Visible-light photoredox catalyzed synthesis of polysubstituted furfuryl trifluoroacetamide derivatives

Journal Pre-proof Visible-light photoredox catalyzed synthesis of polysubstituted furfuryl trifluoroacetamide derivatives Taotao Chen, Wei Wu, Zhiqiang Weng PII:

S0040-4020(19)31142-1

DOI:

https://doi.org/10.1016/j.tet.2019.130751

Reference:

TET 130751

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Tetrahedron

Received Date: 18 September 2019 Revised Date:

23 October 2019

Accepted Date: 25 October 2019

Please cite this article as: Chen T, Wu W, Weng Z, Visible-light photoredox catalyzed synthesis of polysubstituted furfuryl trifluoroacetamide derivatives, Tetrahedron (2019), doi: https://doi.org/10.1016/ j.tet.2019.130751. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.

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Visible-light photoredox catalyzed synthesis of polysubstituted furfuryl trifluoroacetamide derivatives

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Taotao Chen, Wei Wu, and Zhiqiang Weng ∗ R1

O R

2

R1

R

O

[Ru] cat.

+ H2N R3

CF3

2

O O CF3

Blue LEDs DCE, r.t.

NH R3

R1 R

2

O

R3

29 examples up to 98% yield

Tetrahedron journal homepage: www.elsevier.com

Visible-light photoredox catalyzed synthesis of polysubstituted furfuryl trifluoroacetamide derivatives Taotao Chen, Wei Wu, and Zhiqiang Weng * Fujian Provincial Key Laboratory of Electrochemical Energy Storage Materials, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.

ARTICLE INFO

ABSTRACT

Article history: Received Received in revised form Accepted Available online

A visible-light photoredox catalyzed reaction of enynones with 2,2,2-trifluoroacetamide to access polysubstituted furfuryl trifluoroacetamide derivatives under mild reaction conditions is reported. This transformation proceeds through the furan-substituted carbene intermediate, which subsequently undergoes an intermocular trapping process by 2,2,2-trifluoroacetamide to produce the desired furfuryl trifluoroacetamides.

Keywords: Photoredox-catalyzed Trifluoroacetamide Furan-substituted carbene Enynones Cyclization Fluorine

2009 Elsevier Ltd. All rights reserved.

1. Introduction Substituted furans are frequently found as core structures in many natural products,1 pharmacologically active compounds,2 and functional organic molecules.3 For example (Figure 1), the cyanoacrylates containing furan or tetrahydrofuran moieties shows promising herbicidal activities against dicotyledonous weeds;4 Bipinnatin J is a diterpene isolated from Pseudopterogorgia bipinnata,5 and this compound may well be a biosynthetic precursor to several cembrenolides; The furan derivative, plakorsin isolated from the Taiwanese marine sponge Plakortis simplex exhibits cytotoxic activity against COLO-250 and KB-16 cells;6 Nitrofurantoin is an antibiotic used to treat bladder infections.7 Owing to their broad spectrum of biological activities, the synthetic community has established some interesting strategies for the synthesis of substituted furans.8 In recent years, considerable efforts have been made toward the synthesis of polysubstituted furans in search of milder reaction conditions, more readily available starting molecules, and improving access to highly decorated furans. In this respect, enynones have emerged as readily accessible and versatile substrates and have been widely applied in many important transformations.9 Notable advances for the synthesis of polysubstituted furan derivatives are achieved by the reactions of ene-yne-ketones with various nucleophiles, such as aryl carboxylic acids,10 sulfinic acids,11 alcohols,12 azoles,12 −−−−−−−−−−−−−−−− * Corresponding authors. Tel./fax: +86 591 22866247; e-mail addresses: [email protected].

silanes,13 H-phosphonates,14 borane adducts.15 The schematic overall sequences of these types of reactions are shown in Scheme 1, and they involve the formation of either metal carbenoid intermediate (Scheme 1a) or sulfonium ylide (Scheme 1b). Some recent approaches to furans derivatives are also noteworthy.11,16

Figure 1. Structures of some furan cores containing biologically active molecules

Incorporation of fluorine atoms or fluorinated groups into organic molecules has become a powerful and widely employed tactic to improve lipophilicity, membrane permeability, metabolic stability and binding selectivity of drug-like molecules.17 In this context, compounds bearing 2,2,2-trifluoroacetamide group, such as flupyrimin, has

2

Tetrahedron

significant biological activities, including outstanding insecticidal potency to the resistant rice pests together with superior safety toward pollinators.18 Therefore, developing a telescoped procedure in which the furfuryl trifluoroacetamides can be synthesized in one-pot reaction from a benign precursor under mild conditions would enable their screening of new biological activities.

