, 2 mmol) and stirring was continued at the same temperature for 0.5 h. After work-up, to the crude reaction mixture at ice temperature, were added DCE and BF3·OEt2 (710 mg, 5 mmol) and stirring was continued for 1 h. Progress of the reaction for the formation of 2,3-dimethoxy-9-methyl-9H-fluorene 8ag was monitored by TLC. The reaction mixture was then quenched with aq. NaHCO3, and the mixture was diluted with aq. NH4Cl and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with saturated aq. NaCl, dried (Na2SO4) and filtered. Evaporation of the solvent under reduced pressure and purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc, 99:1 to 95:5) furnished the product 8ag.

Yield: 100 mg (82%); white solid; TLC (petroleum ether/EtOAc, 93:07; UV detection): Rf = 0.8 (5a), 0.6 (8ag).

1H NMR (CDCl3, 400 MHz): δ = 7.62 (d, J = 7.4 Hz, 1 H, Ar-H), 7.44 (d, J = 7.3 Hz, 1 H, Ar-H), 7.32 (dd, J = 7.3, 7.3 Hz, 1 H, Ar-H), 7.24 (s, 1 H, Ar-H), 7.29 (ddd, J = 7.4, 7.3, 1 Hz, 1 H, Ar-H), 7.02 (s, 1 H, Ar-H), 3.97 (s, 3 H, ArOCH3), 3.94 (s, 3 H, ArOCH3), 3.83 (q, J = 7.4 Hz, CH), 1.48 (d, J = 7.4 Hz, 3 H, CH3).

13C NMR (CDCl3, 100 MHz): δ = 149.0 (s, Ar-C), 148.9 (s, Ar-C), 148.7 (s, Ar-C), 141.5 (s, Ar-C), 140.8 (s, Ar-C), 132.8 (s, Ar-C), 126.8 (d, Ar-CH), 125.6 (d, Ar-CH), 123.7 (d, Ar-CH), 118.8 (d, Ar-CH), 107.3 (d, Ar-CH), 103.0 (d, Ar-CH), 56.1 (q, ArOCH3), 56.0 (q, ArOCH3), 42.2 (d, CH), 18.3 (q, CH3).

HRMS (APCI+): m/z [M + H]+ calcd for [C16H17O2]+: 241.1223; found: 241.1209.


#

2,7-Dimethoxy-9-methyl-9H-fluorene (8bf)

In an oven-dried Schlenk tube, were added 2-bromophenylketone 5b (115 mg, 0.5 mmol), arylboronic acid 2f (84 mg, 0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol%) and K2CO3 (138 mg, 1.0 mmol) followed by DMF at r.t. and the reaction mixture was stirred at 80 °C for 20 h. Then, to the cooled reaction mixture at ice temperature, was added NaBH4 (76 mg, 2 mmol) and stirring was continued at the same temperature for 0.5 h. After work-up, to the crude reaction mixture at ice temperature, were added DCE and BF3·OEt2 (710 mg, 5 mmol) and the mixture was stirred for 1 h. Progress of the reaction for the formation of 2,7-dimethoxy-9-methyl-9H-fluorene 8bf was monitored by TLC. The reaction was then quenched with aq. NaHCO3, and the mixture was diluted with aq. NH4Cl and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with saturated aq. NaCl, dried (Na2SO4), and filtered. Evaporation of the solvent under reduced pressure and purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc, 99:1 to 95:5) furnished 8bf.

Yield: 99 mg (82%); colourless solid; TLC (petroleum ether/EtOAc, 92:08; UV detection): Rf = 0.8 (5b), 0.7 (8bf).

1H NMR (CDCl3, 400 MHz): δ = 7.54 (d, J = 8.3 Hz, 2 × 1 H, Ar-H), 7.01 (d, J = 2.1 Hz, 2 × 1 H, Ar-H), 6.88 (dd, J = 8.3, 2.4 Hz, 2 × 1 H, Ar-H), 3.85 (s, 2 × 3 H, ArOCH3), 3.90–3.84 (m, 1 H, CH), 1.49 (d, J = 7.4 Hz, 3 H, CH3).

13C NMR (CDCl3, 100 MHz): δ = 158.6 (s, 2 × Ar-C), 150.4 (s, 2 × Ar-C), 133.5 (s, 2 × Ar-C), 119.6 (d, 2 × Ar-CH), 112.6 (d, 2 × Ar-CH), 109.8 (d, 2 × Ar-CH), 55.5 (q, 2 × ArOCH3), 42.5 (d, CH), 18.5 (q, CH3).

