Synthesis of Quinone Methide Substituted ... - ACS Publications

Aug 4, 2017 - Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan ... remarkable intrinsic antiproliferative properties, which have key...
3 downloads 0 Views 1MB Size
Research Article pubs.acs.org/journal/ascecg

Synthesis of Quinone Methide Substituted Neonicotinoid Derivatives via 1,6-Conjugate Addition of N‑Benzyl Nitro Ketene Aminals with para-Quinone Methides Accompanying Oxidation Bao-Qu Wang, Qin Luo, Qiang Xiao, Jun Lin,* and Sheng-Jiao Yan* Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. China S Supporting Information *

ABSTRACT: A concise and efficient route for the synthesis of quinone methide substituted neonicotinoid derivatives (4−5) via the one-pot Cs2CO3-catalyzed 1,6-conjugate addition of N-benzyl nitro ketene amines (2) or 1,1-enediamines (3) with paraquinone methides (1) in acetone and an oxidation reaction using atmospheric oxygen has been developed. This protocol represents a route to obtain a novel class of quinone methide substituted neonicotinoid derivatives in a concise, rapid, and practical manner. This reaction is particularly attractive because of the following features: low-cost and biocompatible solvent, mild temperature, atomic economy, high yields, and potential biological activity of the product. KEYWORDS: 1,6-Conjugate addition, Environmentally friendly, Oxidation, Neonicotinoids, para-Quinone methides



methides (p-QMs) are important intermediates in the field of chemistry, medicine, and biological research.11,12 For example, ferrocenyl quinone methides A and B (Figure 1) possess remarkable intrinsic antiproliferative properties, which have key anticancer roles.13−15 According to the splicing principle of the drug’s molecular structure, we tried to combine the two active core structures pictured above in the hope of producing a new class of pharmaceutical molecules which may possess potential bioactivities. As part of our ongoing research effort, we tried to use N-benzyl nitro ketene aminals (NBNKAs, 2) and 1,1enediamines (EDAMs, 3) as synthons to accomplish this goal. NBNKAs belong to heterocyclic ketene aminals (HKAs)16−23 which are widely used to construct molecular diverse heterocyclic compounds24−32 such as spirooxindoles,33,34 quinolones, pyridines,35 pyrroles, and others. However, the structural features of p-QMs result from the assembly of carbonyl and olefin moieties, and they have been widely used in

INTRODUCTION All over the world, over 50% of major chemical production is related to the use of the oxidation reaction, including the oxidation of hydrocarbons and oxygenated chemicals. Among organic reactions, oxidation reactions are the most difficult to control, with accompanying byproducts, which lead to low yields with poor selectivity of desired products. At this time, inorganic oxygen donors, such as sodium hypochlorite, sodium hypobromite, nitric acid, potassium peroxymonosulfate, chromium trioxide, potassium permanganate, and potassium dichromate, etc., are still used to produce oxidation reactions. The use of inorganic electron donors as oxidants generates large amounts of salt as a waste product, which can cause environmental pollution and places a strain on waste resource management. Oxygen, however, is the most environmentally friendly industrial oxidant. The overall structure of neonicotinoid derivatives exhibits special molecular characteristics1 including an electron-withdrawing nitro, a flexible side chain, and guanidine/amidine groups. Neonicotinoid derivatives exhibit a potent insecticidal activity (Figure 1; 6-Cl-PMNI, IPPA08, and Palchongding)2−9 and have strong antimicrobial properties.10 para-Quinone © 2017 American Chemical Society

Received: June 30, 2017 Revised: August 1, 2017 Published: August 4, 2017 8382

DOI: 10.1021/acssuschemeng.7b02166 ACS Sustainable Chem. Eng. 2017, 5, 8382−8389

Research Article

ACS Sustainable Chemistry & Engineering

Figure 1. Biologically active neonicotinoids and para-quinone methide compounds.

Therefore, the discovery of a practical and efficient method for 1,6-conjugate addition and the oxidation reaction by atmospheric O2 in one step is still a highly desirable and yet formidable challenge (Figure 2). The oxidative ability of atmospheric oxygen is usually very poor and often requires a catalyst to increase its oxidative ability. As a result, applicable literature seldom mentions the utilization of oxygen without a catalyst. Herein, we describe 1,6conjugate addition and oxidation by using an oxygen oxidizer for the synthesis of quinone methide substituted neonicotinoid derivatives (also named para-quinone methide derivatives) (4) in a single-step reaction. To the best of our knowledge, the synthesis of these derivatives has not been reported using 1,6conjugate addition followed by the oxidation of para-quinone methide (1) and NBNKAs (2) or EDAMs (3).

a variety of addition reactions as universal Michael receptors, and are also chemically defined as neutral and zwitterionic resonance entities.36,37 These structural features also allow for natural product synthesis as well as for the production of bioactive molecules.38−41 There have been comprehensive reports produced about para-quinone methide reactions such as [3 + 2] addition,42−46 [4 + 2] cycloaddition,47 [1 + 4] addition,48 and others.49−52 Since Fan and Jørgensen reported on the 1,6-addition reaction of methylene quinone compounds,53−60 many catalytic systems such as transition-metal catalysts (Figure 2),61−67 BF3·Et2O (Figure 2),68,69 N-



