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Article

Gold(I)-Catalyzed Tandem Synthesis of Polycyclic Dihydroquinazolinones

by
Jingyang Sun
,
Yoona Song
and
Jae-Sang Ryu
*
College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-Gu, Seoul 03760, Korea
*
Author to whom correspondence should be addressed.
Catalysts 2021, 11(12), 1436; https://doi.org/10.3390/catal11121436
Submission received: 22 October 2021 / Revised: 19 November 2021 / Accepted: 23 November 2021 / Published: 25 November 2021
(This article belongs to the Special Issue Catalytic Organic Transformations/Organic Synthesis)
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Abstract

:
A gold-catalyzed cascade process for the synthesis of dihydroquinazolinone scaffolds was developed. A series of gold catalysts were screened for this tandem transformation, and the (PPh3)AuCl/AgOTf catalyst combination was found to be the best catalyst system. This method is characterized by good yields, high regioselectivity, and broad substrate scope. This method is also applicable to the synthesis of tetracyclic dihydroquinazolinones and seven-membered ring-fused dihydroquinazolinones.

Graphical Abstract

1. Introduction

Nitrogen-containing heterocycles [1,2,3] are important molecular architectures frequently found in bioactive natural products and drug candidates. As bioactive alkaloids [4,5,6], dihydroquinazolinones [7,8,9] are not only an important class of compounds but also substructures of structurally complex polycyclic alkaloids with a wide range of biological activities. More specifically, fused dihydroquinazolinones such as cruciferane [10], phaitanthrin D [11], evodiamine [12], and their synthetic congeners [13,14] have attracted medicinal chemists’ attention due to their unique structural features and promising bioactivities, which have prompted the research on synthetic dihydroquinazolinones with pharmacological potential (Figure 1). Although various synthetic approaches to bicyclic dihydroquinazolinone scaffolds have been described [15,16,17,18,19,20], effective strategies for more complex tri- and polycyclic dihydroquinazolinones, which operate under mild conditions on readily accessible simple substrates, are rare and of high value.
Thus far, a number of synthetic methodologies for various heterocyclic systems have been developed. Nevertheless, highly selective and efficient synthetic strategies, which allow a rapid increase in molecular complexity with a reduced number of transformation steps and purification processes, are still in demand. In this context, clean ‘one-pot cascade reactions’ [21,22,23,24,25] can reduce the number of synthetic steps and tedious purification processes. These reactions rapidly increase molecular complexity and diversity in a single operation in which reactive intermediates are produced and utilized for the next step of reaction without isolation. ‘One-pot cascade reactions’ may also save the time and labor required for multistep synthesis and minimize waste production during synthesis. Due to these advantages, ‘one-pot cascade reactions’ have emerged as an important tool for the efficient construction of more complicated polycyclic molecular skeletons.
Over the past two decades, homogeneous gold catalysis [26,27] has become one of the most promising fields in organic and organometallic chemistry. Due to its high reactivity toward π-systems and broad functional group compatibility, homogeneous gold catalysis has been established as a powerful tool for one-pot cascade reactions [28,29]. Gold catalysts act as carbophilic π-Lewis acids and efficiently activate C–C multiple bonds to form reactive intermediates [30], which further promote subsequent reactions with various types of partners. Specifically, when the activated C–C multiple bonds are combined with heteronucleophiles, enol/enamine-type reactive species are generated in situ, and several types of cascade cyclization reactions can be promoted (Scheme 1) [31,32]. Therefore, enol/enamine-type reactive species are considered as synthetically valuable and useful for gold-catalyzed one-pot cascade reactions [33,34]. Here, we have attempted to develop an efficient one-pot cascade synthetic method and report a gold-catalyzed one-pot cascade process for the synthesis of dihydroquinazolinones, which involves a double hydroamination process.