HRMS (APCI+): m/z [M + H]+ calcd for [C16H17O2]+: 241.1223; found: 241.1229.


#

2,3,7-Trimethoxy-9-methyl-9H-fluorene (8bg)

In an oven-dried Schlenk tube, were added 2-bromophenylketone 5b (115 mg, 0.5 mmol), arylboronic acid 2g (100 mg, 0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol%) and K2CO3 (138 mg, 1.0 mmol) followed by DMF at r.t. and the reaction mixture was stirred at 80 °C for 20 h. Then, to the cooled reaction mixture at ice temperature, was added NaBH4 (76 mg, 2 mmol) and stirring was continued at the same temperature for 0.5 h. After work-up, to the crude reaction mixture at ice temperature, were added DCE and BF3·OEt2 (710 mg, 5 mmol) and stirring was continued for 1 h. Progress of the reaction for the formation of 2,3,7-trimethoxy-9-methyl-9H-fluorene 8bg was monitored by TLC. The reaction was then quenched with aq. NaHCO3, and the mixture was diluted with aq. NH4Cl and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with saturated aq. NaCl, dried (Na2SO4) and filtered. Evaporation of the solvent under reduced pressure and purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc, 99:1 to 92:8) furnished 8bg.

Yield: 116 mg (85%); colourless solid; TLC (petroleum ether/EtOAc, 92:08; UV detection): Rf = 0.7 (5b), 0.4 (8bg).

1H NMR (CDCl3, 400 MHz): δ = 7.50 (d, J = 8.3 Hz, 1 H, Ar-H), 7.17 (s, 1 H, Ar-H), 7.02 (d, J = 2.2 Hz, 1 H, Ar-H), 7.00 (s, 1 H, Ar-H), 6.87 (dd, J = 8.3, 2.3 Hz, 1 H, Ar-H), 3.96 (s, 3 H, ArOCH3), 3.93 (s, 3 H, ArOCH3), 3.85 (s, 3 H, ArOCH3), 3.82 (q, J = 7.4 Hz, 1 H, CH), 1.48 (d, J = 7.4 Hz, 3 H, CH3).

13C NMR (CDCl3, 100 MHz): δ = 158.6 (s, Ar-C), 150.9 (s, Ar-C), 148.7 (s, Ar-C), 148.1 (s, Ar-C), 140.8 (s, Ar-C), 133.8 (s, Ar-C), 133.0 (s, Ar-C), 119.3 (d, Ar-CH), 112.3 (d, Ar-CH), 110.0 (d, Ar-CH), 107.5 (d, Ar-CH), 102.6 (d, Ar-CH), 56.1 (q, ArOCH3), 56.1 (q, ArOCH3), 55.4 (q, ArOCH3), 42.2 (d, CH), 18.4 (q, CH3).

HRMS (APCI+): m/z [M + H]+ calcd for [C17H19O3]+: 271.1329; found: 271.1324.


#

9-Ethyl-2,3,7-trimethoxy-9H-fluorene (8cf)

In an oven-dried Schlenk tube, were added 2-bromophenylketone 5c (137 mg, 0.5 mmol), arylboronic acid 2f (84 mg, 0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol%) and K2CO3 (138 mg, 1.0 mmol) followed by DMF at r.t. and the reaction mixture was stirred at 80 °C for 20 h. Then, to the cooled reaction mixture at ice temperature, was added NaBH4 (76 mg, 2 mmol) and the mixture was stirred at the same temperature for 0.5 h. After work-up, to the crude reaction mixture at ice temperature, were added DCE and BF3·OEt2 (710 mg, 5 mmol) and stirring was continued for 1 h. Progress of the reaction for the formation of 9-ethyl-2,3,7-trimethoxy-9H-fluorene 8cf was monitored by TLC. The reaction was then quenched with aq. NaHCO3, and the mixture was diluted with aq. NH4Cl and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with saturated aq. NaCl, dried (Na2SO), and filtered. Evaporation of the solvent under reduced pressure and purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc, 99:1 to 92:8) furnished 8cf.

Yield: 103 mg (72%); colourless solid; TLC (petroleum ether/EtOAc, 95:05; UV detection): Rf = 0.6 (5c), 0.8 (8cf).