EXPERIMENTAL SECTION

General Methods. All compounds were fully characterized by spectroscopic data. The NMR spectra were recorded on a Bruker DRX500 and DRX600 device. Chemical shift (δ) values are expressed in ppm, J values are given in Hz, and deuterated DMSO-d6 and CDCl3 were used as the solvent. IR spectra were recorded on an FT-IR Thermo Nicolet Avatar 360 device using a KBr pellet. The reactions were monitored by thin layer chromatography (TLC) using silica gel GF254. The melting points were determined on an XT-4A melting point apparatus and are uncorrected. HRMS was performed on an Agilent LC/Msd TOF instrument. Materials used were purchased from Adamas-beta Corp., Ltd. All chemicals and solvents were used as received without further purification unless otherwise noted. Column chromatography was performed on silica gel (200−300 mesh). 4-Benzylidene-2,6-di-tertbutylcyclohexa-2,5-dienone 1 was prepared according to the literature,80,81 and NBNKAs 2 were also prepared in this way;82,83 EDAMs 3 were prepared according to the literature.84 General Procedure for the Synthesis of Compounds 4−5. A 25 mL sealed tube was charged with p-QMs 1 (1.1 mmol), acetone (15 mL), and NBNKAs 2 (1.0 mmol) or EDAMs 3 (1.0 mmol). A small amount of Cs2CO3 (10 mg) was then added to this mixture. The solution was stirred for 8 h at 70 °C. The mixture was cooled to room temperature and added to 40 mL of water, then neutralized with saturated NH4Cl solution to alkalinity, after which time it was extracted with an appropriate amount of ethyl acetate. Its organic phase was combined and dried over anhydrous Na2SO4 and then concentrated under reduced pressure and purified by fast column chromatography (petroleum ether/EtOAc = 1/1). This produced a yield of 4−5 of 70−92%.

Figure 2. Strategies for 1,6-conjugate addition and oxidation of pQMs.

heterocyclic carbene catalysts (Figure 2),70,71 K2CO3 (Figure 2),72,73 phosphoric acids (Figure 2),74,75 and other catalysts were reportedly used in the 1,6-addition reaction.76,77 Recently, the Li Xin group realized the organocatalyzed asymmetric 1,6conjugate addition of para-quinone methides with dicyanoolefins.78,79 To our knowledge, all of the above reactions produced the phenolic compounds via the 1,6-addition reactions of pQMs with different nucleophilic reagents. However, the method of p-QM derivative synthesis with a large conjugated ketene which is based on the 1,6-addition and the oxidation of p-QMs with nucleophilic reagents has not been realized. 8383

DOI: 10.1021/acssuschemeng.7b02166 ACS Sustainable Chem. Eng. 2017, 5, 8382−8389

Research Article

ACS Sustainable Chemistry & Engineering Table 1. Optimization of the Reaction Conditionsa

entry

solvent

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane THF CH2Cl2 EtOH toluene DMF DMSO ethyl acetate CH3CN CH3COCH3 CH3COCH3 CH3COCH3 CH3COCH3 CH3COCH3

catalyst

T (°C)

t (h)

yieldb (%)

Et3Nd K2CO3d NaHCO3d Cs2CO3d piperidined t-BuOKd Cs2CO3d Cs2CO3d Cs2CO3d Cs2CO3d Cs2CO3d Cs2CO3d Cs2CO3d Cs2CO3d Cs2CO3d Cs2CO3d Cs2CO3d Cs2CO3d Cs2CO3e

room temp reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux reflux 70 °C 70 °C 70 °C 70 °C 70 °C

8 8 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 8 10 8 8

nrc nr nr nr nr 40 nr nr nr nr nr nr 20 30 40 75 80 90 90 92 90

a Reactions (entries 1−21) were carried out using 1c (1.1 mmol), 2c (1.0 mmol), and solvent (15 mL). bIsolated yield based on NBNKA 2c. cnr = not recorded. dCatalyst (0.05 mmol). eCatalyst (0.1 mmol).



RESULTS AND DISCUSSION In this paper, we attempted to establish a one-pot protocol to synthesize a series of quinone methide substituted neonicotinoid derivatives. To obtain optimal reaction conditions for the synthesis of our target molecule, we chose the reaction of pQMs (1c) with NBNKAs (2c) as a model. First, the reaction of 1c with 2c was carried out with a different catalyst, consisting of Et3N, K2CO3, NaHCO3, Cs2CO3, piperidine, and t-BuOK at different temperatures (Table 1, entries 1−8). The results showed a product yield of 45% (Table 1, entry 6) with the Cs2CO3 catalyst for 4 h in 1,4-dioxane. Next, we investigated the effects of several solvents, including THF, CH2Cl2, EtOH, CH3COCH3, toluene, DMF, DMSO, ethyl acetate, and CH3CN at reflux temperatures (Table 1, entries 9−17). With most solvents, the target compound was not produced at all (Table 1, entries 9−12); however, with DMF and DMSO the products were obtained, but only at a low yield (Table 1, entries 13 and 14). However, when the solvents ethyl acetate, CH3CN, and CH3COCH3 were used, an excellent yield of the desired compound 4cc was obtained, with the solvent CH3COCH3 producing an optimal yield (Table 1, entries 15−17); additionally, with the reaction time extended to 8 h, the yield of a desirable product 4cc was improved to 92%. However, when the reaction time was increased to 10 h, the yield of a desirable product was not improved (Table 1, entries 18 and 19). On this basis, we further examined the effects of the

amount of catalyst upon percent yield. When we adjusted the amount of catalyst Cs2CO3 to 5% (0.05 mmol) of the amount of raw material 2c, the target compound 4cc was obtained at a 92% yield. The yield was 90% when the amount of Cs2CO3 was adjusted to 10% (0.1 mmol) of the amount of raw material 2c (Table 1, entries 20 versus 21). Thus, the use of catalyst at 5% by weight sufficiently produces high yield percentages. Preparation of 4cc required a mixture of 1c and 2c in acetone for about 20 min, along with the addition of Cs2CO3 at 70 °C. Under optimal conditions, we explored the scope and limitations of these addition reactions involving various p-QMs (1a−1e) with NBNKAs (2a−2h) or EDAMs (3a−3f) (Table 2, entries 1−41). The results showed that although the reaction proceeded within 8 h in all cases (Table 2, entries 1−30), the different substituent groups (R = F, Cl, H, Me, or MeO) at the C8 position of the p-QMs 1 usually had a slight influence on the yields. An electron-withdrawing group on p-QMs 1 (F or Cl) usually can obtain higher yields than an electron-donating group on p-QMs 1 (Me or MeO) (Table 2, entries 1−11 versus 20−30). In general, an electron-withdrawing group (F or Cl) on NBNKAs 2 had higher yields than an electron-donating group (Me or MeO) on NBNKAs 2 (Table 2, entries 1 versus 2, 7 versus 8−9, and 20 versus 21 and 22). For the acquisition of molecular diversity of the products, 1,1-enediamines (3), which have a different structure, were used as a substrate reacted with p-QMs 1 to synthesize the products 5 with good yields (78−88%). In cases where the 8384

