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Synlett 2016; 27(03): 395-398
DOI: 10.1055/s-0035-1560527
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© Georg Thieme Verlag Stuttgart · New York

One-Pot Palladium(II)-Catalyzed Synthesis of Fluorenones via Decarboxylative Cyclization

Zhiqiang Cai*
School of Petrochemical Engineering, Shenyang University of Technology, Liaoyang 111003, P. R. of China   Email: kahongzqc@163.com
,
Xu Hou
School of Petrochemical Engineering, Shenyang University of Technology, Liaoyang 111003, P. R. of China   Email: kahongzqc@163.com
,
Ling Hou
School of Petrochemical Engineering, Shenyang University of Technology, Liaoyang 111003, P. R. of China   Email: kahongzqc@163.com
,
Zhiquan Hu
School of Petrochemical Engineering, Shenyang University of Technology, Liaoyang 111003, P. R. of China   Email: kahongzqc@163.com
,
Bo Zhang
School of Petrochemical Engineering, Shenyang University of Technology, Liaoyang 111003, P. R. of China   Email: kahongzqc@163.com
,
Zhengsheng Jin
School of Petrochemical Engineering, Shenyang University of Technology, Liaoyang 111003, P. R. of China   Email: kahongzqc@163.com
› Author Affiliations
Further Information

Publication History

Received: 31 August 2015

Accepted after revision: 05 October 2015

Publication Date:
19 November 2015 (online)

 
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Abstract

A one-pot palladium-catalyzed synthesis of fluoronones via decarboxylative cyclization is reported. This protocol offers good yields and tolerates a broad range of functional groups. Based on the extensive experimental data, we propose a plausible decarboxylative insertion mechanism.


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Key words

palladium-catalyzed - decarboxylative insertion - C–C cleavage - control experiment - mechanism

Fluorenones are prominent structural motifs of many electronic and optical materials[1] and bioactive natural products.[2] Thus, intense efforts have focused on the development of novel methods to synthesize these compounds. Traditionally, they are synthesized by Friedel–Crafts acylation,[3] remote metalation,[4] and oxidation of fluorenes[5] or fluorenols.[6] Recently, some new metal-catalyzed strategies are reported, including radical cyclization,[7] coupling reactions of arylpalladium,[8] carbonylation,[9] and decarboxylation.[10]

Although diverse successful synthesis of fluorenones has been afforded, the scope of carbonyl source reported were always focused on acyl substrates and CO. More recently, carboxylic acids,[11] organic nitrile,[12] and aldoxime[13] were developed as new novel carbonyl source to attach fluorenones. In the catalytic system of organic nitrile[12] or aldoxime,[13] the carbonyl group was derived from the hydrolysis of C=N bonds. On the other hand, metal-catalyzed insertion of isocyanide[14] could form the similar C=N bonds, which inspired us that isocyanide may be a new carbonyl source in the synthesis of fluorenones. Herein, a one-pot palladium(II)-catalyzed synthesis of fluorenones via decarboxylative cyclization using tert-butyl isocyanide as a new carbonyl source is reported (Scheme [1]). The control experiments suggested a decarboxylative insertion mechanism.

Table 1 Optimization of the Conditions

Entrya

Catalyst (mol%)

Additive (equiv)

Yield (%)b

 1

Pd(OAc)2 (5)

–

<5

 2

Pd(OAc)2 (5)

AgOAc (2)

38

 3

Pd(OAc)2 (5)

Ag2CO3 (2)

74

 4

Pd(OAc)2 (5)

Ag2O (2)

57

 5

Pd(OAc)2 (5)

Cu(OAc)2 (2)

23

 6

Pd(OAc)2 (5)

K2S2O8 (2)

41

 7

Pd(OAc)2 (5)

BQ (2)

 0

 8

Pd(OAc)2 (5)

AcOH (2)

<5

 9

Pd(OAc)2 (5)

K2CO3

 0

10

Pd(OTf)2 (5)

Ag2CO3 (2)

80

11

PdCl2 (5)

Ag2CO3 (2)

36

12

Pd/C (5)

Ag2CO3 (2)

12

a Reaction conditions: 1a (0.5 mmol), tert-butyl isocyanide (1 mmol), catalyst (5 mol%), oxidant (1 mmol), DMSO (50% aq) 3 mL, 140 °C for 24 h.

b Isolated yields.