1H NMR (CDCl3, 400 MHz): δ = 7.51 (d, J = 8.2 Hz, 1 H, Ar-H), 7.16 (s, 1 H, Ar-H), 7.02 (d, J = 2.5 Hz, 1 H, Ar-H), 7.00 (s, 1 H, Ar-H), 6.88 (dd, J = 8.2, 2.8 Hz, 1 H, Ar-H), 3.96 (s, 3 H, ArOCH3), 3.93 (s, 3 H, ArOCH3), 3.91–3.84 (m, 1 H, CH), 3.85 (s, 3 H, ArOCH3), 2.10–1.99 (m, 2 H, CH 2CH3), 0.68 (t, J = 7.4 Hz, 3 H, CH2CH 3).

13C NMR (CDCl3, 100 MHz): δ = 158.5 (s, Ar-C), 149.1 (s, Ar-C), 148.7 (s, Ar-C), 148.0 (s, Ar-C), 139.0 (s, Ar-C), 134.7 (s, Ar-C), 133.9 (s, Ar-C), 119.2 (d, Ar-CH), 112.3 (d, Ar-CH), 110.4 (d, Ar-CH), 107.8 (d, Ar-CH), 102.4 (d, Ar-CH), 56.2 (q, ArOCH3), 56.1 (q, ArOCH3), 55.6 (q, ArOCH3), 48.3 (d, CH), 25.8 (t, CH2 CH3), 9.4 (q, CH2 CH 3).

HRMS (APCI+): m/z [M + H]+ calcd for [C18H21O3]+: 285.1485; found: 285.1466.


#

2-Ethyl-9-phenyl-9H-fluorene (8ee)

In an oven-dried Schlenk tube, were added 2-bromophenylketone 5e (131 mg, 0.5 mmol), arylboronic acid 2f (84 mg, 0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol%) and K2CO3 (138 mg, 1.0 mmol) followed by DMF at r.t. and the reaction mixture was stirred at 80 °C for 20 h. Then, to the cooled reaction mixture at ice temperature, was added NaBH4 (76 mg, 2 mmol) and stirring was continued at the same temperature for 0.5 h. After work-up, to the crude reaction mixture at ice temperature, were added DCE and BF3·OEt2 (710 mg, 5 mmol) and stirring was continued for 1 h. Progress of the reaction for the formation of 2-ethyl-9-phenyl-9H-fluorene 8ee was monitored by TLC. The reaction was then quenched with aq. NaHCO3, and the mixture was diluted with aq. NH4Cl and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with saturated aq. NaCl, dried (Na2SO4), and filtered. Evaporation of the solvent under reduced pressure and purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc, 99:1 to 95:5) furnished 8ee.

Yield: 91 mg (67%); colourless solid; TLC (petroleum ether/EtOAc, 95:05; UV detection): Rf = 0.5 (5e), 0.7 (8ee).

1H NMR (CDCl3, 400 MHz): δ = 7.74 (d, J = 7.3 Hz, 1 H, Ar-H), 7.69 (d, J = 7.8 Hz, 1 H, Ar-H), 7.34 (dd, J = 7.3, 7.3 Hz, 1 H, Ar-H), 7.30–7.16 (m, 6 H, Ar-H), 7.14 (s, 1 H, Ar-H), 7.16–7.03 (m, 2 H, Ar-H), 4.99 (s, 1 H, CH), 2.63 (q, J = 7.8 Hz, 2 H, CH 2CH3), 1.20 (t, J = 7.8 Hz, 3 H, CH2CH 3).

13C NMR (CDCl3, 100 MHz): δ = 148.2 (s, Ar-C), 147.9 (s, Ar-C), 143.8 (s, Ar-C), 141.9 (s, Ar-C), 141.1 (s, Ar-C), 138.7 (s, Ar-C), 128.7 (d, 2C, 2 × Ar-CH), 128.4 (d, 2C, 2 × Ar-CH), 127.3 (d, Ar-CH), 127.1 (d, Ar-C), 126.9 (d, Ar-CH), 126.8 (d, Ar-CH), 125.3 (d, Ar-CH), 124.9 (d, Ar-CH), 119.7 (d, Ar-CH), 119.6 (d, Ar-CH), 54.4 (d, CH), 29.1 (t, CH 2CH3), 15.9 (q, CH2 CH3).

HRMS (APCI+): m/z [M+NH4]+ calcd for [C21H22N]+: 288.1747; found: 288.1752.