DOI: 10.1021/acssuschemeng.7b02166 ACS Sustainable Chem. Eng. 2017, 5, 8382−8389

Research Article

ACS Sustainable Chemistry & Engineering Table 2. One-Pot Protocol for the Regioselective Synthesis of Compounds 4−5a

entry

1 (R)

2 (Ar) or 3 (R′)

4 or 5

yieldb (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41

1a (F) 1a (F) 1a (F) 1a (F) 1a (F) 1b (Cl) 1b (Cl) 1b (Cl) 1b (Cl) 1b (Cl) 1b (Cl) 1c (H) 1c (H) 1c (H) 1c (H) 1c (H) 1c (H) 1c (H) 1c (H) 1d (Me) 1d (Me) 1d (Me) 1d (Me) 1e (MeO) 1e (MeO) 1e (MeO) 1e (MeO) 1e (MeO) 1e (MeO) 1e (MeO) 1b (Cl) 1b (Cl) 1b (Cl) 1b (Cl) 1c (H) 1c (H) 1c (H) 1c (H) 1c (H) 1d (Me) 1d (Me)

2b (4-FC6H4) 2d (4-CH3C6H4) 2e (4-CH3OC6H4) 2f (2,4-difluorophenyl) 2g (3,4-dichlorophenyl) 2a (3-FC6H5) 2b (4-FC6H4) 2d (4-CH3C6H4) 2e (4-CH3OC6H4) 2f (2,4-difluorophenyl) 2g (3,4-dichlorophenyl) 2a (3-FC6H5) 2b (4-FC6H4) 2c (C6H5) 2d (4-CH3C6H4) 2e (4-CH3OC6H4) 2f (2,4-difluorophenyl) 2h (3,5-difluorophenyl) 2g (3,4-dichlorophenyl) 2b (4-FC6H4) 2d (4-CH3C6H4) 2e (4-CH3OC6H4) 2g (3,4-dichlorophenyl) 2a (3-FC6H4) 2b (4-FC6H4) 2d (4-CH3C6H4) 2e (4-CH3OC6H4) 2f (2,4-difluorophenyl) 2h (3,5-difluorophenyl) 2g (3,4-dichlorophenyl) 3a (4-FC6H4CH2) 3b (4-ClC6H4CH2) 3c (C6H5CH2CH2) 3d (4-CH3OC6H4CH2CH2) 2e (4-FC6H4) 3a (4-FC6H4CH2) 3b (4-ClC6H4CH2) 3c (C6H5CH2CH2) 3d (4-CH3OC6H4CH2CH2) 3a (4-FC6H4CH2) 3f (4-CH3C6H4CH2)

4ab 4ad 4ae 4af 4ag 4ba 4bb 4bd 4be 4bf 4bg 4ca 4cb 4cc 4cd 4ce 4cf 4ch 4cg 4db 4dd 4de 4dg 4ea 4eb 4ed 4ee 4ef 4eh 4eg 5ba 5bb 5bc 5bd 5ce 5ca 5cb 5cc 5cd 5da 5df

90 80 91 85 85 80 89 75 80 88 80 80 85 92 85 80 90 89 85 75 70 71 75 80 85 87 86 80 82 90 80 83 79 84 86 81 83 78 88 82 85

a

All reactions were run under the following conditions: 1 (1.1 mmol) and 2 (1.0 mmol) were refluxed in the solvent acetone (15 mL) for 20 min, and then Cs2CO3 was added to reflux 8 h at 70 °C. bIsolated yield based on NBNKAs 2 or EDAMs 3.

unequivocally confirmed by X-ray diffraction analysis as shown in Figures 3 (CCDC1558265) and 4 (CCDC1565720). It should be pointed out that the target compound 4af is Econfiguration based on the intramolecular H-bond of 4af. Compound 4af only has one H proton (Figure 3). However, compound 5ce is Z-configuration due to the fact that there is one intramolecular H-bond between the nitro group and 4FC6H4NH of 5ce (Figure 4).

reaction proceeded for 8 h, there were no large discrepancies in product yields for the different substituent groups on 1,1enediamines (3) (Table 2, entries 31−41). The chemical structures of all target derivatives 4−5 were fully characterized by IR, 1H NMR, 13C NMR, and HRMS. For further verification of the structure of the targeted products, one of the representative compounds (4af and 5ce) was selected as a representative compound, whose presence was 8385

DOI: 10.1021/acssuschemeng.7b02166 ACS Sustainable Chem. Eng. 2017, 5, 8382−8389

Research Article

ACS Sustainable Chemistry & Engineering

for 70 °C, promoted by Cs2CO3 only for 3 h, and then with the reaction mixture injected in the HPLC−HRMS system. The molecular ion peak appeared in high-resolution mass spectrometry [HRMS (TOF ES + ): m/z calcd for C33H40Cl2N3O4 [M + H]+, 612.2390; found, 612.2329] (see the Supporting Information, which contains the HRMS spectra of compound Int 2). However, the pure compound of Int 2 could not be isolated by silica gel column chromatography under a nitrogen atmosphere. Therefore, we speculated that Int 2 had been oxidized by oxygen when we concentrated the reaction mixture.



CONCLUSIONS In summary, we looked at the use of the Cs2CO3 catalyst for the efficient synthesis of neonicotinoid quinone methide derivatives by a 1,6-coupling reaction along with the oxidation of para-quinone methides 1 with NBNKAs 2 or EDAMs 3 in acetone. Novel classes of neonicotinoid quinone methide derivatives produce adequate to excellent yields. The reaction itself may be performed easily under mild conditions with very good atomic economy and operational simplicity. Moreover, this series of neonicotinoid quinone methide derivatives may possess potential biological and pharmaceutical activities. Our further investigations will aim at assessing the in vitro biological activities of compounds 4−5.