Zoom Image
Scheme 1 Metal-catalyzed insertion synthesis of fluorenones

We initiated our studies by using 2-phenylbenzoic acid (1a) and tert-butyl isocyanide as a model substrate (Table [1], entry 1), which was treated with 5 mol% of Pd(OAc)2 in DMSO (50% aq) at 140 °C for 24 hours. However, very poor yield (<5%) of 3a was afforded (Table [1], entry 1). When two equivalents of AgOAc were added, the yield increased to 38% (Table [1], entry 2), which suggested that oxidants might increase the yield. After studying other oxidants carefully, Ag2CO3 showed the best activity (Table [1], entries 3–7). The addition of acid or base did not give good results (Table [1], entries 8 and 9). Subsequently, screening of other palladium catalysts, Pd(OTf)2 gave the best catalytic efficiency, increasing the yield of 3a to 80% (Table [1], entries 10–12). The use of other solvents or increasing the amount of loading catalyst and additive led to no significant improvement on the yield (Supporting Information, SI-Tables 1, 2).

Zoom Image
Scheme 2 Exploring the utility of this transformation. Reagents and conditions: 1 (0.5 mmol), tert-butyl isocyanide (1 mmol), Pd(OTf)2 (5 mol%), Ag2CO3 (1 mmol), DMSO (50% aq) 3 mL, 140 °C for 24 h.

Encouraged by the preliminary results, we tried to explore the functional-group tolerance for the synthesis of fluorenones. The reaction showed a good tolerance to many functional groups, including electron-donating and electron-withdrawing groups (Scheme [2, 3a–p, e]. g., Me, OMe, Cl, Br, F, CF3). Benzoic acids with electron-donating groups on the 4- or/and 3-positions afforded the corresponding products in good to excellent yields (3a–e,g,m). But 2-substituted substrate resulted in a poor yield (3f, 36%), which might be due to steric hindrance. Notably, halogen substituents could also be tolerated in moderate yields (3h–j), which provided opportunities for further functionalization. However, benzoic acids with strong electron-withdrawing groups (3k,p) showed poor activity. In general, benzoic acids with electron-donating groups gave the better yields. Hetero- or nonaromatic substrates showed no activity (3q–t).

To gain some preliminary insight into the reaction mechanism, control experiments were employed as shown in Scheme [3]. Firstly, the reaction of 1a under standard conditions in the absence of isocyanide afforded 69% yield of xenene (Scheme [3], eq. 1). However, using the deuterated solvent (DMSO-d 6/D2O = 1:1) gave the appropriate deuterated xenene with D/H = 6.3:3.7 (Scheme [3], eq. 2). Secondly, the parallel reaction of 1a–d [5] in the absence of isocyanide at 140 °C and 50 °C afforded the appropriate deuterated xenene with D/H = 8.7:1.3 and D/H = 9.1:0.9, respectively (Scheme [3], eq. 3 and eq. 4). These results suggests a decarboxylation insertion mechanism via C–H activation.[15]

Based upon the experimental and literature results,[14] [15] a plausible mechanism is proposed in Scheme [4]. Firstly, the decarboxylation insertion of 1a catalyzed by the palladium/silver catalyst via two possible paths (path 1 or 2) generated intermediate III.[15] Subsequently, the domino elimination and hydrolysis of III (path a or path b) generated 3a to finish the catalytic cycle.[14]

Zoom Image
Scheme 3 Control experiments for the mechanism
Zoom Image
Scheme 4 The possible mechanism

In summary, we have developed a one-pot palladium(II)-catalyzed synthesis of fluorenones via decarboxylative cyclization using tert-butyl isocyanide as a new carbonyl source.[16] [17] This direct C–COOH cleavage and C–H activation is suitable for a broad range of substrates. The control experiments suggested a possible decarboxylative insertion mechanism. Further studies concerning the detailed mechanism and the broader scope of substrates are currently under way in our laboratory.


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Acknowledgment

This work was supported financially by the Scientific Research Foundation of the Education Department of Liaoning Province (L2015383) and the Doctoral Start-Up Fund of Shenyang University of Technology (No. 521422).

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org.accesdistant.sorbonne-universite.fr/10.1055/s-0035-1560527.
  • Supporting Information


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Zoom Image
Scheme 1 Metal-catalyzed insertion synthesis of fluorenones
Zoom Image
Scheme 2 Exploring the utility of this transformation. Reagents and conditions: 1 (0.5 mmol), tert-butyl isocyanide (1 mmol), Pd(OTf)2 (5 mol%), Ag2CO3 (1 mmol), DMSO (50% aq) 3 mL, 140 °C for 24 h.
Zoom Image
Scheme 3 Control experiments for the mechanism
Zoom Image
Scheme 4 The possible mechanism