Scheme 1. Methods for the preparation of polysubstituted furans from the reaction with ene-yne-ketones.

tested a range of well-known metal photocatalysts, such as iridium- and ruthenium-based in 1,2-dichloroethane. We were pleased to see the formation of desired product 3a in 38% yield with Ir(ppy)3 (entry 5) and in 68% yield with RuCl2(bpy)3 (entry 6). Next, a variety of reaction parameters were assessed. A solvent screening studies indicated that DCE, CH2Cl2, or CH3CN were necessary for good conversion (Entries 6–8), while other organic solvents such as acetone, DMSO, or DMF gave little or almost no conversion to product (Entries 9–11). A significant increase in yield was obtained using Na2CO3 (1.0 equiv) as an additive, affording 3a in 98% yield (Entry 12). Other bases such as Li2CO3, K2CO3, NaOH, KOH, K2HPO4, and NEt3 were less efficient (Entries 13–18). The control experiments in the absence of either photocatalyst or visible light and, as expected, no conversion to the desired product was observed (Entries 19 and 20). These results confirm the essential roles of the photocatalyst and light in the reaction mechanism. Furthermore, shortening the reaction time to 4 h led to a decrease of yield to 63% (entry 21). Thus, the optimized reaction conditions were determined to be the combination of RuCl2(bpy)3 (3.0 mol%), Na2CO3 (1.0 equiv) in DCE solvent at 25 °C for 8 h under 10 W blue LED conditions as shown in entry 12.

Table 1 Optimization of the reaction conditions a O

O

O O

Recently, visible light photoredox catalysis as a greener alternative to traditional radical reactions has led to the development of several useful protocols for important organic transformations.19 In continuation of our interest in the preparation of organofluorine compounds,20 we considered the possibility of using visible-light photoredox catalyzed synthesis of polysubstituted furfuryl trifluoroacetamide derivatives that are valuable synthetic targets. Our approach features a photoirradiation 5-exo-dig cyclization of the enynones to generate the furan-substituted carbene intermediate,21 which undergoes an intermocular trapping process by 2,2,2-trifluoroacetamide to form the target furfuryl trifluoroacetamides (Scheme 1c). 2. Results and Discussion To test the cyclization under different catalysts, the 3-(3phenylprop-2-yn-1-ylidene)pentane-2,4-dione 2a and 2,2,2trifluoroacetamide 1 were chosen as model substrates (Table 1). We started our study by adopting the similar reaction conditions as independently reported by the research groups of Clark (Entry 1),10 López (Entry 2),12 and Xu (Entry 3),22 for the synthesis of substituted furan derivatives. Under these experimental conditions, the cyclization of ene–yne–ketone 2a with 2,2,2-trifluoroacetamide 1 took place to give furfuryl trifluoroacetamide product 3a in 24%, 10%, and 16% yield, respectively (Entries 1-3). Encouraged by this initial result, we decided to evaluate the influence of each reaction parameter, such as catalyst, base, and solvent. Saito and co-workers reported that upon photoirradiation αdiketones conjugated with ene-yne undergo cyclization to generate the bifuran derivatives via the formation of carbene intermediates.21 On the basis of these reports, we envisioned the possibility of synthesizing furfuryl trifluoroacetamide by employing a visible light photoredox catalysis protocol. Indeed, the reaction was performed in the presence of Eosin-Y photocatalyst under visible light irradiation (10 W blue LEDs) failed to give the desired trifluoroacetamide product giving back mostly starting material (entry 4). Our further screening

+ Ph 2a

Entry

Cat.

H2N

Conditions

O O

CF3

CF3 NH

1

Ph

Solvent

Temp (°C)

Base

3a

Time (h)