Figure 3. X-ray crystal structures containing the intramolecular Hbonds of 4af; ellipsoids are drawn at the 30% probability level.



Figure 4. X-ray crystal structures containing the intramolecular Hbonds of 5ce; ellipsoids are drawn at the 30% probability level.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssuschemeng.7b02166. Spectroscopic and analytical data as well as the original copy of 1H and 13C NMR spectra of all new compounds (PDF) X-ray crystallographic data of compounds 4af (CCDC 1558265) and 5ce (CCDC 1565720) (CIF)

A proposed mechanism for the synthesis of the quinone methide substituted neonicotinoid derivatives 4 by the 1,6conjugate addition of p-QMs 1 with NBNKAs 2 and oxidation using oxygen is illustrated in Scheme 1. NBNKAs 2, with a strong electron-withdrawing nitro group at the α-position and two electron-donating diamino groups on the diaza-heterocycle of NBNKAs,85,86 might serve as the nucleophilic component and may also produce 1,6-conjugate addition to the olefin bond group of p-QMs 1 to form intermediate Int 1. The Int 1 was followed by imine-enamine tautomerization to produce Int 2. Finally, the oxidation of Int 2 by oxygen is used to form the target compound 4. To prove this mechanism, we tried to perform the reaction under a nitrogen atmosphere in acetone



AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected].

Scheme 1. Mechanism Hypotheses for the Synthesis of Target Compounds 4

8386

DOI: 10.1021/acssuschemeng.7b02166 ACS Sustainable Chem. Eng. 2017, 5, 8382−8389

Research Article

ACS Sustainable Chemistry & Engineering *E-mail: [email protected]. Phone/Fax: +86 87165031633.

Strong Antiproliferative Agents: Formation by Metabolic and Chemical Oxidation of Ferrocenyl Phenols. Angew. Chem., Int. Ed. 2009, 48, 9124−9126. (14) Wang, Y.; Pigeon, P.; Top, S.; McGlinchey, M. J.; Jaouen, G. Organometallic Antitumor Compounds: Ferrocifens as Precursors to Quinone Methides. Angew. Chem., Int. Ed. 2015, 54, 10230−10233. (15) Wang, Y.; Richard, M.-A.; Top, S.; Dansette, P. M.; Pigeon, P.; VessiÀ res, A.; Mansuy, D.; Jaouen, G. Ferrocenyl Quinone Methide− Thiol Adducts as New Antiproliferative Agents: Synthesis, Metabolic Formation from Ferrociphenols, and Oxidative Transformation. Angew. Chem., Int. Ed. 2016, 55, 10431−10434. (16) Bao, H.; Shao, X.; Zhang, Y.; Deng, Y.; Xu, X.; Liu, Z.; Li, Z. Specific Synergist for Neonicotinoid Insecticides: IPPA08, a cisNeonicotinoid Compound with a Unique Oxabridged Substructure. J. Agric. Food Chem. 2016, 64, 5148−5155. (17) Huang, Z.-T.; Wang, M.-X. Heterocyclic ketene aminals. Heterocycles 1994, 37, 1233−1262. (18) Viswanathan, N. I.; Balakrishnan, V. 4-Nitro-1,2,3-triazoles from nitro-α,β-unsaturated gem-diamines. J. Chem. Soc., Perkin Trans. 1 1979, 1, 2361−2363. (19) Huang, Z.; Wang, M. The reaction of benzoyl substituted heterocyclic ketene aminals with 4-nitrobenzhydroximic acid chloride. Synth. Commun. 1991, 21, 1167−1176. (20) Ma, Y.-L.; Wang, K.-M.; Lin, X.-R.; Yan, S.-J.; Lin, J. Threecomponent cascade reaction synthesis of polycyclic 1,4-dihydropyridine derivatives in water. Tetrahedron 2014, 70, 6578−6584. (21) Chen, N.; Meng, X.; Zhu, F.; Cheng, J.; Shao, X.; Li, Z. Tetrahydroindeno[1′,2′:4,5]-pyrrolo[1,2-a]imidazol-5(1H)-ones as Novel Neonicotinoid Insecticides: Reaction Selectivity and Substituent Effects on the Activity Level. J. Agric. Food Chem. 2015, 63, 1360− 1369. (22) Chen, X.-B.; Liu, Z.-C.; Lin, X.-R.; Huang, R.; Yan, S.-J.; Lin, J. Highly Diastereoselective Convergent Synthesis of Polycyclic Pyrroles with Consecutive Quaternary Stereocenters: Cascade Construction of Multiple C-C and C-Hetero Bonds. ACS Sustainable Chem. Eng. 2014, 2, 2391−2398. (23) Chen, X.-B.; Liu, Z.-C.; Yang, L.-F.; Yan, S.-J.; Lin, J. A ThreeComponent Catalyst-Free Approach to Regioselective Synthesis of Dual Highly Functionalized Fused Pyrrole Derivatives in WaterEthanol Media: Thermodynamics versus Kinetics. ACS Sustainable Chem. Eng. 2014, 2, 1155−1163. (24) Yu, F.; Huang, R.; Ni, H.; Fan, J.; Yan, S.; Lin, J. Threecomponent stereoselective synthesis of spirooxindole derivatives. Green Chem. 2013, 15, 453−462. (25) Chen, X.-B.; Liu, X.-M.; Huang, R.; Yan, S.-J.; Lin, J. ThreeComponent Synthesis of Indanone-Fused Spirooxindole Derivatives. Eur. J. Org. Chem. 2013, 2013, 4607−4613. (26) Zhou, B.; Liu, Z.-C.; Qu, W.-W.; Yang, R.; Lin, X.-R.; Yan, S.-J.; Lin, J. An environmentally benign, mild, and catalyst-free reaction of quinones with heterocyclic ketene aminals in ethanol: site-selective synthesis of rarely fused [1,2-a]indolone derivatives via an unexpected anti-Nenitzescu strategy. Green Chem. 2014, 16, 4359−4370. (27) Yu, F.-C.; Hao, X.-P.; Lin, X.-R.; Yan, S.-J.; Lin, J. Synthesis of fused polyhalogeno-7a-hydroxy-[1,2-a]indol-5-one derivatives. Tetrahedron 2015, 71, 4084−4089. (28) Yan, S.-J.; Liu, Y.-J.; Chen, Y.-L.; Liu, L.; Lin, J. An efficient onepot synthesis of heterocycle-fused 1,2,3-triazole derivatives as anticancer agents. Bioorg. Med. Chem. Lett. 2010, 20, 5225−5228. (29) Li, M.; Zhou, Z.-M.; Wen, L.-R.; Qiu, Z.-X. Chemistry of Heterocyclic Ketene Aminals: Construction of Imidazo(pyrido)[1,2a]pyridines and Imidazo(pyrido)[3,2,1-ij][1,8]naphthayr-idines via DABCO-Catalyzed Tandem Annulations. J. Org. Chem. 2011, 76, 3054−3063. (30) Zhang, Y.-C.; Liu, Z.-C.; Yang, R.; Zhang, J.-H.; Yan, S.-J.; Lin, J. Regioselective construction of 1,3-diazaheterocycle fused [1,2-a][1,8]naphthyridine derivatives via cascade reaction of quinolines with heterocyclic ketene aminals: a joint experimental-computational approach. Org. Biomol. Chem. 2013, 11, 7276−7288.

ORCID

Jun Lin: 0000-0002-2087-6013 Sheng-Jiao Yan: 0000-0002-7430-4096 Notes

The authors declare no competing financial interest.



ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (21662042, 21362042, U1202221, and 21262042), the Program for Changjiang Scholars and Innovative Research Team in University (IRT17R94), the Natural Science Foundation of Yunnan Province (2017FA003), the Reserve Talent Foundation of Yunnan Province for Middleaged and Young Academic and Technical Leaders (2012HB001), Donglu Schloars of Yunnan University, Excellent Young Talents, Yunnan University, and High-Level Talents Introduction Plan of Yunnan Province.



REFERENCES

(1) Huang, Z.; Liu, Z. Synthesis of benzoyl substituted heterocyclic ketene aminals by condensation of benzoyl ketene mercaptals with diamines. Synth. Commun. 1989, 19, 943−58. (2) Jeschke, P.; Nauen, R. Neonicotinoids- from zero to hero in insecticide chemistry. Pest Manage. Sci. 2008, 64, 1084−1098. (3) Lu, T.-Q.; Mao, S.-Y.; Sun, S.-L.; Yang, W.-L.; Ge, F.; Dai, Y.-J. Regulation of Hydroxylation and Nitroreduction Pathways during Metabolism of the Neonicotinoid Insecticide Imidacloprid by Pseudomonas putida. J. Agric. Food Chem. 2016, 64, 4866−4875. (4) Wang, C.-J.; Wang, G.; Wang, X.-Y.; Liu, M.; Chuai, M.; Lee, K. K. H.; He, X.-S.; Lu, D.-X.; Yang, X. Imidacloprid Exposure Suppresses Neural Crest Cells Generation during Early Chick Embryo Development. J. Agric. Food Chem. 2016, 64, 4705−4715. (5) Matsuda, K.; Buckingham, S. D.; Kleier, D.; Rauh, J. J.; Grauso, M.; Sattelle, D. B. Neonicotinoids: insecticides acting on insect nicotinic acetylcholine receptors. Trends Pharmacol. Sci. 2001, 22, 573−580. (6) Li, J.; Zhang, S.; Wu, C.; Li, C.; Wang, H.; Wang, W.; Li, Z.; Ye, Q. Stereoselective Degradation and Transformation Products of a Novel Chiral Insecticide, Paichongding, in Flooded Paddy Soil. J. Agric. Food Chem. 2016, 64, 7423−7430. (7) Wang, J.; Chen, J.; Zhu, W.; Ma, J.; Rong, Y.; Cai, Z. Isolation of the Novel Chiral Insecticide Paichongding (IPP) Degrading Strains and Biodegradation Pathways of RR/SS-IPP and SR/RS-IPP in an Aqueous System. J. Agric. Food Chem. 2016, 64, 7431−7437. (8) Bai, D.; Lummis, S. C. R.; Leicht, W.; Breer, H.; Sattelle, D. B. Actions of imidacloprid and a related nitromethylene on cholinergic receptors of an identified insect motor neurone. Pestic. Sci. 1991, 33, 197−204. (9) Chen, L.; Huang, R.; Du, X.-X.; Yan, S.-J.; Lin, J. One-Pot Synthesis of Highly Functionalized Bicyclic Imidazopyridinium Derivatives in Ethanol. ACS Sustainable Chem. Eng. 2017, 5, 1899− 1905. (10) He, Y.; Hu, D.; Lv, M.; Jin, L.; Wu, J.; Zeng, S.; Yang, S.; Song, B. Synthesis, insecticidal and antibacterial activities of novel neonicotinoid analogs with dihydropyridine. Chem. Cent. J. 2013, 7, 76. (11) Hamels, D.; Dansette, P. M.; Hillard, E. A.; Top, S.; Vessières, A.; Herson, P.; Jaouen, G.; Mansuy, D. Ferrocenyl Quinone Methides as Strong Antiproliferative Agents: Formation by Metabolic and Chemical Oxidation of Ferrocenyl Phenols. Angew. Chem., Int. Ed. 2009, 48, 9124−9126. (12) Peter, M. G. Chemical Modifications of Biopolymers by Quinones and Quinone Methides. Angew. Chem., Int. Ed. Engl. 1989, 28, 555−570. (13) Hamels, D.; Dansette, P. M.; Hillard, E. A.; Top, S.; Vessires, A.; Herson, P.; Jaouen, G.; Mansuy, D. Ferrocenyl Quinone Methides as 8387

DOI: 10.1021/acssuschemeng.7b02166 ACS Sustainable Chem. Eng. 2017, 5, 8382−8389

Research Article

ACS Sustainable Chemistry & Engineering

(49) Motyakin, M. V.; Wasserman, A. M.; Stott, P. E.; Zaikov, G. E. Possible mediators of the “living” radical polymerization. Spectrochim. Acta, Part A 2006, 63, 802−815. (50) Neilson, A. R.; Morrison, C. F. Peroxy Radical Activated Addition of tert-Butylcatechol to 2,6-Di-tert-butyl-7-Substituted Quinone Methide Polymerization Retarders. Org. Process Res. Dev. 2012, 16, 65−69. (51) Jadhav, A. S.; Anand, R. V. 1,6-Conjugate addition of zinc alkyls to para-quinonemethides in a continuous-flow microreactor. Org. Biomol. Chem. 2017, 15, 56−60. (52) Zhang, X.-Z.; Deng, Y.-H.; Gan, K.-J.; Yan, X.; Yu, K.-Y.; Wang, F.-X.; Fan, C.-A. Tandem Spirocyclopropanation/Rearrangement Reaction of Vinyl p-Quinone Methides with Sulfonium Salts: Synthesis of Spirocyclopentenylp-Dienones. Org. Lett. 2017, 19, 1752−1755. (53) Caruana, L.; Kniep, F.; Johansen, T. K.; Poulsen, P. H.; Jorgensen, K. A. A New Organocatalytic Concept for Asymmetric αAlkylation of Aldehydes. J. Am. Chem. Soc. 2014, 136, 15929−15932. (54) Ramanjaneyulu, B. T.; Mahesh, S.; Anand, R. V. Bis(amino)cyclo-propenylidene-Catalyzed 1,6-Conjugate Addition of Aromatic Aldehydes to para-Quinone Methides: Expedient Access to α,α′Diarylated Ketones. Org. Lett. 2015, 17, 3952−3955. (55) Gai, K.; Fang, X.-X.; Li, X.-Y.; Xu, J.-Y.; Wu, X.-M.; Lin, A.-J.; Yao, H.-Q. Synthesis of spiro[2.5]octa-4,7-dien-6-one with consecutive quaternary centers via 1,6-conjugate addition induced dearomatization of para-quinonemethides. Chem. Commun. 2015, 51, 15831−15834. (56) Jarava-Barrera, C.; Parra, A.; López, A.; Cruz-Acosta, F.; Collado-Sanz, D.; Cardenas, D. J.; Tortosa, M. Copper-Catalyzed Borylative Aromatization of p-Quinone Methides: Enantio-selective Synthesis of DibenzylicBoronates. ACS Catal. 2016, 6, 442−446. (57) Ma, C.; Huang, Y.; Zhao, Y. Stereoselective 1,6-Conjugate Addition/Annulation of para-Quinone Methides with Vinyl Epoxides/ Cyclopropanes. ACS Catal. 2016, 6, 6408−6412. (58) Li, X.; Xu, X.-Y.; Wei, W.-W.; Lin, A.-J.; Yao, H.-Q. Organocatalyzed Asymmetric 1,6-Conjugate Addition of para-Quinone Methides with Dicyanoolefins. Org. Lett. 2016, 18, 428−431. (59) Molleti, N.; Kang, J. Y. Synthesis of DiarylDiazaphosphonates via 1,6-Hydrophosphonyl-ation of p-Quinone Methides with NHeterocyclic Phosphine-Thioureas. Org. Lett. 2017, 19, 958−961. (60) Deng, Y.-H.; Zhang, X.-Z.; Yu, K.-Y.; Yan, X.; Du, J.-Y.; Huang, H.; Fan, C.-A. Bifunctional tertiary amine-squaramide catalyzed asymmetric catalytic 1,6-conjugate addition/aromatization of paraquinonemethides with oxindoles. Chem. Commun. 2016, 52, 4183− 4186. (61) Reddy, V.; Anand, R. V. Expedient Access to Unsymmetrical Diarylindolyl-methanesthrough Palladium-Catalyzed Domino Electrophilic Cyclization-Extended Conjugate Addition Approach. Org. Lett. 2015, 17, 3390−3393. (62) Yuan, Z.-B.; Wei, W.-W.; Lin, A.-J.; Yao, H.-Q. Bifunctional Organo/Metal Cooperatively Catalyzed [3 + 2] Annulation of paraQuinone Methides with Vinylcyclopropanes: Approach to Spiro[4.5]deca-6,9-diene-8-ones. Org. Lett. 2016, 18, 3370−3373. (63) López, A.; Parra, A.; Jarava-Barrera, C.; Tortosa, M. Coppercatalyzed silylation of p-quinonemethides: new entry to dibenzylicsilanes. Chem. Commun. 2015, 51, 17684−17687. (64) Lou, Y.-Z.; Cao, P.; Jia, T.; Zhang, Y.-L.; Wang, M.; Liao, J. Copper-Catalyzed Enantioselective 1,6-Boration of para-Quinone Methides and Efficient Transformation of gem-DiarylmethineBoronates to Triarylmethanes. Angew. Chem., Int. Ed. 2015, 54, 12134− 12138. (65) Ke, M.; Song, Q. Copper-Catalyzed 1,6-Hydrodifluoroacetylation of para-Quinone Methides at Ambient Temperature with Bis(pinacolato)diboron as Reductant. Adv. Synth. Catal. 2017, 359, 384−389. (66) Shen, Y.-Y.; Qi, J.-F.; Mao, Z.-J.; Cui, S.-L. Fe-Catalyzed Hydroalkylation of Olefins with para-Quinone Methides. Org. Lett. 2016, 18, 2722−2725. (67) Yang, C.; Gao, S.; Yao, H.-Q.; Lin, A.-J. Rhodium-Catalyzed Hydroacylation of para-Quinone Methides with Salicylaldehydes: An

(31) Li, M.; Shao, P.; Wang, S.-W.; Kong, W.; Wen, L.-R. FourComponent Cascade Heteroannulation of Heterocyclic Ketene Aminals: Synthesis of Functionalized Tetrahydro-imidazo[1,2-a]pyridine Derivatives. J. Org. Chem. 2012, 77, 8956−8967. (32) Wen, L.-R.; Sun, Q.-C.; Zhang, H.-L.; Li, M. A new rapid multicomponent domino heteroannulation of heterocyclic ketene aminals: solvent-free regioselective synthesis of functionalized benzo[g]imidazo[1,2-a]quinolinediones. Org. Biomol. Chem. 2013, 11, 781− 786. (33) Chen, N.; Zou, M.; Tian, X.; Zhu, F.; Jiang, D.; Cheng, J.; Shao, X.; Li, Z. Isomerization of Ninhydrin-Heterocyclic Ketene Aminal Adducts: Kinetic versus Thermodynamic Control, Solvent Dependency and Mechanism. Eur. J. Org. Chem. 2014, 2014, 6210−6218. (34) Lu, S.; Shao, X.; Li, Z.; Xu, Z.; Zhao, S.; Wu, Y.; Xu, X. Design, Synthesis, and Particular Biological Behaviors of Chain-Opening Nitromethylene Neonicotinoids with Cis Configuration. J. Agric. Food Chem. 2012, 60, 322−330. (35) Yaqub, M.; Arif, N.; Perveen, R.; Batool, J.; Riaz, M. T.; Yaseen, M. One-pot three component cascade synthesis of fused ring quinazoline-2,4-dione derivatives employing heterocyclic ketene aminals as a versatile synthon. Asian J. Chem. 2015, 27, 1013−1018. (36) Parra, A.; Tortosa, M. para-Quinone Methide: a New Player in Asymmetric Catalysis. ChemCatChem 2015, 7, 1524−1526. (37) Nigst, T. A.; Ammer, J.; Mayr, H. AmbidentReactivities of Methylhydrazines. Angew. Chem., Int. Ed. 2012, 51, 1353−1356. (38) Takao, K.-I.; Sasaki, T.; Kozaki, T.; Yanagisawa, Y.; Tadano, K.I.; Kawashima, A.; Shinonaga, H. Syntheses and absolute stereochemistries of UPA0043 and UPA0044, cytotoxic antibiotics having a p-quinone-methide structure. Org. Lett. 2001, 3, 4291−4294. (39) Jansen, R.; Gerth, K.; Steinmetz, H.; Reinecke, S.; Kessler, W.; Kirschning, A.; Müller, R. Elansolid A3, a Unique p-Quinone Methide Antibiotic from Chitinophagasancti. Chem. - Eur. J. 2011, 17, 7739− 7744. (40) Yuan, Y.; Men, H.; Lee, C. Total Synthesis of Kendomycin: A Macro-C-Glycosidation Approach. J. Am. Chem. Soc. 2004, 126, 14720−14721. (41) Smith, A. B.; Mesaros, E. F.; Meyer, E. A. Evolution of a Total Synthesis of (−)-Kendomycin Exploiting a Petasis-Ferrier Rearrangement/Ring-Closing Olefin Metathesis Strategy. J. Am. Chem. Soc. 2006, 128, 5292−5299. (42) Zhang, X.-Z.; Du, J.-Y.; Deng, Y.-H.; Chu, W.-D.; Yan, X.; Yu, K.-Y.; Fan, C.-A. Spirocyclopropanation Reaction of para-Quinone Methides with Sulfonium Salts: The Synthesis of Spirocyclopropanyl para-Dienones. J. Org. Chem. 2016, 81, 2598−2606. (43) Li, S.-H.; Liu, Y.-Y.; Huang, B.; Zhou, T.; Tao, H.-M.; Xiao, Y.J.; Liu, L.; Zhang, J.-L. Phosphine-Catalyzed Asymmetric Intermolecular Cross-VinylogousRauhut-Currier Reactions of Vinyl Ketones with para-Quinone Methides. ACS Catal. 2017, 7, 2805−2809. (44) Zhao, K.; Zhi, Y.; Wang, A.; Enders, D. Asymmetric Organocatalytic Synthesis of 3-Diarylmethine-Substituted Oxindoles Bearing a Quaternary Stereocenter via 1,6-Conjugate Addition to paraQuinone Methides. ACS Catal. 2016, 6, 657−660. (45) Zhang, X.-Z.; Deng, Y.-H.; Yan, X.; Yu, K.-Y.; Wang, F.-X.; Ma, X.-Y.; Fan, C.-A. Diastereoselective and Enantioselective Synthesis of Unsymmetric β,β-Diaryl-α-Amino Acid Esters via Organocatalytic 1,6Conjugate Addition of para-Quinone Methides. J. Org. Chem. 2016, 81, 5655−5662. (46) Angle, S. R.; Arnaiz, D. O. Synthesis of dihydro-1H-indenes via a formal 3 + 2 cycloaddition of Para-Quinonemethidesandstyrenes. J. Org. Chem. 1990, 55, 3708−3710. (47) Zhao, K.; Zhi, Y.; Shu, T.; Valkonen, A.; Rissanen, K.; Enders, D. Organocatalytic Domino Oxa-Michael/1,6-Addition Reactions: Asymmetric Synthesis of Chromans Bearing Oxindole Scaffolds. Angew. Chem., Int. Ed. 2016, 55, 12104−12108. (48) Amoah, E.; Dieter, R. K. Regioselective 1,4-Conjugate Addition of Grignard Reagents to α,β-γ,δ-Dienones and α,β−γ,δ-Dienyl Thiol Esters. J. Org. Chem. 2017, 82, 2870−2888. 8388

DOI: 10.1021/acssuschemeng.7b02166 ACS Sustainable Chem. Eng. 2017, 5, 8382−8389

Research Article

ACS Sustainable Chemistry & Engineering Approach to α,α-Diaryl-2-Hydroxy Acetophenones. J. Org. Chem. 2016, 81, 11956−11964. (68) Gao, S.; Xu, X.-Y.; Yuan, Z.-B.; Zhou, H.-P.; Yao, H.-Q.; Lin, A. J. 6-Addition Arylation of para-QuinoneMethides: An Approach to Unsymmetrical Triarylmethanes. Eur. J. Org. Chem. 2016, 385, 3006− 3012. (69) Lin, C.; Shen, Y.-Y.; Huang, B.; Liu, Y.; Cui, S.-L. Synthesis of Amides and Nitriles from Vinyl Azides and p-Quinone Methides. J. Org. Chem. 2017, 82, 3950−3956. (70) Arde, P.; Anand, R. V. N-Heterocyclic carbene catalysed1,6hydrophosphonylation of p-quinonemethides and fuchsones: an atom economical route to unsymmetrical diaryl- and triarylmethyl phosphonates. Org. Biomol. Chem. 2016, 14, 5550−5554. (71) Goswami, P. W.; Singh, G.; Anand, R. V. N-Heterocyclic Carbene Catalyzed 1,6-Conjugate Addition of Me3Si-CN to paraQuinone Methides and Fuchsones: Access to α-Arylated Nitriles. Org. Lett. 2017, 19, 1982−1985. (72) Ge, L.; Lu, X.-H.; Cheng, C.; Chen, J.; Cao, W.-G.; Wu, X.-Y.; Zhao, G. Amide-Phosphonium Salt as Bifunctional Phase Transfer Catalyst for Asymmetric 1,6-Addition of Malonate Esters to paraQuinone Methides. J. Org. Chem. 2016, 81, 9315−9325. (73) Chu, W.-D.; Zhang, L.-F.; Bao, X.; Zhao, X.-H.; Zeng, C.; Du, J.Y.; Zhang, G.-B.; Wang, F.-X.; Ma, X.-Y.; Fan, C.-A. Asymmetric Catalytic 1,6-Conjugate Addition/ Aromatization of para-QuinoneMethides: Enantioselective Introduction of Functionalized DiarylmethineStereogenic Centers. Angew. Chem., Int. Ed. 2013, 52, 9229− 9233. (74) Huang, B.; Shen, Y.-Y.; Mao, Z.-J.; Liu, Y.; Cui, S.-L. Metathesis Reaction of Diazo Compounds and para-Quinone Methides for C−C Double Bond Formation: Synthesis of Tetrasubstituted Alkenes and Quinolinones. Org. Lett. 2016, 18, 4888−4891. (75) Dong, N.; Zhang, Z.-P.; Xue, X.-S.; Li, X.; Cheng, J.-P. Phosphoric Acid Catalyzed Asymmetric 1,6-Conjugate Addition of Thioacetic Acid to para-Quinone Methides. Angew. Chem., Int. Ed. 2016, 55, 1460−1464. (76) Yuan, Z.-B.; Fang, X.-X.; Li, X.-Y.; Wu, J.; Yao, H.-Q.; Lin, A. J. 1,6-Conjugated Addition-Mediated [2 + 1] Annulation: Approach to Spiro[2.5]octa-4,7-dien-6-one. J. Org. Chem. 2015, 80, 11123−11130. (77) Li, X.-Y.; Xu, X.-Y.; Wei, W.-W.; Lin, A.-L.; Yao, H.-Q. Organocatalyzed Asymmetric 1,6-Conjugate Addition of para-Quinone Methides with Dicyanoolefins. Org. Lett. 2016, 18, 428−431. (78) Mahesh, S.; Kant, G.; Anand, R. V. B(C6F5)3catalysed 1,6conjugate allylation of para-quinonemethides: expedient access to allyl diarylmethanes. RSC Adv. 2016, 6, 80718−80722. (79) Zhang, Z.-P.; Dong, N.; Li, X. Bismuth-catalyzed allylation of para-quinonemethides. Chem. Commun. 2017, 53, 1301−1304. (80) Zhao, K.; Zhi, Y.; Shu, T.; Valkonen, A.; Rissanen, K.; Enders, D. Organocatalytic Domino Oxa-Michael/1,6-Addition Reactions: Asymmetric Synthesis of Chromans Bearing Oxindole Scaffolds. Angew. Chem., Int. Ed. 2016, 55, 12104−12108. (81) Lou, Z.; Cao, P.; Jia, T.; Zhang, Y.; Wang, M.; Liao, J. CopperCatalyzed Enantioselective 1,6-Boration of para-Quinone Methides and Efficient Transformation of gem-DiarylmethineBoronates to Triarylmethanes. Angew. Chem., Int. Ed. 2015, 54, 12134−12138. (82) Kalisiak, J.; Ralph, E. C.; Cashman, J. R. Nonquaternary Reactivators for Organo-phosphate-Inhibited Cholinesterases. J. Med. Chem. 2012, 55, 465−474. (83) Fan, Y.-F.; Liu, S.; Chen, N.-Y.; Shao, X.-S.; Xu, X.-Y.; Li, Z. Oxidation strategy for the synthesis of regioisomericspiroisobenzofuranopyrroles: Facile entries to spiro[isobenzofuran-1,2′-pyrrole] and Spiro[isobenzofuran-1,3′-pyrrole] derivatives. Synlett 2015, 26, 393− 403. (84) Mertens, H.; Troschutz, R.; Roth, H. J. Synthese primarer Nitroketenaminale. Arch. Pharm. (Weinheim, Ger.) 1986, 319, 161− 167. (85) Alizadeh, A.; Bayat, F.; Zhu, Z. Efficient synthesis of chromenopyridines containing intramolecular hydrogen bonds through a sequential three-component reaction. Res. Chem. Intermed. 2016, 42, 5927−5936.

(86) Yaqub, M.; Perveen, R.; Shafiq, Z.; Pervez, H.; Tahir, M. N. Regioselective, catalyst-free, one-step synthesis of ABCD-fused heterocyclic ring system, closely related to Circumdatin alkaloids. Synlett 2012, 23, 1755−1758.

8389

DOI: 10.1021/acssuschemeng.7b02166 ACS Sustainable Chem. Eng. 2017, 5, 8382−8389