#

2,3-Dimethoxy-9-phenyl-9H-fluorene (8eg)

In an oven-dried Schlenk tube, were added 2-bromophenylketone 5e (131 mg, 0.5 mmol), arylboronic acid 2g (100 mg, 0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol%) and K2CO3 (138 mg, 1.0 mmol) followed by DMF at r.t. and the reaction mixture stirred at 80 °C for 20 h. Then, to the cooled reaction mixture at ice temperature, was added NaBH4 (76 mg, 2 mmol) and stirring was continued at the same temperature for 0.5 h. After work-up, to the crude reaction mixture at ice temperature, were added DCE and BF3·OEt2 (710 mg, 5 mmol) and stirring was continued for 1 h. Progress of the reaction for the formation of 2,3-dimethoxy-9-phenyl-9H-fluorene 8eg was monitored by TLC. The reaction was then quenched with aq. NaHCO3, and the mixture was diluted with aq. NH4Cl and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with saturated aq. NaCl, dried (Na2SO), and filtered. Evaporation of the solvent under reduced pressure and purification of the crude material by silica gel column chromatography (petroleum ether/EtOAc, 99:1 to 95:5) furnished 8eg.

Yield: 134 mg (88%); colourless solid; TLC (petroleum ether/EtOAc, 95:05; UV detection): Rf = 0.5 (5e), 0.4 (8eg).

1H NMR (CDCl3, 400 MHz): δ = 7.66 (d, J = 7.8 Hz, 1 H, Ar-H), 7.33 (dd, J = 7.3, 7.3 Hz, 1 H, Ar-H), 7.30–7.16 (m, 5 H, Ar-H), 7.16 (dd, J = 7.3, 7.3 Hz, 1 H, Ar-H), 7.09 (s, 1 H, Ar-H), 7.08 (d, J = 7.3 Hz, 1 H, Ar-H), 6.82 (s, 1 H, Ar-H), 4.93 (s, 1 H, CH), 3.99 (s, 3 H, ArOCH3), 3.81 (s, 3 H, ArOCH3).

13C NMR (CDCl3, 100 MHz): δ = 149.2 (s, Ar-C), 149.1 (s, Ar-C), 148.1 (s, Ar-C), 141.7 (s, Ar-C), 141.2 (s, Ar-C), 140.3 (s, Ar-C), 133.6 (s, Ar-C), 128.7 (d, 2C, 2 × Ar-CH), 128.2 (d, 2C, 2 × Ar-CH), 127.2 (d, Ar-C), 126.8 (d, Ar-CH), 126.0 (d, Ar-CH), 125.0 (d, Ar-CH), 118.7 (d, Ar-CH), 108.3 (d, Ar-CH), 102.8 (d, Ar-CH), 56.1 (q, ArOCH3), 56.0 (q, ArOCH3), 54.3 (d, CH).

HRMS (APCI+): m/z [M + H]+ calcd for [C21H19O2]+: 303.1380; found: 303.1361.