Yield (%) b

1 THT CH2Cl2 40 24 24 2 ZnCl2 CH2Cl2 25 8 10 3c) Pd2(dba)3 DCE 25 8 16 4d) Eosin-Y DCE 25 8 0 5d) Ir(ppy)3 DCE 25 8 38 6d) RuCl2(bpy)3 DCE 25 8 68 7d) RuCl2(bpy)3 CH2Cl2 25 8 65 8d) RuCl2(bpy)3 CH3CN 25 8 66 9d) RuCl2(bpy)3 Acetone 25 8 45 10d) RuCl2(bpy)3 DMSO 25 8 3 11d) RuCl2(bpy)3 DMF 25 8 8 12d) RuCl2(bpy)3 DCE 25 Na2CO3 8 98 13d) RuCl2(bpy)3 DCE 25 Li2CO3 8 21 14d) RuCl2(bpy)3 DCE 25 K2CO3 8 80 15d) RuCl2(bpy)3 DCE 25 NaOH 8 19 16d) RuCl2(bpy)3 DCE 25 KOH 8 16 17d) RuCl2(bpy)3 DCE 25 K2HPO4 8 53 18d) RuCl2(bpy)3 DCE 25 NEt3 8 11 19d) DCE 25 Na2CO3 8 0 20e) RuCl2(bpy)3 DCE 25 Na2CO3 8 0 21d) RuCl2(bpy)3 DCE 25 Na2CO3 4 63 a Reaction conditions: 1 (0.088 mmol, 1.8 equiv), 2a (0.050 mmol, 1.0 equiv), base (0.050 mmol, 1.0 equiv), catalyst (0.0015 mmol, 3.0 mol%), solvent (1.0 mL), air; THT = tetrahydrothiophene; DCE = 1,2dichloroethane. b The yield was determined by internal standard.

19

F NMR spectroscopy with PhOCF3 as

c

With addition of 4 Å MS.

d

Under 10 W blue LED conditions.

e

Kept in the dark.

a

Table 2 Scope of ene-yne-ketones O R2

+

H2N

R3

2

R1

RuCl2(bpy)3 (3.0 mol%) Na2CO3 (1.0 equiv)

O

R1

CF3

R2 O O

Blue LEDs DCE, r.t., 8 h

1

CF3 NH R3

O

3 R

O O

O CF3

NH

O

O O CF3

O O

NH

CF3

R R R = H, 3a, 98% R = Me, 3b, 61% R = Et, 3c, 56% R = n-Pr, 3d, 57% R = OEt, 3e, 73% R = CF3, 3f, 25%

NH

R R = H, 3g, 82% R = Me, 3h, 49%

R = Me, 3i, 77% R = F, 3j, 89% R = Cl, 3k, 79%

R

O O

RO

O R O O

CF3 NH

CF3

CF3

NH

NH

Ph 3n, 88%

R = Me, 3o, 83% R = Et, 3p, 50% R = t-Bu, 3q, 89%

O

R = Me, 3l, 78% R = Br, 3m, 64%

O

O O CF3

O t-BuO

O O

O O

O

NH EtO

O O

enynones are relatively lower than that of unsubstituted substrate, presumably due to the electron-donating ability of the substituents is unfavored for the formation of active intermediate. The ene-yne-ketone containing the electronwithdrawing substituent such as trifluoromethyl at the paraposition of the phenyl ring was also subjected to the reaction to afford the desired product 3f, albeit which was obtained in 25% yield. Likewise, the reaction proceeds successfully with arylformyl-substituted enynones having different substituents at various positions on the phenyl rings, affording the corresponding products 3g−3m in generally good yields. It should be noted that the reaction tolerates the halo (F, Cl, and Br) substitutions on the aromatic rings (3j, 3k, and 3m), enabling the possibility for further derivatizations through metal-catalyzed cross-coupling. Naphthoyl-substituted enynone reacted smoothly with 1 furnishing the furan product 3n in 88% yield. Similarly, the alkoxylcarbonyl-substituted enynones were also compatible affording the desired products 3o−3y in moderate to excellent yields (50–92%). Even the ester carbonyl-substituted enynone produced the corresponding products 3z in 96% yield. It is noteworthy that the correct regioisomer was confirmed by single-crystal X-ray analysis of compound 3w (Figure 2). Notably, reaction of cyanosubstituted enynones with 1 was also efficient and afforded the desired product 3aa in 81% yield. Moreover, cyclic enynone substrates participated well in the reaction to furnish the corresponding products 3ab and 3ac in 98% and 67% yield, respectively.

CF3 O O

CF3

CF3

NH

NH 3s, 82% R

3r, 88%

3t, 71%

O

O EtO

EtO

O O

O

CF3

CF3 NH

3aa, 81%

NH

3ab, 98%

3z, 96%

O

O O

CF3 NH

R = H, 3w, 92% R = OMe, 3x, 80% R = F, 3y, 86%

O

O O

O

NH

R = H, 3u, 92% R = Me, 3v, 79%

NC

O O

CF3

CF3 NH

R

EtO

O O

O O CF3

Figure 2. ORTEP drawing of 3w. Thermal ellipsoids are drawn at 40% probability.