2. Results and Discussion

To investigate the feasibility of the gold-catalyzed one-pot cascade process for the synthesis of dihydroquinazolinone scaffolds, we initially focused on the double cascade cyclization of alkyne-tethered anthranilamide 1a as a benchmark substrate, which was readily prepared in one step from commercially available isatoic anhydride and 1-amino-4-pentyne. When 1a was subjected to a catalyst mixture of (PPh3)AuCl/AgOTf (10 mol%) dissolved in toluene, the substrate 1a was completely consumed at 60 °C in 5 h. The desired dihydroquinazolinone product 2a was obtained in 52% yield along with 6% of ketone byproduct 3a (Table 1, entry 1), which presumably was formed from the gold-catalyzed addition of H2O to the alkyne moiety of 1a. Although the formation of the ketone 3a was suppressed by the addition of the 4Å molecular sieve, it could not be completely prevented.
Initially, we optimized solvent conditions to screen for various cationic gold catalysts and silver cocatalysts. The double cascade cyclization reaction of 1a was investigated in various solvents including CH3CN, THF, CH2Cl2, 1,4-dioxane, cyclopentyl methyl ether (CPME), dimethyl carbonate (DMC), and dichloroethane (DCE) (Table 1, entries 2–8). The reactions were effective in all the solvents except CH3CN; only a small amount of product 2a was observed and isolated in the reaction in CH3CN (Table 1, entry 2). Considering the yield of the product, DCE was the best solvent for the reaction (Table 1, entry 8); thus, DCE was chosen for further study. We also briefly examined other Au/Ag catalyst combinations. The (PPh3)AuCl catalyst systems combined with AgNO3, AgBF4, AgOTs, and AgSbF6 were examined for cyclization at 60 °C in DCE solvent (Table 1, entries 9–12). The reactions using AgNO3, AgBF4, and AgOTs were fairly clean and comparable to the reaction with (PPh3)AuCl/AgOTf. Particularly, the reaction with (PPh3)AuCl/AgNO3 proceeded smoothly but slowly and provided the cyclic dihydroquinazolinone product 2a in 80% yield after 10 h (Table 1, entry 9).
Although the reaction was not effective with (PPh3)AuCl or AgOTf alone, a single (PPh3)AuNTf2 catalyst was as effective as the (PPh3)AuCl/AgOTf catalyst combination, which gave the desired double cyclized product 2a without silver (Table 1, entries 13 and 14 vs. entry 15). In comparison with (PPh3)AuCl or AgOTf alone, the improved reactivity of the (PPh3)AuCl/AgOTf catalyst combination may be attributed to the anion effect rather than the silver effect. Changing PPh3 with a biphenyl monodentate phosphine ligand (XPhos) did not improve the reactivity (Table 1, entry 16). The phosphine ligand was not essential for the reaction. Replacing the phosphine ligand PPh3 with IPr did not change the reactivity significantly (Table 1, entries 17–19). Interestingly, 10 mol% Brønsted acid (TfOH) did not catalyze the cyclization efficiently and generated the cyclized product 2a only in a trace amount (Table 1, entry 20). In addition, the effect of the catalyst loading on catalytic activity was also examined using 5 mol% and 1 mol% of (PPh3)AuCl/AgOTf (Table 1, entries 21 and 22). It is noteworthy that catalyst loading could be reduced to as low as 1 mol% with a slight decrease in yield (67%; Table 1, entry 22). Based on these observations, we chose to set the catalyst loading at 10 mol% for sterically hindered and unreactive substrates as shown in Table 2.
After identifying (PPh3)AuCl/AgOTf as the best catalyst, we investigated the scope of gold(I)-catalyzed one-pot cascade reactions for alkyne-tethered anthranilamides using (PPh3)AuCl/AgOTf at room temperature under optimized conditions (Table 2). The double cascade cyclization reaction worked well with a wide variety of alkyne-tethered anthranilamide substrates and showed broad functional group compatibility. When the (PPh3)AuCl/AgOTf catalyst combination was used at room temperature, the substrates 1b and 1c containing pentyne tethers smoothly provided double cyclized products (five-membered ring-fused dihydroquinazolinones 2b and 2c) in excellent yields (85% and 90%, entries 1 and 2). Likewise, the substrate 1d containing a fused-aromatic substituent on the tether also readily underwent double cascade cyclization and afforded the corresponding dihydroquinazolinone product 2d in 98% yield (entry 3). Furthermore, the double cascade cyclization reaction worked well with the internal alkyne substrate 1e, which was smoothly cyclized to 2e at 60 °C in 80% yield (entry 4). However, the reaction with the phenyl substituted internal alkyne substrate 1f needed a higher temperature for cyclization due to the unfavorable electronic and steric effects of the phenyl group. Interestingly, the reaction of 1f provided the five-membered ring-fused dihydroquinazolinone 2f (entry 5). Although coordination of the π-acidic cationic gold catalyst to alkyne may increase the electrophilic nature of the benzylic position, 5-exo-dig cyclization was more favored than 6-endo-dig cyclization (Scheme 2).
On the other hand, the double cascade reaction was also effective for the synthesis of six-membered ring-fused dihydroquinazolinones. However, six-membered ring formation was slower than five-membered ring formation at ambient temperature owing to the higher energy barrier for ring closure. Therefore, the reaction was carried out at 120 °C under sealed-tube conditions in a microwave reactor; the substrates 1g–j containing hexyne tethers and 1k containing a fused-aromatic substituent on the tether were converted into the corresponding six-membered ring-fused dihydroquinazolinones 2g–k in moderate yields (30–75%, entries 6–10). Notably, this reaction worked well for seven-membered ring formation as well. Despite unfavorable enthalpic and entropic factors associated with seven-membered ring closure [35,36,37], our method was applicable to the synthesis of the seven-membered ring-fused dihydroquinazolinone 2l, which was obtained in 31% yield in the presence of (IPr)AuCl/AgOTf at 120 °C in 1 h (entry 11).
Next, we investigated the substrate scope with respect to the electronic effect of substituents. The method showed good compatibility for electron-withdrawing and electron-donating functional groups such as chloro, bromo, nitro, alkyl, and methoxy groups. The substrates containing electron-withdrawing substituents (1m–p) smoothly afforded the cyclized products 2m–p at room temperature in excellent yields (92–97%, entries 12–15). The substrates containing electron-donating substituents (1q–t) also provided the corresponding cyclized products in good to excellent yields (72–91%, entries 16–19). Furthermore, the reaction was tolerant of the N-alkyl substituent of the anthranilamide substrate; the N-methyl substituent of the anthranilamide substrate 1u did not affect the second cyclization reaction and afforded the dihydroquinazolinone 2u in 97% yield at 60 °C.
Based on our observation and previous reports about gold(I)-catalyzed alkyne hydroamination [38,39], the possible mechanism is proposed in Scheme 3. First, the gold(I) chloride complex precursor condenses with silver salts, which would scavenge chloride ions as insoluble AgCl and generate the active gold(I) catalyst A. The coordination of the active gold(I) species A to the alkyne moiety of the substrate 1a leads to the formation of the gold π-alkyne complex B, which could be cyclized to the gold–alkyl complex C or hydrated to the ketone 3a by the adventitious addition of water. Upon the protodeauration of C, the enamine intermediate D is released, and the active gold(I) catalyst A is regenerated. Next, the second cyclization reaction would begin with the re-coordination of the π-acidic cationic gold catalyst A to the alkene moiety of the enamine intermediate D, which catalyzes the formation of the iminium intermediate E and accelerates the second intramolecular cyclization reaction. The resultant gold–alkyl complex F readily undergoes protodeauration and decomposes to yield the double cyclized product 2a and the cationic gold(I) catalyst A. This proposed mechanism involves repeated coordination and subsequent cyclization mediated by the gold(I) catalyst.

3. Materials and Methods

3.1. General Information

All reactions were performed in oven-dried glassware fitted with glass stoppers under positive pressure of Ar with magnetic stirring, unless otherwise noted. Air- and moisture-sensitive liquids and solutions were transferred via syringe or stainless-steel cannula. TLC was performed on 0.25 mm E. Merck (Darmstadt, Germany) silica gel 60 F254 plates and visualized under UV light (254 nm) or by staining with cerium ammonium molybdenate (CAM), potassium permanganate (KMnO4), ninhydrin, or p-anisaldehyde. Flash chromatography was performed on E. Merck (Darmstadt, Germany) 230–400 mesh silica gel 60. Medium-pressure liquid chromatography (MPLC) was performed on a prepacked column (silica gel, 10 μm) with a UV detector. Reagents were purchased from commercial suppliers and used without further purification unless otherwise noted. Solvents were distilled from proper drying agents (CaH2 or Na wire) under Ar atmosphere at 760 mmHg. All moisture- and/or oxygen-sensitive solids were handled and stored in a glovebox under N2. NMR spectra were recorded on Agilent (Santa Clara, CA, USA) Unity 400 instruments or Bruker (Billerica, MA, USA) Avene II 400 MHz NMR spectrometer system equipped at Ewha Drug Development Research Core Center at 24 °C. Chemical shifts are expressed in ppm relative to TMS (1H, 0 ppm), CDCl3 (1H, 7.26 ppm; 13C, 77.2 ppm), DMSO-d6 (1H, 2.50 ppm; 13C, 39.5 ppm), C6D6 (1H, 7.16 ppm; 13C, 128.1 ppm), CD3OD (1H, 3.31 ppm; 13C, 49.1 ppm); coupling constants are expressed in Hz. High resolution mass spectra (HRMS) were obtained by electrospray ionization (ESI, TOF), electron ionization (EI, magnetic sector), Chemical ionization (CI, magnetic sector), or fast atom bombardment (FAB, magnetic sector). Infrared spectra were recorded with peaks reported in cm−1 (see Supplementary Materials).

3.2. Representative Procedure for the Synthesis of Dihydroquinazolinone 2a–u

To a 10 mL oven-dried round-bottom flask with a side arm were added 1b (92.1 mg, 400 μmol) and 4Å MS (500 mg). The flask was brought into the glovebox, and (PPh3)AuCl (19.8 mg, 40.0 μmol, 10 mol%) and AgOTf (10.3 mg, 40.0 μmol, 10 mol%) were added inside a glovebox. Then, the flask was brought out of the glovebox, and anhydrous DCE (4.0 mL) was added. The reaction mixture was stirred at room temperature for 1.5 h. Upon completion of the reaction, the precipitate was filtered off through a pad of Celite® and rinsed with CH2Cl2 (50 mL). The filtrate was concentrated by rotary evaporation. The residue was purified by column chromatography (1.5:1 hexanes/EtOAc) to afford dihydroquinazolinone 2b (78.5 mg, 340 μmol, 85%) as a white solid.

3.2.1. 3a-Methyl-2,3,3a,4-tetrahydropyrrolo[2,1-b]quinazolin-9(1H)-one (2a)

Reaction time: 1 h (60 °C). White solid (64.7 mg, 80%). TLC: Rf 0.08 (1:1 hexane/EtOAc). mp: 168.9–170.9 °C. 1H NMR (400 MHz, C6D6): δ 8.36 (dd, J = 7.6, 1.6 Hz, 1H), 7.09–6.98 (m, 1H), 6.71 (td, J = 7.5, 1.0 Hz, 1H), 6.31–6.24 (m, 1H), 3.69 (dt, J = 12.2, 8.1 Hz, 1H), 3.47 (brs, 1H), 3.45–3.37 (m, 1H), 1.60–1.51 (m, 1H), 1.37–1.30 (m, 2H), 1.27–1.18 (m, 1H), 0.88 (s, 3H). 13C NMR (100 MHz, C6D6): δ 160.8, 146.2, 132.8, 128.9, 119.4, 118.1, 115.0, 75.0, 44.4, 40.6, 24.9, 21.0. HRMS (ESI) m/z calcd for C12H15N2O [M + H]+ 203.1179, found 203.1179.
Ketone 3a: Colorless liquid. TLC: Rf 0.14 (1:1 hexane/EtOAc). 1H NMR (400 MHz, C6D6): δ 7.24–7.17 (m, 1H), 7.12 (td, J = 7.6, 1.2 Hz, 1H), 6.60 (td, J = 7.6, 1.2 Hz, 1H), 6.40–6.33 (m, 1H), 5.98 (brs, 1H), 5.65 (brs, 2H), 3.25 (q, J = 6.4 Hz, 2H), 1.94 (t, J = 6.8 Hz, 2H), 1.67 (s, 3H), 1.60 (p, J = 6.8 Hz, 2H). 13C NMR (100 MHz, C6D6): δ 207.3, 169.5, 149.9, 132.2, 127.6, 117.3, 116.1, 116.1, 40.8, 39.4, 29.4, 23.6. HRMS (ESI) m/z calcd for C12H17N2O2 [M + H]+ 221.1285, found 221.1287.

3.2.2. 2,2,3a-Trimethyl-2,3,3a,4-tetrahydropyrrolo[2,1-b]quinazolin-9(1H)-one (2b)

Reaction time: 1.5 h (room temperature). White solid (78.5 mg, 85%). TLC: Rf 0.25 (1.5:1 hexanes/EtOAc). mp: 172.3–174.3 °C. 1H NMR (400 MHz, CDCl3): δ 7.89 (ddt, J = 7.8, 1.5, 0.6 Hz, 1H), 7.27 (ddd, J = 8.0, 7.3, 1.6 Hz, 1H), 6.85 (ddd, J = 7.8, 7.3, 1.0 Hz, 1H), 6.62 (ddd, J = 8.0, 1.0, 0.5 Hz, 1H), 4.18 (brs, 1H), 3.95 (dd, J = 11.6, 1.6 Hz, 1H), 3.13 (dd, J = 11.6, 0.8 Hz, 1H), 2.05 (dd, J = 13.1 Hz, 1.6 Hz, 1H), 1.97 (d, J = 13.1 Hz, 2H), 1.48 (s, 3H), 1.21 (s, 3H), 1.19 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 161.2, 145.7, 133.2, 128.6, 119.4, 116.7, 115.1, 76.1, 57.6, 55.6, 37.5, 28.3, 27.4, 27.2. HRMS (ESI) m/z calcd for C14H19N2O [M + H]+ 231.1492, found 231.1488.

3.2.3. 3a′-Methyl-3a′,4′-dihydro-1′H-spiro[cyclohexane-1,2′-pyrrolo[2,1-b]quinazolin]-9′(3′H)-one (2c)

Reaction time: 3 h (room temperature). White solid (96.9 mg, 90%). TLC: Rf 0.25 (3:1 hexanes/EtOAc). mp: 241.1–243.1 °C. 1H NMR (400 MHz, C6D6): δ 8.39 (dd, J = 7.5, 1.6 Hz, 1H), 7.05 (ddd, J = 8.0, 7.5, 1.6 Hz, 1H), 6.72 (td, J = 7.5, 1.1 Hz, 1H), 6.21 (dd, J = 8.0, 1.1 Hz, 1H), 4.26 (d, J = 11.9 Hz, 1H), 3.28 (brs, 1H), 2.85 (d, J = 11.9 Hz, 1H), 1.59 (d, J = 13.0 Hz, 1H), 1.30 (d, J = 13.0 Hz, 1H), 1.38–1.04 (m, 10H), 1.00 (s, 3H). 13C NMR (100 MHz, C6D6): δ 160.6, 146.0, 132.8, 129.2, 119.4, 117.6, 114.9, 75.0, 40.7, 37.3, 36.3, 26.8, 26.1, 24.1, 23.3. HRMS (ESI) m/z calcd for C17H23N2O [M + H]+ 271.1805, found 271.1807.

3.2.4. 4b-Methyl-4b,12-dihydroisoindolo[1,2-b]quinazolin-10(5H)-one (2d)

Reaction time: 1 h (room temperature). White solid (98.1 mg, 98%). TLC: Rf 0.26 (1:1 hexane/EtOAc). mp: 159.2–161.2 °C. 1H NMR (400 MHz, CDCl3): δ 8.00 (dd, J = 7.8, 1.6 Hz, 1H), 7.45–7.32 (m, 5H), 7.02–6.93 (m, 1H), 6.87–6.80 (m, 1H), 5.14 (d, J = 15.8 Hz, 1H), 4.76 (d, J = 15.8 Hz, 1H), 4.49 (brs, 1H), 1.66 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 161.4, 144.7, 143.3, 135.8, 133.5, 129.2, 128.6, 128.3, 123.7, 120.8, 120.7, 118.8, 117.1, 78.7, 50.1, 27.5. HRMS (ESI) m/z calcd for C16H15N2O [M + H]+ 251.1179, found 251.1182.

3.2.5. 3a-Ethyl-2,2-dimethyl-2,3,3a,4-tetrahydropyrrolo[2,1-b]quinazolin-9(1H)-one (2e)

Reaction time: 24 h, (60 °C). White solid (77.8 mg, 80%). TLC: Rf 0.18 (3:1 hexanes/EtOAc). mp: 44.2–46.2 °C. 1H NMR (400 MHz, CDCl3): δ 7.87 (dd, J = 7.8, 1.6 Hz, 1H), 7.31–7.22 (m, 1H), 6.84 (ddd, J = 7.8, 7.3, 1.1 Hz, 1H), 6.65–6.58 (m, 1H), 4.37 (brs, 1H), 3.99 (dd, J = 11.6, 1.8 Hz, 1H), 3.10 (dd, J = 11.6, 0.8 Hz, 1H), 2.01 (d, J = 13.2 Hz, 1H), 1.94 (dq, J = 13.6, 7.4 Hz, 1H), 1.84 (dd, J = 13.2, 1.7 Hz, 1H), 1.66 (dq, J = 13.6, 7.4 Hz, 1H), 1.21 (s, 3H), 1.18 (s, 3H), 0.86 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 161.4, 145.4, 133.2, 128.6, 119.2, 117.1, 114.9, 78.8, 58.4, 52.2, 37.7, 31.9, 28.1, 26.9, 8.5. HRMS (ESI) m/z calcd for C15H21N2O [M + H]+ 245.1648, found 245.1649.

3.2.6. 5a-Phenyl-5,5a,6,7,8,9-hexahydro-11H-pyrido[2,1-b]quinazolin-11-one (2f)

Reaction time: 4 h (120 °C). White solid (11.5 mg, 10%). The reaction mixture was irradiated with microwave in a 5 mL microwave process vial. TLC: Rf 0.15 (2:1 hexanes/EtOAc). mp: 151.1–153.1 °C. 1H NMR (400 MHz, CDCl3): δ 7.94 (dd, J = 7.7, 1.6 Hz, 1H), 7.40–7.27 (m, 4H), 7.12–7.04 (m, 2H), 6.90 (td, J = 7.5, 1.0 Hz, 1H), 6.66 (ddd, J = 8.0, 1.1, 0.5 Hz, 1H), 4.52 (brs, 1H), 3.95–3.83 (m, 1H), 3.72–3.61 (m, 1H), 3.18 (dd, J = 13.3, 1.3 Hz, 1H), 2.79 (d, J = 13.3 Hz, 1H), 2.38–2.29 (m, 1H), 2.14–2.01 (m, 1H), 2.01–1.82 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 161.6, 145.3, 136.2, 133.6, 130.4, 128.8, 128.6, 127.3, 119.6, 117.6, 115.1, 77.8, 45.1, 41.9, 36.8, 21.1. HRMS (ESI) m/z calcd for C18H19N2O [M + H]+ 279.1492, found 279.1494.
Ketone 3f: Ivory solid (6.8 mg, 6%). TLC: Rf 0.50 (1:1 hexane/EtOAc). 1H NMR (400 MHz, CDCl3): δ 8.01–7.93 (m, 2H), 7.61–7.52 (m, 1H), 7.51–7.42 (m, 2H), 7.36 (dd, J = 7.8, 1.5 Hz, 1H), 7.20 (ddd, J = 8.5, 7.2, 1.5 Hz, 1H), 6.71–6.62 (m, 2H), 6.30 (s, 1H), 5.50 (s, 2H), 3.46 (td, J = 6.8, 5.7 Hz, 2H), 3.06 (t, J = 6.8 Hz, 2H), 1.92–1.80 (m, 2H), 1.76–1.65 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 200.3, 169.5, 148.8, 137.0, 133.3, 132.3, 128.8, 128.2, 127.3, 117.4, 116.8, 116.4, 39.4, 38.1, 29.3, 21.3. HRMS (ESI) m/z calcd for C18H21N2O2 [M + H]+ 297.1598, found 297.1601.

3.2.7. 5a-Methyl-5,5a,6,7,8,9-hexahydro-11H-pyrido[2,1-b]quinazolin-11-one (2g)

Reaction time: 1 h (120 °C). White solid (25.7 mg, 30%). The reaction mixture was irradiated with microwave in a 5 mL microwave process vial. TLC: Rf 0.20 (2:1 hexanes/EtOAc). mp: 139.8–141.8 °C. 1H NMR (400 MHz, CDCl3): δ 7.90 (dd, J = 7.9, 1.6 Hz, 1H), 7.31–7.22 (m, 1H), 6.80 (ddd, J = 7.9, 7.3, 1.0 Hz, 1H), 6.56 (d, J = 7.9, 1.0 Hz, 1H), 4.54 (m, 1H), 4.03 (brs, 1H), 2.74 (m, 1H), 1.98–1.89 (m, 1H), 1.87–1.81 (m, 3H), 1.65–1.50 (m, 2H), 1.47 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 163.9, 144.7, 133.6, 128.9, 118.9, 115.8, 114.3, 70.7, 39.2, 38.6, 24.4, 22.3, 20.6. HRMS (ESI) m/z calcd for C13H17N2O [M + H]+ 217.1335, found 217.1335.
Ketone 3g: Colorless liquid (14.0 mg, 15%). TLC: Rf 0.15 (1.5:1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3): δ 7.34 (dd, J = 7.9, 1.5 Hz, 1H), 7.20 (ddd, J = 8.5, 7.2, 1.5 Hz, 1H), 6.71–6.61 (m, 2H), 6.24 (s, 1H), 5.50 (s, 2H), 3.40 (td, J = 6.6, 5.6 Hz, 2H), 2.51 (t, J = 6.8 Hz, 2H), 2.15 (s, 3H), 1.73–1.59 (m, 4H). 13C NMR (100 MHz, CDCl3): δ 163.9, 144.7, 133.6, 128.9, 118.9, 115.8, 114.3, 70.7, 39.7, 38.6, 24.4, 22.3, 20.6. HRMS (ESI) m/z calcd for C13H19N2O2 [M + H]+ 235.1441, found 235.1442.

3.2.8. 2-methoxy-5a-methyl-5,5a,6,7,8,9-hexahydro-11H-pyrido[2,1-b]quinazolin-11-one (2h)

Reaction time: 2.5 h (120 °C). A total of 754 μmol of 1h was used. White solid (175 mg, 94%). The reaction mixture was irradiated with microwave in a 5 mL microwave process vial. TLC: Rf 0.30 (2:1 hexanes/EtOAc). mp: 146.7–147.8 °C. 1H NMR (400 MHz, DMSO-d6): δ 7.14 (d, J = 3.0 Hz, 1H), 6.91 (dd, J = 8.7, 3.0 Hz, 1H), 6.61 (d, J = 8.7 Hz, 1H), 6.34 (s, 1H), 4.35–4.13 (m, 1H), 3.67 (s, 3H), 2.65 (td, J = 13.4, 3.5 Hz, 1H), 1.90–1.65 (m, 4H), 1.62–1.34 (m, 2H), 1.32 (s, 3H). 13C NMR (100 MHz, DMSO-d6): δ 162.7, 151.1, 140.4, 121.3, 115.7, 114.5, 110.3, 70.4, 55.3, 38.0, 37.8, 24.0, 20.9, 19.8. HRMS (EI) m/z calcd for C14H18N2O2 [M]+ 246.1368, found 246.1364.

3.2.9. 2,3-dimethoxy-5a-methyl-5,5a,6,7,8,9-hexahydro-11H-pyrido[2,1-b]quinazolin-11-one (2i)

Reaction time: 1.25 h (120 °C). A total of 719 μmol of 1i was used. White solid (167 mg, 84%). The reaction mixture was irradiated with microwave in a 5 mL microwave process vial. TLC: Rf 0.30 (1:1 hexanes/EtOAc). mp: 195.5–196.7 °C. 1H NMR (400 MHz, DMSO-d6): δ 7.09 (s, 1H), 6.40 (s, 1H), 6.22 (s, 1H), 4.22 (dd, J = 12.4, 4.3 Hz, 1H), 3.74 (s, 3H), 3.66 (s, 3H), 2.61 (td, J = 13.5, 3.3 Hz, 1H), 1.87–1.65 (m, 4H), 1.62–1.44 (m, 1H), 1.37 (td, J = 8.8, 4.3 Hz, 1H), 1.32 (s, 3H). 13C NMR (100 MHz, DMSO-d6): δ 162.8, 153.9, 141.8, 141.1, 110.4, 105.5, 97.5, 70.4, 55.9, 55.3, 38.1, 37.7, 24.1, 20.6, 19.9. HRMS (ESI) m/z calcd for C15H21N2O3 [M + H]+ 277.1547, found 277.1546.

3.2.10. 5a,8,8-Trimethyl-5,5a,6,7,8,9-hexahydro-11H-pyrido[2,1-b]quinazolin-11-one (2j)

Reaction time: 20 min (120 °C). White solid (55.2 mg, 57%). The reaction mixture was irradiated with microwave in a 5 mL microwave process vial. TLC: Rf 0.20 (2:1 hexanes/EtOAc). mp: 121.6–123.6 °C. 1H NMR (400 MHz, CDCl3): δ 7.91 (dd, J = 7.8, 1.6 Hz, 1H), 7.27 (m, 1H), 6.81 (td, J = 7.5, 1.1 Hz, 1H), 6.57 (dd, J = 8.1, 1.1 Hz, 1H), 4.22 (dd, J = 13.7, 1.9 Hz, 1H), 4.03 (brs, 1H), 2.49 (dd, J = 13.7, 0.8 Hz, 1H), 2.13 (td, J = 12.7, 5.5 Hz, 1H), 1.72 (dt, J = 12.7, 4.1 Hz, 1H), 1.54–1.45 (m, 2H), 1.44 (d, J = 0.8 Hz, 3H), 1.03 (s, 3H), 1.02 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 164.0, 144.7, 133.6, 128.9, 118.9, 114.3, 77.4, 70.3, 49.1, 35.7, 33.8, 30.1, 29.0, 23.9, 22.4. HRMS (ESI) m/z calcd for C15H21N2O [M + H]+ 245.1648, found 245.1651.

3.2.11. 13a-Methyl-5,6,13,13a-tetrahydro-8H-isoquinolino[1,2-b]quinazolin-8-one (2k)

Reaction time: 1 h (120 °C). White solid (64.6 mg, 61%). The reaction mixture was irradiated with microwave in a 5 mL microwave process vial. TLC: Rf 0.20 (2:1 hexanes/EtOAc). mp: 187.3–189.3 °C. 1H NMR (400 MHz, CDCl3): δ 8.01 (dd, J = 7.9, 1.5 Hz, 1H), 7.42 (dd, J = 7.9, 1.5 Hz, 1H), 7.39–7.28 (m, 3H), 7.21 (dd, J = 7.5, 1.6 Hz, 1H), 6.92 (ddd, J = 8.2, 7.3, 1.1 Hz, 1H), 6.76–6.70 (m, 1H), 5.07–4.94 (m, 1H), 4.36 (brs, 1H), 3.12–2.95 (m, 2H), 2.89–2.76 (m, 1H), 1.78 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 162.7, 144.4, 138.9, 134.6, 133.6, 129.6, 129.0, 128.2, 127.5, 124.6, 120.0, 117.3, 116.2, 71.5, 36.0, 29.2, 26.3. HRMS (ESI) m/z calcd for C17H17N2O [M + H]+ 265.1335, found 265.1336.

3.2.12. 5a,9,9-Trimethyl-5a,6,7,8,9,10-hexahydroazepino[2,1-b]quinazolin-12(5H)-one (2l)

Reaction time: 1 h (120 °C). White solid (31.5 mg, 31%). The reaction mixture was irradiated with microwave in a 5 mL microwave process vial. TLC: Rf 0.25 (4:1 hexanes/EtOAc). mp: 177.9–179.9 °C. 1H NMR (400 MHz, CDCl3): δ 7.87 (dd, J = 7.5, 1.6 Hz, 1H), 7.24 (ddd, J = 8.0, 7.5, 1.6 Hz, 1H), 6.78 (td, J = 7.5, 1.0. Hz, 1H), 6.59 (dd, J = 8.0, 1.0 Hz, 1H), 4.29 (dd, J = 14.1, 2.1 Hz, 1H), 4.10 (brs, 1H), 2.62 (d, J = 14.1 Hz, 1H), 2.21–2.04 (m, 1H), 1.98–1.75 (m, 2H), 1.59–1.43 (m, 2H), 1.40 (s, 3H), 1.29–1.14 (m, 1H), 0.96 (s, 3H), 0.91 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 164.0, 145.6, 133.3, 129.1, 118.9, 115.8, 114.5, 74.3, 49.3, 44.8, 43.8, 35.5, 29.7, 25.6, 23.4, 19.2. HRMS (ESI) m/z calcd for C16H23N2O [M + H]+ 259.1805, found 259.1806.
Ketone 3l: Colorless liquid (18.8 mg, 17%). TLC: Rf 0.08 (4:1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3): δ 7.43 (dd, J = 8.1, 1.5 Hz, 1H), 7.23–7.15 (m, 1H), 6.71–6.62 (m, 2H), 6.49 (s, 1H), 5.48 (s, 2H), 3.28 (d, J = 6.4 Hz, 2H), 2.44 (t, J = 6.7 Hz, 2H), 2.13 (s, 3H), 1.62–1.50 (m, 2H), 1.23–1.16 (m, 2H), 0.92 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 209.4, 169.6, 148.8, 132.2, 127.3, 117.3, 116.8, 116.7, 48.1, 43.8, 39.0, 34.8, 30.2, 25.4, 17.9. HRMS (ESI) m/z calcd for C16H25N2O2 [M + H]+ 277.1911, found 277.1913.

3.2.13. 8-Chloro-4b-methyl-4b,12-dihydroisoindolo[1,2-b]quinazolin-10(5H)-one (2m)

Reaction time: 30 min (room temperature). White solid (109.8 mg, 96%). TLC: Rf 0.34 (2:1 hexane/EtOAc). mp: 207.3–209.2 °C. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 2.5 Hz, 1H), 7.45–7.35 (m, 4H), 7.30 (dd, J = 8.5, 2.5 Hz, 1H), 6.80 (d, J = 8.5 Hz, 1H), 5.10 (d, J = 15.8 Hz, 1H), 4.74 (d, J = 15.8 Hz, 1H), 4.67 (brs, 1H), 1.65 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.3, 143.2, 142.8, 135.5, 133.5, 129.3, 128.4, 128.2, 125.8, 123.7, 120.8, 119.8, 118.6, 78.9, 50.1, 27.5. HRMS (ESI) m/z calcd for C16H14ClN2O [M + H]+ 285.0789, found 285.0789.

3.2.14. 7-Chloro-4b-methyl-4b,12-dihydroisoindolo[1,2-b]quinazolin-10(5H)-one (2n)

Reaction time: 30 min (room temperature). White solid (110.7 mg, 97%). TLC: Rf 0.28 (2:1 hexane/EtOAc). mp: 232.3–233.7 °C. 1H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 8.3 Hz, 1H), 7.44–7.39 (m, 3H), 7.39–7.33 (m, 1H), 6.92 (dd, J = 8.3, 1.9 Hz, 1H), 6.83 (d, J = 1.9 Hz, 1H), 5.12 (d, J = 16.0 Hz, 1H), 4.74 (d, J = 16.0 Hz, 1H), 4.57 (brs, 1H), 1.67 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.2, 143.6, 142.8, 136.3, 135.5, 131.2, 129.3, 128.4, 123.7, 120.8, 120.0, 118.8, 112.7, 78.9, 50.1, 27.5. HRMS (ESI) m/z calcd for C16H14ClN2O [M + H]+ 285.0789, found 285.0790.

3.2.15. 8-Bromo-4b-methyl-4b,12-dihydroisoindolo[1,2-b]quinazolin-10(5H)-one (2o)

Reaction time: 2 h (room temperature). White solid (121.6 mg, 92%). TLC: Rf 0.28 (2:1 hexane/EtOAc). mp: 213.1–215.1 °C. 1H NMR (400 MHz, CDCl3): δ 8.11 (d, J = 2.3 Hz, 1H), 7.45 (dd, J = 8.5, 2.4 Hz, 1H), 7.42–7.39 (m, 3H), 7.39–7.35 (m, 1H), 6.73 (d, J = 8.5 Hz, 1H), 5.12 (d, J = 16.0 Hz, 1H), 4.75 (d, J = 16.0 Hz, 1H), 4.48 (brs, 1H), 1.66 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.2, 143.6, 142.8, 136.3, 135.5, 131.2, 129.3, 128.4, 123.7, 120.8, 120.0, 118.8, 112.7, 78.9, 50.1, 27.5. HRMS (ESI) m/z calcd for C16H14BrN2O [M + H]+ 329.0284, found 329.0285.

3.2.16. 4b-methyl-7-nitro-4b,12-dihydroisoindolo[1,2-b]quinazolin-10(5H)-one (2p)

Reaction time: 30 min (room temperature). Yellow solid (114.8 mg, 97%). TLC: Rf 0.25 (1:1 hexane/EtOAc). mp: 279.1–281.4 °C. 1H NMR (400 MHz, DMSO-d6): δ 8.15 (brs, 1H), 7.93 (d, J = 8.5 Hz, 1H), 7.68 (d, J = 2.3 Hz, 1H), 7.62–7.53 (m, 2H), 7.51–7.36 (m, 3H), 4.99 (d, J = 16.0 Hz, 1H), 4.70 (d, J = 16.0 Hz, 1H), 1.58 (s, 3H). 13C NMR (100 MHz, DMSO-d6): δ 158.5, 150.7, 146.9, 142.8, 134.7, 129.2, 128.7, 128.0, 123.5, 121.3, 120.0, 111.9, 109.8, 78.5, 49.5, 27.1. HRMS (ESI) m/z calcd for C16H14N3O3 [M + H]+ 296.1030, found 296.1031.

3.2.17. 4b,8-Dimethyl-4b,12-dihydroisoindolo[1,2-b]quinazolin-10(5H)-one (2q)

Reaction time: 8 h (room temperature). White solid (96.2 mg, 91%). TLC: Rf 0.14 (2:1 hexane/EtOAc). mp: 191.2–192.7 °C. 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J = 1.6 Hz, 1H), 7.49–7.42 (m, 1H), 7.39–7.28 (m, 3H), 7.16 (dd, J = 8.2, 2.0 Hz, 1H), 6.84 (d, J = 8.2 Hz, 1H), 5.11 (brs, 1H), 5.06 (d, J = 15.8 Hz, 1H), 4.69 (d, J = 15.8 Hz, 1H), 2.29 (s, 3H), 1.63 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 161.5, 143.2, 142.1, 135.6, 134.4, 130.4, 129.0, 128.4, 128.2, 123.5, 121.2, 118.9, 117.8, 78.9, 49.9, 27.0, 20.7. HRMS (ESI) m/z calcd for C17H17N2O [M + H]+ 265.1335, found 265.1335.

3.2.18. 8-Methoxy-4b-methyl-4b,12-dihydroisoindolo[1,2-b]quinazolin-10(5H)-one (2r)

Reaction time: 24 h (room temperature). White solid (84.7 mg, 76%). TLC: Rf 0.26 (1:2 hexane/EtOAc). mp: 192.5–193.8 °C. 1H NMR (400 MHz, CDCl3): δ 7.54 (d, J = 2.9 Hz, 1H), 7.44–7.37 (m, 4H), 7.01 (dd, J = 8.7, 3.0 Hz, 1H), 6.90 (d, J = 8.7 Hz, 1H), 5.12 (d, J = 15.9 Hz, 1H), 4.75 (d, J = 15.9 Hz, 1H), 3.85 (s, 3H), 1.61 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 161.2, 155.0, 143.4, 137.9, 135.9, 129.2, 128.3, 123.6, 121.5, 121.4, 121.3, 120.9, 110.7, 79.1, 55.9, 49.8, 27.1. HRMS (ESI) m/z calcd for C17H16N2NaO2 [M + Na]+ 303.1104, found 303.1107.

3.2.19. 7,8-dimethoxy-4b-methyl-4b,12-dihydroisoindolo[1,2-b]quinazolin-10(5H)-one (2s)

Reaction time: 3 h (room temperature). White solid (88.9 mg, 72%). TLC: Rf 0.22 (1:1 hexane/EtOAc). mp: 154.6–156.1 °C. 1H NMR (400 MHz, CD3OD): δ 7.55–7.49 (m, 1H), 7.46–7.38 (m, 3H), 7.33 (s, 1H), 6.50 (s, 1H), 5.01 (d, J = 15.9 Hz, 1H), 4.70 (d, J = 15.9 Hz, 1H), 3.87 (s, 3H), 3.82 (s, 3H), 1.62 (s, 3H). 13C NMR (100 MHz, CD3OD): δ 163.6, 156.3, 144.8, 144.3, 143.8, 136.4, 129.9, 129.2, 124.3, 122.3, 111.4, 109.0, 100.5, 80.4, 57.0, 56.3, 50.7, 26.2. HRMS (ESI) m/z calcd for C18H19N2O3 [M + H]+ 311.1390, found 311.1393.

3.2.20. 6,7,8-trimethoxy-4b-methyl-4b,12-dihydroisoindolo[1,2-b]quinazolin-10(5H)-one (2t)

Reaction time: 1 h (room temperature). White solid (116.5 mg, 86%). TLC: Rf 0.16 (1:1 hexane/EtOAc). mp: 190.4–192.4 °C. 1H NMR (400 MHz, CDCl3): δ 7.43 (dtd, J = 5.7, 3.1, 1.1 Hz, 1H), 7.41–7.33 (m, 3H), 7.28 (s, 1H), 5.10 (d, J = 15.8 Hz, 1H), 4.81 (brs, 1H), 4.74 (d, J = 15.8 Hz, 1H), 3.94 (s, 3H), 3.88 (s, 3H), 3.86 (s, 3H), 1.64 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.9, 146.9, 146.4, 143.1, 141.0, 135.4, 133.7, 128.9, 128.1, 123.4, 120.8, 112.1, 105.7, 79.0, 60.9, 60.9, 56.3, 50.0, 26.8. HRMS (ESI) m/z calcd for C19H20N2NaO4 [M + Na]+ 363.1315, found 363.1318.

3.2.21. 4b,5-dimethyl-4b,12-dihydroisoindolo[1,2-b]quinazolin-10(5H)-one (2u)

Reaction time: 1.5 h (60 °C). White solid (102.5 mg, 97%). TLC: Rf 0.15 (5:1 hexane/EtOAc). mp: 133.0–134.8 °C. 1H NMR (400 MHz, CDCl3): δ 8.05 (dd, J = 7.7, 1.4 Hz, 1H), 7.55–7.44 (m, 2H), 7.44–7.38 (m, 3H), 7.14–7.03 (m, 2H), 5.13 (d, J = 15.9 Hz, 1H), 4.81 (d, J = 15.9 Hz, 1H), 2.74 (s, 3H), 1.54 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 161.5, 149.0, 140.7, 136.4, 133.4, 129.2, 128.1, 127.7, 124.4, 123.7, 122.4, 121.9, 119.7, 83.4, 50.4, 37.1, 25.5. HRMS (ESI) m/z calcd for C17H16N2NaO [M + Na]+ 287.1155, found 287.1158.

4. Conclusions

In conclusion, we developed a gold(I)-catalyzed one-pot cascade process for alkyne-tethered anthranilamides, which allows facile access to polycyclic dihydroquinazolinones in good to excellent yields under mild reaction conditions. This one-pot cascade methodology is widely applicable to the synthesis of bioactive privileged natural product scaffolds and offers a straightforward approach to increase molecular complexity and structural diversity in a few synthetic steps. The use of this method to construct polycyclic dihydroquinazolinone-like libraries is currently underway in our laboratory.

Supplementary Materials

The following are available online at https://www.mdpi.com/article/10.3390/catal11121436/s1, detailed synthetic procedure of 1a–u and copies of 1H and 13C NMR spectra of 1a–u and 2a–u.

Author Contributions

Conceptualization, J.-S.R.; investigation, experimental, and analysis, J.S., Y.S., and J.-S.R.; resources, J.-S.R.; data curation, J.S. and J.-S.R.; writing—original draft preparation, J.-S.R.; writing—review and editing, J.S. and J.-S.R.; supervision, J.-S.R.; project administration, J.-S.R.; funding acquisition, J.-S.R. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2018R1A5A2025286), (NRF-2020R1F1A1052496), and (NRF-2021R1A6C101A442).

Acknowledgments

We gratefully acknowledge Drug Development Research Core Center for 400 MHz NMR Spectrometer.

Conflicts of Interest

The authors declare no conflict of interest.

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Catalysts 11 01436 g001 550
Figure 1. Bioactive fused dihydroquinazolinone alkaloids.
Figure 1. Bioactive fused dihydroquinazolinone alkaloids.
Catalysts 11 01436 g001
Catalysts 11 01436 sch001 550
Scheme 1. Gold-catalyzed one-pot cascade reaction using enol/enamine-type species.
Scheme 1. Gold-catalyzed one-pot cascade reaction using enol/enamine-type species.
Catalysts 11 01436 sch001
Catalysts 11 01436 sch002 550
Scheme 2. Regioselectivity in ring closure.
Scheme 2. Regioselectivity in ring closure.
Catalysts 11 01436 sch002
Catalysts 11 01436 sch003 550
Scheme 3. Proposed mechanism.
Scheme 3. Proposed mechanism.
Catalysts 11 01436 sch003
Table
Table 1. Optimization of reaction conditions 1.
Table 1. Optimization of reaction conditions 1.
Catalysts 11 01436 i001
EntryCatalystSolventTime (h)Yield (%) 2
2a3a
1(PPh3)AuCl/AgOTftoluene5526
2(PPh3)AuCl/AgOTfCH3CN241510
3(PPh3)AuCl/AgOTfTHF2675
4(PPh3)AuCl/AgOTfCH2Cl24682
5(PPh3)AuCl/AgOTfdioxane1768
6(PPh3)AuCl/AgOTfCPME18334
7(PPh3)AuCl/AgOTfDMC4660
8(PPh3)AuCl/AgOTfDCE1800
9(PPh3)AuCl/AgNO3DCE10801
10(PPh3)AuCl/AgBF4DCE1762
11(PPh3)AuCl/AgOTsDCE1741
12(PPh3)AuCl/AgSbF6DCE244015
13(PPh3)AuClDCE24171
14AgOTfDCE24230
15(PPh3)AuNTf2DCE2787
16(XPhos)AuCl/AgOTfDCE1567
17(IPr)AuCl/AgOTfDCE3804
18(IPr)AuCl/AgNTf2DCE1684
19(IPr)AuCl/AgNO3DCE24204
20 3TfOHDCE2440
21 4(PPh3)AuCl/AgOTfDCE1760
22 5(PPh3)AuCl/AgOTfDCE1676
1 Reaction conditions: 1a (80.9 mg, 400 μmol), Au catalyst (40.0 μmol), Ag catalyst (40.0 μmol), solvent (4 mL), 4Å molecular sieve (500 mg). 2 Isolated yields. 3 Starting material was recovered. 4 A total of 5 mol% of catalyst was loaded. 5 A total of 1 mol% of catalyst was loaded.
Table
Table 2. Reaction scope 1.
Table 2. Reaction scope 1.
Catalysts 11 01436 i002
EntrySubstrateProductT (°C )Time (h)Yield (%) 2
1 Catalysts 11 01436 i003 Catalysts 11 01436 i004rt1.585
2 Catalysts 11 01436 i005 Catalysts 11 01436 i006rt390
3 Catalysts 11 01436 i007 Catalysts 11 01436 i008rt198
4 Catalysts 11 01436 i009 Catalysts 11 01436 i010602480
5 3 Catalysts 11 01436 i011 Catalysts 11 01436 i012120410
6 4 Catalysts 11 01436 i013 Catalysts 11 01436 i014120130
7 Catalysts 11 01436 i015 Catalysts 11 01436 i0161202.594
8 Catalysts 11 01436 i017 Catalysts 11 01436 i0181201.2584
9 Catalysts 11 01436 i019 Catalysts 11 01436 i0201200.357
10 Catalysts 11 01436 i021 Catalysts 11 01436 i022120161
11 5 Catalysts 11 01436 i023 Catalysts 11 01436 i024120131
12 Catalysts 11 01436 i025 Catalysts 11 01436 i026rt0.596
13 Catalysts 11 01436 i027 Catalysts 11 01436 i028rt0.597
14 Catalysts 11 01436 i029 Catalysts 11 01436 i030rt292
15 Catalysts 11 01436 i031 Catalysts 11 01436 i032rt0.597
16 Catalysts 11 01436 i033 Catalysts 11 01436 i034rt891
17 Catalysts 11 01436 i035 Catalysts 11 01436 i036rt2476
18 Catalysts 11 01436 i037 Catalysts 11 01436 i038rt372
19 Catalysts 11 01436 i039 Catalysts 11 01436 i040rt186
20 Catalysts 11 01436 i041 Catalysts 11 01436 i042601.597
1 Reaction conditions: 1b–u (400 μmol), (PPh3)AuCl (19.8 mg, 40.0 μmol, 10 mol%), Ag catalyst (10.3 mg, 40.0 μmol, 10 mol%), DCE (4 mL), 4Å molecular sieve (500 mg). 2 Isolated yields. 3 6% of ketone 3f was also isolated. 4 15% of ketone 3g was also isolated. 5 17% of ketone 3l was also isolated.
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Sun, J.; Song, Y.; Ryu, J.-S. Gold(I)-Catalyzed Tandem Synthesis of Polycyclic Dihydroquinazolinones. Catalysts 2021, 11, 1436. https://doi.org/10.3390/catal11121436

AMA Style

Sun J, Song Y, Ryu J-S. Gold(I)-Catalyzed Tandem Synthesis of Polycyclic Dihydroquinazolinones. Catalysts. 2021; 11(12):1436. https://doi.org/10.3390/catal11121436

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Sun, Jingyang, Yoona Song, and Jae-Sang Ryu. 2021. "Gold(I)-Catalyzed Tandem Synthesis of Polycyclic Dihydroquinazolinones" Catalysts 11, no. 12: 1436. https://doi.org/10.3390/catal11121436

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