#
#

Supporting Information

  • References

    • 1a Tietze LF. Chem. Rev. 1996; 96: 115
    • 1b Tietze LF, Beifuss U. Angew. Chem. 1993; 105: 137
    • 1c Kishi Y. Pure Appl. Chem. 1993; 65: 771
    • 1d Suh EM, Kishi Y. J. Am. Chem. Soc. 1994; 116: 11205
    • 2a Capodilupo A, Vergaro V, Accorsi G, Fabiano E, Baldassarre F, Anna G, Gigli G, Ciccarella G. Tetrahedron 2016; 72: 2920
    • 2b Chi S, Li L, Wu Y. J. Phys. Chem. 2016; 120: 13706
    • 2c Tian X, Ren F, Zhao B, Ren Y, Zhao S, Wang J. Catal. Commun. 2018; 106: 44
    • 2d Thangadurai D, Nithya I, Manjubaashini N, Bhuvanesh N, Bharathi G, Nandhakumar R, Nataraj D. Spectrochim. Acta, Part A . 2018; 465
  • 3 Shi Y, Gao S. Tetrahedron 2016; 1717
    • 4a Okpekon T, Millot M, Champy P, Gleye C, Yolou S, Bories C, Loiseau P, Laurens A, Hocquemiller R. Nat. Prod. Res. 2009; 23: 909
    • 4b Fu J.-M, Zhao B.-P, Sharp M, Snieckus V. Can. J. Chem. 1994; 72: 227
    • 4c Cone MC, Melville CR, Gore MP, Gould SJ. J. Org. Chem. 1993; 58: 1058
    • 4d Nicolaou K, Hale CR, Nilewski C, Ioannidou HA. Chem. Soc. Rev. 2012; 41: 5185
    • 4e Fieser LF, Fieser M. Natural Products Related To Phenanthrene. 3rd. Ed. . Reinhold Publishing Corporation; New York: 1949
    • 5a Barluenga J, Trincado M, Rubio E, González JM. Angew. Chem. Int. Ed. 2006; 45: 3140
    • 5b Fukuyama T, Maetani S, Miyagawa K, Ryu I. Org. Lett. 2014; 16: 3216
    • 5c Nösel P, Moghimi S, Hendrich C, Haupt M, Rudolph M, Rominger F, Hashmia AS. K. Adv. Synth. Catal. 2014; 356: 3755
    • 5d Chen XY, Ozturk S, Sorensen EJ. Org. Lett. 2017; 19: 1140
    • 5e Wertz S, Leifert D, Studer A. Org. Lett. 2013; 15: 928
    • 5f Laha JK, Jethava KP, Patel S. Org. Lett. 2015; 17: 5890
    • 5g Prashad M, Liu Y, Mak XY, Har D, Repič O, Blacklock TJ. Tetrahedron Lett. 2002; 43: 8559
    • 5h Gao Q, Xu S. Org. Biomol. Chem. 2018; 16: 208
    • 5i Fukuyama T, Maetani S, Miyagawa K, Ryu I. Org. Lett. 2014; 16: 3216
    • 5j Liu T.-P, Liao Y.-X, Xing C.-H, Hu Q.-S. Org. Lett. 2011; 13: 2452
    • 6a Hwang SJ, Cho SH, Chang S. J. Am. Chem. Soc. 2008; 130: 16158
    • 6b Rathore R, Chebny VJ, Abdelwahed SH. J. Am. Chem. Soc. 2005; 127: 8012
    • 6c Chiang C.-L, Shu C.-F, Chen C.-T. Org. Lett. 2005; 7: 3717
    • 6d Romain M, Tondelier D, Vanel JC, Geffroy B, Jeannin O, Rault-Berthelot J, Métivier R, Poriel C. Angew. Chem. Int. Ed. 2013; 52: 14147
    • 6e Sarkar S, Maiti S, Bera K, Jalal S, Jana U. Tetrahedron Lett. 2012; 53: 5544
    • 6f Chandrasekhar V, Suriya Narayanan R, Thilagar P. Organometallics 2009; 28: 5883
    • 6g Shen X, Gu N, Liu P, Ma X, Xie J, Liu Y, He L, Dai B. RSC Adv. 2015; 5: 63726
    • 7a Mishra K, Pandey AK, Singh JB, Singh RM. Org. Biomol. Chem. 2016; 14: 6328
    • 7b Tang J, Zhao S, Wei Y, Quan Z, Huo C. Org. Biomol. Chem. 2017; 15: 1589
    • 8a Gandeepan P, Hung C.-H, Cheng C.-H. Chem. Commun. 2012; 9379
    • 8b Li H, Zhu R.-Y, Shi W.-J, He K.-H, Shi Z.-J. Org. Lett. 2012; 14: 4850
    • 8c Wan J.-C, Huang J.-M, Jhan Y.-H, Hsieh J.-C. Org. Lett. 2013; 15: 2742
    • 9a Campo MA, Larock RC. J. Org. Chem. 2002; 67: 5616
    • 9b Furusawa T, Morimoto T, Oka N, Tanimoto H, Nishiyama Y, Kakiuchi K. Chem. Lett. 2016; 45: 406
  • 10 Pünner F, Schieven J, Hilt G. Org. Lett. 2013; 15: 4888
    • 11a Reddy PV, Karegoudar T, Monisha T, Nayak AS. Int. Biodeterior. Biodegrad. 2017; 123: 156
    • 11b George SR, Elton TE, Harper JB. Org. Biomol. Chem. 2015; 13: 10745
    • 12a Sreenivasulu C, Reddy AG. K, Satyanarayana G. Org. Chem. Front. 2017; 4: 972
    • 12b Das A, Gopi Krishna Reddy A, Satyanarayana G. RSC Adv. 2014; 4: 26662
    • 12c Ramulu BV, Satyanarayana G. RSC Adv. 2015; 5: 70972
    • 12d Krishna J, Niharika P, Satyanarayana G. RSC Adv. 2015; 5: 26749
    • 12e Mahendar L, Satyanarayana G. RSC Adv. 2016; 6: 20588
  • 13 Liu Z, Tan H, Wang L, Fu T, Xia Y, Zhang Y, Wang J. Angew. Chem. 2015; 127: 3099
  • 14 Das T, Chakraborty A, Sarkar A. Tetrahedron Lett. 2014; 55: 5174
    • 15a Reddy AG. K, Satyanarayana G. J. Org. Chem. 2016; 81: 12212
    • 15b Niharika P, Ramulu BV, Satyanarayana G. ACS Omega 2018; 3: 218
    • 15c Suchand B, Satyanarayana G. J. Org. Chem. 2016; 81: 6409
    • 15d Suchand B, Satyanarayana G. Eur. J. Org. Chem. 2018; 2233
    • 15e Sreenivasulu C, Satyanarayana G. Eur. J. Org. Chem. 2018; 2846
    • 16a Ravi Kumar D, Satyanarayana G. Org. Lett. 2015; 17: 5894
    • 16b Kumar DR, Satyanarayana G. ChemistrySelect 2018; 3: 7867
  • 17 Ramulu BV, Reddy AG. K, Satyanarayana G. Synlett 2013; 24: 868
  • 18 Niharika P, Ramulu BV, Satyanarayana G. Org. Biomol. Chem. 2014; 12: 4347
  • 19 Niharika P, Satyanarayana G. Eur. J. Org. Chem. 2018; 971
    • 20a Rana N, Niharika P, Kishore DR, Satyanarayana G. ChemistrySelect 2017; 2: 10809
    • 20b Reddy AG. K, Krishna J, Satyanarayana G. ChemistrySelect 2016; 1: 1151
    • 21a Guijie L, Erjuan W, Haoyi C, Hongfeng L, Yuanhong L, Peng GW. Tetrahedron 2008; 64: 9033
    • 21b Konishi H, Futamata S, Wang X, Manabe K. Adv. Synth. Catal. 2018; 360: 1805
    • 21c Ciske FL, Jones WD. Jr. Synthesis 1998; 1195
    • 21d Liu L, Wang F, Li Z, Wang J. Asian J. Org. Chem. 2014; 3: 695
    • 21e Corrie TJ, Ball LT, Russell CA, Lloyd-Jones GC. J. Am. Chem. Soc. 2016; 139: 245
    • 21f Klemm LH, Huber E, Klopfenstein CE. J. Org. Chem. 1964; 29: 1960
    • 21g Sarkar S, Tadigoppula N. RSC Adv. 2014; 4: 40964
    • 21h Zhao J, Yue D, Campo MA, Larock RC. J. Am. Chem. Soc. 2007; 129: 5288

  • References

    • 1a Tietze LF. Chem. Rev. 1996; 96: 115
    • 1b Tietze LF, Beifuss U. Angew. Chem. 1993; 105: 137
    • 1c Kishi Y. Pure Appl. Chem. 1993; 65: 771
    • 1d Suh EM, Kishi Y. J. Am. Chem. Soc. 1994; 116: 11205
    • 2a Capodilupo A, Vergaro V, Accorsi G, Fabiano E, Baldassarre F, Anna G, Gigli G, Ciccarella G. Tetrahedron 2016; 72: 2920
    • 2b Chi S, Li L, Wu Y. J. Phys. Chem. 2016; 120: 13706
    • 2c Tian X, Ren F, Zhao B, Ren Y, Zhao S, Wang J. Catal. Commun. 2018; 106: 44
    • 2d Thangadurai D, Nithya I, Manjubaashini N, Bhuvanesh N, Bharathi G, Nandhakumar R, Nataraj D. Spectrochim. Acta, Part A . 2018; 465
  • 3 Shi Y, Gao S. Tetrahedron 2016; 1717
    • 4a Okpekon T, Millot M, Champy P, Gleye C, Yolou S, Bories C, Loiseau P, Laurens A, Hocquemiller R. Nat. Prod. Res. 2009; 23: 909
    • 4b Fu J.-M, Zhao B.-P, Sharp M, Snieckus V. Can. J. Chem. 1994; 72: 227
    • 4c Cone MC, Melville CR, Gore MP, Gould SJ. J. Org. Chem. 1993; 58: 1058
    • 4d Nicolaou K, Hale CR, Nilewski C, Ioannidou HA. Chem. Soc. Rev. 2012; 41: 5185
    • 4e Fieser LF, Fieser M. Natural Products Related To Phenanthrene. 3rd. Ed. . Reinhold Publishing Corporation; New York: 1949
    • 5a Barluenga J, Trincado M, Rubio E, González JM. Angew. Chem. Int. Ed. 2006; 45: 3140
    • 5b Fukuyama T, Maetani S, Miyagawa K, Ryu I. Org. Lett. 2014; 16: 3216
    • 5c Nösel P, Moghimi S, Hendrich C, Haupt M, Rudolph M, Rominger F, Hashmia AS. K. Adv. Synth. Catal. 2014; 356: 3755
    • 5d Chen XY, Ozturk S, Sorensen EJ. Org. Lett. 2017; 19: 1140
    • 5e Wertz S, Leifert D, Studer A. Org. Lett. 2013; 15: 928
    • 5f Laha JK, Jethava KP, Patel S. Org. Lett. 2015; 17: 5890
    • 5g Prashad M, Liu Y, Mak XY, Har D, Repič O, Blacklock TJ. Tetrahedron Lett. 2002; 43: 8559
    • 5h Gao Q, Xu S. Org. Biomol. Chem. 2018; 16: 208
    • 5i Fukuyama T, Maetani S, Miyagawa K, Ryu I. Org. Lett. 2014; 16: 3216
    • 5j Liu T.-P, Liao Y.-X, Xing C.-H, Hu Q.-S. Org. Lett. 2011; 13: 2452
    • 6a Hwang SJ, Cho SH, Chang S. J. Am. Chem. Soc. 2008; 130: 16158
    • 6b Rathore R, Chebny VJ, Abdelwahed SH. J. Am. Chem. Soc. 2005; 127: 8012
    • 6c Chiang C.-L, Shu C.-F, Chen C.-T. Org. Lett. 2005; 7: 3717
    • 6d Romain M, Tondelier D, Vanel JC, Geffroy B, Jeannin O, Rault-Berthelot J, Métivier R, Poriel C. Angew. Chem. Int. Ed. 2013; 52: 14147
    • 6e Sarkar S, Maiti S, Bera K, Jalal S, Jana U. Tetrahedron Lett. 2012; 53: 5544
    • 6f Chandrasekhar V, Suriya Narayanan R, Thilagar P. Organometallics 2009; 28: 5883
    • 6g Shen X, Gu N, Liu P, Ma X, Xie J, Liu Y, He L, Dai B. RSC Adv. 2015; 5: 63726
    • 7a Mishra K, Pandey AK, Singh JB, Singh RM. Org. Biomol. Chem. 2016; 14: 6328
    • 7b Tang J, Zhao S, Wei Y, Quan Z, Huo C. Org. Biomol. Chem. 2017; 15: 1589
    • 8a Gandeepan P, Hung C.-H, Cheng C.-H. Chem. Commun. 2012; 9379
    • 8b Li H, Zhu R.-Y, Shi W.-J, He K.-H, Shi Z.-J. Org. Lett. 2012; 14: 4850
    • 8c Wan J.-C, Huang J.-M, Jhan Y.-H, Hsieh J.-C. Org. Lett. 2013; 15: 2742
    • 9a Campo MA, Larock RC. J. Org. Chem. 2002; 67: 5616
    • 9b Furusawa T, Morimoto T, Oka N, Tanimoto H, Nishiyama Y, Kakiuchi K. Chem. Lett. 2016; 45: 406
  • 10 Pünner F, Schieven J, Hilt G. Org. Lett. 2013; 15: 4888
    • 11a Reddy PV, Karegoudar T, Monisha T, Nayak AS. Int. Biodeterior. Biodegrad. 2017; 123: 156
    • 11b George SR, Elton TE, Harper JB. Org. Biomol. Chem. 2015; 13: 10745
    • 12a Sreenivasulu C, Reddy AG. K, Satyanarayana G. Org. Chem. Front. 2017; 4: 972
    • 12b Das A, Gopi Krishna Reddy A, Satyanarayana G. RSC Adv. 2014; 4: 26662
    • 12c Ramulu BV, Satyanarayana G. RSC Adv. 2015; 5: 70972
    • 12d Krishna J, Niharika P, Satyanarayana G. RSC Adv. 2015; 5: 26749
    • 12e Mahendar L, Satyanarayana G. RSC Adv. 2016; 6: 20588
  • 13 Liu Z, Tan H, Wang L, Fu T, Xia Y, Zhang Y, Wang J. Angew. Chem. 2015; 127: 3099
  • 14 Das T, Chakraborty A, Sarkar A. Tetrahedron Lett. 2014; 55: 5174
    • 15a Reddy AG. K, Satyanarayana G. J. Org. Chem. 2016; 81: 12212
    • 15b Niharika P, Ramulu BV, Satyanarayana G. ACS Omega 2018; 3: 218
    • 15c Suchand B, Satyanarayana G. J. Org. Chem. 2016; 81: 6409
    • 15d Suchand B, Satyanarayana G. Eur. J. Org. Chem. 2018; 2233
    • 15e Sreenivasulu C, Satyanarayana G. Eur. J. Org. Chem. 2018; 2846
    • 16a Ravi Kumar D, Satyanarayana G. Org. Lett. 2015; 17: 5894
    • 16b Kumar DR, Satyanarayana G. ChemistrySelect 2018; 3: 7867
  • 17 Ramulu BV, Reddy AG. K, Satyanarayana G. Synlett 2013; 24: 868
  • 18 Niharika P, Ramulu BV, Satyanarayana G. Org. Biomol. Chem. 2014; 12: 4347
  • 19 Niharika P, Satyanarayana G. Eur. J. Org. Chem. 2018; 971
    • 20a Rana N, Niharika P, Kishore DR, Satyanarayana G. ChemistrySelect 2017; 2: 10809
    • 20b Reddy AG. K, Krishna J, Satyanarayana G. ChemistrySelect 2016; 1: 1151
    • 21a Guijie L, Erjuan W, Haoyi C, Hongfeng L, Yuanhong L, Peng GW. Tetrahedron 2008; 64: 9033
    • 21b Konishi H, Futamata S, Wang X, Manabe K. Adv. Synth. Catal. 2018; 360: 1805
    • 21c Ciske FL, Jones WD. Jr. Synthesis 1998; 1195
    • 21d Liu L, Wang F, Li Z, Wang J. Asian J. Org. Chem. 2014; 3: 695
    • 21e Corrie TJ, Ball LT, Russell CA, Lloyd-Jones GC. J. Am. Chem. Soc. 2016; 139: 245
    • 21f Klemm LH, Huber E, Klopfenstein CE. J. Org. Chem. 1964; 29: 1960
    • 21g Sarkar S, Tadigoppula N. RSC Adv. 2014; 4: 40964
    • 21h Zhao J, Yue D, Campo MA, Larock RC. J. Am. Chem. Soc. 2007; 129: 5288

Zoom Image
Scheme 1 Synthesis of fluorenones 4aaef from 1ae and 2ag. Reaction conditions: 2-bromoethyl benzoate 1ae (0.5 mmol), arylboronic acid 2ag (0.55 mmol), Pd(OAc)2 (6 mg, 5 mol%), K2CO3 (138 mg, 1.0 mmol), TBAI (16 mg, 10 mol%), DCE (2 mL), 100 °C, 15 h. After confirming formation of the Suzuki product, TfOH (10 equiv) was added at 0 °C and the mixture was stirred at room temperature. Yields in parentheses are isolated yields of chromatographically pure products.
Zoom Image
Scheme 2 Synthesis of fluorenes 8adeg from 2ag and 5af. Reaction conditions: (i) Pd(OAc)2, TBAI, K2CO3, DMF, 80 °C, 24 h; (ii) NaBH4, 0 °C to r.t., 0.5 h; (iii) BF3·OEt2, DCE (2 mL), 0 °C to r.t. Reactions were performed with 2-bromo ketones 5ae (0.5 mmol), arylboronic acid 2ag (0.55 mmol), Pd(OAc)2 (5.6 mg, 5 mol %), K2CO3 (138 mg, 1.0 mmol), TBAI (16 mg, 10 mol %), DCE (2 mL), 100 °C, 15 h, after confirming formation of the Suzuki product, NaBH4 (37.8 mg, 1.0 mmol) was added at 0 °C then the reaction mixture was stirred at room temperature for 0.5 h. After confirming formation of the corresponding alcohol, BF3·OEt2 was added to the worked up reaction mixture. Yields in the parentheses are isolated yields of chromatographically pure products.