NH

3ac, 67%

a

Reaction conditions: 1 (0.88 mmol, 1.8 equiv), 2 (0.50 mmol, 1.0 equiv), RuCl2(bpy)3 (0.015 mmol, 3.0 mol%), Na2CO3 (0.50 mmol, 1.0 equiv), DCE (5.0 mL), air, 10 W blue LEDs; Isolated yields.

With the optimized reaction conditions in hand, the scope of ene-yne-ketone was explored and the results are summarized in Table 2. The transformation was applicable to a variety of eneyne-ketones bearing a wide range of substituents. The methyl, ethyl, n-propyl, and ethoxy groups on the phenyl rings at the alkyne terminus underwent reaction to afford the desired products 3b−3e in moderate to good yields. However, the yields of furfuryl trifluoroacetamide products derived from electron-donating substituents on the benzene rings of the

To elucidate the reaction mechanism, the cyclization was carried out to probe for radical intermediates (Scheme 2). When the reaction of 2a with 1 was performed under the standard condition in the presence of radical scavenger such as TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) or BHT (butylated hydroxytoluene), only trace amount of furfuryl trifluoroacetamide product 3a was formed. These results suggest that a free-radical intermediate might be involved in this transformation.

Scheme 2. Mechanistic studies to probe existence of radical intermediates.

4

Tetrahedron

Based on above control experiments and findings from previous studies,21 following plausible reaction pathway has been proposed (Scheme 3). Photoexcitation of enynones would lead to the formation of 1,4-biradicals I, which underwent radical cyclization to furnish furan-substituted carbenes II. Subsequently, trapping of II with 2,2,2-trifluoroacetamide could afford the desired furfuryl trifluoroacetamide product 3.

Acknowledgments Financial support from the National Natural Science Foundation of China (21772022), and Fuzhou University is gratefully acknowledged. Supplementary Material Supplementary data associated with this article can be found, in the online version. References and notes 1.

Scheme 3. Plausible reaction pathway. 3. Conclusions In summary, we have presented a new visible-light photoredox catalyzed reaction of enynones with 2,2,2trifluoroacetamide. It gives access to highly substituted furfuryl trifluoroacetamide derivatives in moderate to excellent yields under mild reaction conditions. This process was proposed to be involved the generation of a furan-substituted carbene intermediate via photoirradiation 5-exo-dig cyclization followed by trapping by 2,2,2-trifluoroacetamide.

2. 3. 4. 5. 6. 7. 8.

4. Experimental 4.1 General experimental 1

H NMR, 19F NMR and 13C NMR spectra were recorded using Bruker AVIII 400 spectrometer. 1H NMR and 13C NMR chemical shifts were reported in parts per million (ppm) downfield from tetramethylsilane and 19F NMR chemical shifts were determined relative to CFCl3 as the external standard and low field is positive. Coupling constants (J) are reported in Hertz (Hz). The residual solvent peak was used as an internal reference: 1H NMR (chloroform δ 7.26) and 13C NMR (chloroform δ 77.0). The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad. Enynones were prepared according to the published procedures.23 Other reagents were received from commercial sources. Solvents were freshly dried and degassed according to the purification handbook Purification of Laboratory Chemicals prior to use. 4.2 General procedure for visible-light photoredox catalyzed synthesis of furfuryl trifluoroacetamides The enynones (2) (0.50 mmol), trifluoroacetamide (1) (100 mg, 0.88 mmol), RuCl2(bpy)3 (9.6 mg, 0.015 mmol, 0.030 equiv), Na2CO3 (53 mg, 0.50 mmol, 1.0 equiv), and 1,2dichloromethane (5.0 mL) were added to a reaction tube equipped with a stir bar. The tube was then exposed to blue LEDs irradiation at room temperature in air with stirring for 8 h. After the reaction was completed, the reaction mixture was extracted with 1,2-dichloromethane (30 mL), and washed with water (30 mL). The organic phase was dried with MgSO4 and evaporated in vacuo after filtration. The resulting residue was purified by column chromatography on silica gel to give the desired products 3.

9.

10.

11. 12. 13. 14. 15. 16.

17.

18.

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Highlights:




A visible-light photoredox catalyzed synthesis of furfuryl trifluoroacetamides was developed. Various furfuryl trifluoroacetamides were obtained in moderate to excellent yields. A wide range of functional groups were tolerated.

Declaration of interests


The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: