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Communication

Gold(I)-Catalyzed Domino Reaction for Furopyrans Synthesis

by
Marie Ruch
,
Nicolas Brach
,
Roméric Galéa
,
Patrick Wagner
and
Gaëlle Blond
*
Laboratoire d′Innovation Thérapeutique, Université de Strasbourg, CNRS, UMR 7200, 67000 Strasbourg, France
*
Author to whom correspondence should be addressed.
Molecules 2020, 25(21), 4976; https://doi.org/10.3390/molecules25214976
Submission received: 12 October 2020 / Revised: 23 October 2020 / Accepted: 23 October 2020 / Published: 27 October 2020
(This article belongs to the Special Issue Recent Advances in Metal-Catalyzed Domino Reactions)
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Abstract

We report herein an efficient synthesis of furopyran derivatives through a gold(I)-catalyzed domino reaction. The cascade reaction starts with two regioselective cyclizations, a 5-endo-dig and a 8-endo-dig, followed with a Grob-type fragmentation and a hetero Diels–Alder. The obtained furopyran derivatives contain fused and spiro-heterocycles. During this one-pot process, four bonds and four controlled stereogenic centers including a quaternary center are formed.

Graphical Abstract

1. Introduction

Furopyrans are an important heterocyclic motif. Among furopyran scaffolds, 4H-furo[2,3-b]pyrans bearing fused bicyclic O,O-acetals are present in a number of biologically active products such as macrodasine A, xyloketal A, hyperaspidinol A and penicipyrone (Figure 1) [1,2,3,4,5].
To access a furopyran core, the hetero Diels–Alder reaction (HDA) is one of the most efficient methods, coupling a dihydrofuran with α,β-unsaturated ketone [6,7,8,9,10,11]. Particularly, gold(I)-catalyzed reactions including HDA reactions have proven to be important tools for the construction of such scaffolds. Most of the gold(I)-triggered HDA reported so far rely on the in situ generation of the diene [12,13,14] or the dienophile [15,16,17,18,19,20,21,22]. However, a HDA between diene and dienophile generated in situ by gold-catalyzed transformations remains elusive [23].
In this context, we have previously reported the synthesis of polycyclic molecules containing furopyran cores through a gold(I)-catalyzed domino reaction (Scheme 1) [24,25]. Particularly, we have described the synthesis of two classes of furopyrans, 2 and 3, starting from the same source 1 and only changing the solvent of the reaction.
Indeed, in DMF, we have prepared a series of 4H-furo[3,2-c]pyrans 2, while in 1,4-dioxane, complex 4H-furo[2,3-b]pyrans 3 have been synthesized. Concerning the formation of 3 in 1,4-dioxane, the sequence includes two cyclizations: a 5-endo-dig and a regioselective 8-endo-dig cyclization giving the 8-membered ring 8 (Scheme 2). A Grob-type fragmentation allowed the formation of the diene 9. The key step of this cascade reaction is a hetero Diels–Alder reaction (HDA) in which the formed diene 9 and the dienophile 10 are produced concomitantly. The formation of dienophile 10 comes from the protodeauration of intermediary 6. The final gold-catalyzed hydroarylation produces 3 in good yield. Continuing these works, we have decided to introduce in the reaction mixture an excess of dienophile 11. Indeed, starting with the same starting material 1 in 1,4-dioxane, intermediate 9 will react with the excess of dienophile 11 instead of dienophile 10 also present in the reaction mixture. We describe herein the synthesis of the resulting compound 4.

2. Results

2.1. Dienophiles Screening

As previously described, the conditions to obtain 3 with good yield were the use of catalyst A, in 1,4-dioxane after 20 min at 60 °C under microwave irradiation. Our first investigation was the use of these reaction conditions in the presence of an excess of dihydrofuran; we obtained good yield of 4a (64%, Entry 1, Table 1). We then decided to explore other common dienophiles [2] in order to increase the complexity of such scaffolds. The use of 4-phenylbut-3-yn-1-ol was motivated by obtaining the in situ formation of the 5-phenyl-2,3-dihydrofuran able to react as a dienophile in the reaction (entry 2) [20]. We obtained the formation of 5a with 7% yield. With dihydropyran, the conversion was total, and the protected alcohol 6 was not isolated completely purely (around 20% yield) in the middle of an unidentified product (entry 3). Surprisingly, methyl or ethyl vinyl ether gave complete conversion into a complex mixture (entries 4 and 5). The same result was observed with dihydropyrrole (entry 6), phenyl vinyl thioether (entry 7) and furan-2,5-dione (entry 8).

2.2. Scope of the Reaction

As only dihydrofuran gave a good result, we investigated the scope of the reaction using dihydrofuran with various compounds of type 1 with a range of aryls exhibiting electron-donating or -withdrawing groups at the meta or para positions (Scheme 3). Our best result was obtained with the tolyl group (4b, 80%). A para- or meta-methoxy group on the aryl ring made the reaction possible and 4c and 4d were isolated with 60% yield. Results are more disparate with halogen substitutions, where yields between 28 to 70% were obtained (4e–4i). As described previously, with ortho-substituted aryl groups, the steric hindrance hampers the reaction. Indeed, with an ortho-chloro substituted aryl, less than 5% of 4 was observed. With aryls exhibiting electron-withdrawing groups such as CF3 and NO2, yields between 34 and 60% (4j–4l) were obtained. Heteroaromatics such as thiophene and benzothiophene gave good results (4m–4n, more than 65%).

3. Conclusions

In conclusion, we have described the synthesis of new 4H-furo[2,3-b]pyrans 4 via a gold-catalyzed domino reaction. The sequence includes two regioselective cyclizations, a 5-endo-dig and a 8-endo-dig, followed with a Grob-type fragmentation and a hetero Diels–Alder reaction. A total of 14 compounds have been described and isolated, with yields ranging between 28–80%.

4. Materials and Methods

4.1. General Information

All reagents, chemicals and dry solvents were purchased from commercial sources and used without purification. When mentioned that the reaction was conducted in dry media, glassware dried for several hours at 110 °C in an oven was used. Triethylamine (Et3N) and diisopropylamine (DIPA) were distilled from KOH in an S-tube prior to each experiment in which they were involved. Reactions were monitored by TLC (thin layer silica gel chromatography) using Merck silica gel 60 F254 on aluminum sheets. TLC plates were visualized under UV light and revealed with acidic p-anisaldehyde stain or KMnO4 stain. Crude products were purified by flash column chromatography on Merck silica gel Si 60 (40–63 μm). NMR spectra were recorded in CDCl3 on a Bruker Avance III BBFO+ probe spectrometer 400 MHz for 1H analyses and 100 MHz for 13C analyses. Proton chemical shifts are reported in ppm (δ), relatively to residual CHCl3 (δ 7.26 ppm). Multiplicities are reported as follows: singlet (s), doublet (d), triplet (t), quartet (q), quintet (quint), broad singlet (bs), broad doublet (bd) combinations or multiplet (m). Coupling constant values J are given in Hz. Carbon chemical shifts are reported in ppm (δ), relative to the internal standard CDCl3 (δ 77.23 ppm). 1H and 13C NMR signals were assigned mostly on the basis of 2D-NMR (COSY, HSQC, HMBC) experiments. High resolution mass spectral analyses (HRMS) were performed using an Agilent 1200 RRLC HPLC chain and an Agilent 6520 Accurate mass QToF. Infrared spectra (IR) were recorded on a FTIR Thermo Nicollet ATR 380, Diamant Spectrometer.
All compounds 1a–1e and 1h–1n have been already described [6].

4.2. Synthesis of 1f and 1g

Anhydrous THF and distilled Et3N were mixed in a 2-necked flask under argon. The iodoaryl (1.5 eq.), PdCl2(PPh3) (0.03 eq.) and CuI (0.06 eq.) were added to the flask and this mixture was degassed with argon for 15 min. The alkyne (1 eq.) was dissolved in THF degassed with argon for 15 min and added to the 2-necked flask. The mixture was stirred overnight at room temperature (20 °C) and monitored by TLC (9/1 pent/Et2O). Once the TLC showed complete conversion of the true alkyne, the reaction mixture was filtered through a pad of Celite with CH2Cl2 as eluent and concentrated to give the crude product as a dark-brown solid. The latter was purified by flash column chromatography (98/2 pent/Et2O) to afford the pure tert-butyldimethylsilyl-protected coupling product. TBAF (1 eq.) was added to a solution of this latter protected product in THF at 0 °C. This mixture was stirred at room temperature until the TLC (9/1 pent/Et2O) showed complete conversion of the starting material. The reaction mixture was dissolved in a saturated aqueous NH4Cl solution. The aqueous phase was extracted with CH2Cl2. The gathered organic layers were dried over MgSO4, filtered and concentrated to afford the crude as a yellowish oil. The latter was purified by flash column chromatography (6/4 pent/Et2O) to afford the pure deprotected compound (1f and 1g).

4.2.1. Synthesis of 4-(2-((3-(3-bromophenyl)prop-2-yn-1-yl)oxy)phenyl)but-3-yn-1-ol 1f

Compound 1f was prepared following the general procedure using alkyne (500 mg, 1.6 mmol, 1 eq.), THF (10 mL), PdCl2(PPh3)2 (34 mg, 0.05 mmol, 0.03 eq.), CuI (18 mg, 0,1 mmol, 0.06 eq.), 3-bromoiodobenzene (679 mg, 2.4 mmol, 1.5 eq.), Et3N (4 mL) and TBAF (1.6 mL, 1.60 mmol, 1 eq.) in THF (10 mL) for the deprotection. Purification by chromatography on silica gel afforded compound 1f (81%, 499 mg, 1.405 mmol in two steps) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 7.67 (t, J = 1.7 Hz, 1H), 7.55 (ddd, J = 8.0, 2.1, 1.1 Hz, 1H), 7.50 (dd, J = 7.6, 1.7 Hz, 1H), 7.45 (dt, J = 7.8, 1.3 Hz, 1H), 7.38 (ddd, J = 8.4, 7.5, 1.8 Hz, 1H), 7.26 (t, J = 7.9 Hz, 1H), 7.15 (dd, J = 8.4, 1.1 Hz, 1H), 7.05 (td, J = 7.5, 1.0 Hz, 1H), 5.07 (s, 2H), 3.92 (q, J = 5.2 Hz, 2H), 2.84 (t, J = 6.1 Hz, 2H), 2.35 (s, 1H). 13C NMR (101 MHz, CDCl3) δ 158.3, 134.6, 133.6, 132.0, 130.5, 129.9, 129.3, 124.3, 122.2, 121.6, 113.5, 112.9, 91.3, 86.1, 85.1, 78.9, 61.2, 57.4, 24.4. HRMS ESI: Calculated for C19H15BrO2 [M + H]+ 355.0334, found 355.0311 (Diff.: 4.58 ppm).

4.2.2. 4-(2-((3-(3-chloro-4-fluorophenyl)prop-2-yn-1-yl)oxy)phenyl)but-3-yn-1-ol 1g

Compound 1g was prepared following the general procedure using alkyne (500 mg, 1.6 mmol, 1 eq.), THF (10 mL), PdCl2(PPh3)2 (34 mg, 0.05 mmol, 0.03 eq.), CuI (18 mg, 0,1 mmol, 0.06 eq.), 3-chloro-4-chloroiodobenzene (615 mg, 2.4 mmol, 1.5 eq.), Et3N (4 mL) and TBAF (0.86 mL, 0.86 mmol, 1 eq.) in THF (10 mL) for the deprotection. Purification by chromatography on silica gel afforded compound 1g (72%, 380 mg, 1.15 mmol in two steps) of as an orange oil. 1H NMR (400 MHz, CDCl3) δ 7.67 (dd, J = 7.0, 2.1 Hz, 1H), 7.60 (dd, J = 7.6, 1.7 Hz, 1H), 7.54–7.44 (m, 2H), 7.30–7.20 (m, 2H), 7.15 (td, J = 7.5, 1.0 Hz, 1H), 5.15 (s, 2H), 4.02 (t, J = 6.1 Hz, 2H), 2.94 (t, J = 6.1 Hz, 2H), 2.49 (s, 1H).13C NMR (101 MHz, CDCl3) δ 158.4 (d, J = 252.5 Hz), 158.3, 134.1, 133.6, 131.9 (d, J = 7.0 Hz), 129.3, 121.6, 121.3 (d, J = 18.0 Hz), 119.5 (d, J = 4.0 Hz), 116.8 (d, J = 21.0 Hz), 113.5, 112.9, 91.3, 85.4, 84.6, 78.9, 61.1, 57.3, 24.3. HRMS ESI: Calculated for C19H14ClFO2 [M + H]+ 329.0745, found 329.0723 (Diff.: 4.91 ppm).

4.3. General Procedure for Gold(I) Catalyzed Cascade Reactions: Preparation of 4a–n

Substrate 1 (1 eq.) and dihydrofuran (10 eq.) were placed in a 0.5–2 mL microwave reactor and dissolved in anhydrous 1,4-dioxane. Catalyst A (0.05 eq.) was added into the reactor. Once all the reagents were dissolved, the reactor was placed into the microwave for 20 min at 60 °C. The reaction mixture was filtered through a pad of Celite with CH2Cl2 as eluent. After solvent evaporation under reduced pressure, purification of the crude by flash column chromatography provided the furopyran adduct 4.

4.3.1. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-phenylpropa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4a

Compound 4a was prepared following the general procedure using compound 1a (20 mg, 0.072 mmol, 1 eq.), dihydrofuran (51 mg, 0.72 mmol, 10 eq.) and catalyst A (3 mg, 0.004 mmol, 0.05 eq.) in 1,4-dioxane (0.4 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4a (64%, 16 mg, 0.046 mmol) as an amorphous white solid. 1H NMR (400 MHz, CDCl3) δ 7.28–7.24 (m, 1H), 7.23–7.11 (m, 5H), 7.11–7.05 (m, 1H), 6.89 (td, J = 7.5, 1.2 Hz, 1H), 6.62 (dd, J = 8.1, 1.2 Hz, 1H), 5.31 (d, J = 5.6 Hz, 1H), 4.81 (dd, J = 11.7, 1.3 Hz, 1H), 4.42 (d, J = 11.7 Hz, 1H), 4.33 (td, J = 8.4, 3.8 Hz, 1H), 4.10 (td, J = 8.4, 7.3 Hz, 1H), 3.87–3.73 (m, 2H), 3.48–3.37 (m, 1H), 2.75 (td, J = 9.4, 5.6 Hz, 1H), 2.48 (dtd, J = 12.8, 7.3, 3.8 Hz, 1H), 2.30 (dq, J = 12.7, 8.5 Hz, 1H), 2.13–1.99 (m, 1H), 1.70 (dtd, J = 12.9, 9.6, 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.3, 153.0, 137.0, 129.0, 128.4, 127.5, 126.8, 126.5, 125.2, 120.8, 116.0, 105.1, 101.6, 85.0, 78.3, 67.8, 67.0, 49.7, 49.6, 33.3, 27.0. HRMS ESI: Calculated for C23H23O3 [M + H]+ 347.1647, found 347.1642 (Diff.: 0.31 ppm).

4.3.2. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(p-tolyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4b

Compound 4b was prepared following the general procedure using compound 1b (50 mg, 0.172 mmol, 1 eq.), dihydrofuran (120 mg, 1.72 mmol, 10 eq.) and catalyst A (7 mg, 0.009 mmol, 0.05 eq.) in 1,4-dioxane (0.4 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4b (80%, 50 mg, 0.138 mmol) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 7.24 (dd, J = 7.7, 1.6 Hz, 1H), 7.10 (td, J = 7.7, 1.7 Hz, 1H), 7.05 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 6.90 (dd, J = 7.5, 1.2 Hz, 1H), 6.64 (dd, J = 8.1, 1.2 Hz, 1H), 5.25 (d, J = 5.7 Hz, 1H), 4.76 (d, J = 11.5 Hz, 1H), 4.32 (td, J = 8.8, 3.6 Hz, 2H), 4.09 (td, J = 8.7, 7.2 Hz, 1H), 3.88–3.70 (m, 2H), 3.38 (dd, J = 8.9, 7.1 Hz, 1H), 2.72 (td, J = 9.5, 5.6 Hz, 1H), 2.44 (dtd, J = 12.7, 7.1, 3.5 Hz, 1H), 2.38–2.22 (m, 4H), 2.15–1.99 (m, 1H), 1.70 (dq, J = 12.8, 8.9 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.1, 153.0, 136.5, 134.1, 129.1, 129.0, 127.6, 126.3, 125.2, 120.7, 116.0, 104.6, 101.5, 85.0, 78.1, 67.7, 67.0, 49.9, 49.8, 33.3, 27.0, 21.1. HRMS ESI: Calculated for C24H25O3 [M + H]+ 361.1804, found 361.1793 (Diff.: 1.59 ppm).

4.3.3. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(3-methoxyphenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4c

Compound 4c was prepared following the general procedure using compound 1c (51 mg, 0.167 mmol, 1 eq.), dihydrofuran (117 mg, 1.67 mmol, 10 eq.) and catalyst A (6 mg, 0.008 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4c (61%, 39 mg, 0.102 mmol) as an amorphous yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.29–7.20 (m, 1H), 7.16–7.05 (m, 2H), 6.88 (td, J = 7.5, 1.2 Hz, 1H), 6.78 (dt, J = 7.9, 1.2 Hz, 1H), 6.70–6.59 (m, 3H), 5.35 (d, J = 5.7 Hz, 1H), 4.81 (dd, J = 11.7, 1.4 Hz, 1H), 4.52–4.37 (m, 1H), 4.31 (td, J = 8.4, 3.9 Hz, 1H), 4.08 (td, J = 8.4, 7.4 Hz, 1H), 3.94–3.65 (m, 5H), 3.47–3.26 (m, 1H), 2.75 (td, J = 9.5, 5.7 Hz, 1H), 2.46 (dtd, J = 12.7, 7.3, 3.9 Hz, 1H), 2.28 (dq, J = 12.6, 8.4 Hz, 1H), 2.05 (dddd, J = 12.9, 9.2, 7.2, 4.8 Hz, 1H), 1.69 (ddt, J = 12.9, 9.9, 8.7 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.2, 159.6, 153.0, 138.5, 129.2, 129.0, 127.5, 125.1, 120.7, 118.8, 116.0, 112.4, 112.3, 105.2, 101.6, 84.9, 78.3, 67.8, 66.9, 55.2, 49.6, 49.6, 33.3, 27.0. HRMS ESI: Calculated for C24H25O4 [M + H]+ 377.1753, found 377.1750 (Diff.: −0.74 ppm).

4.3.4. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(4-methoxyphenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4d

Compound 4d was prepared following the general procedure using compound 1d (49 mg, 0.160 mmol, 1 eq.), dihydrofuran (112 mg, 1.60 mmol, 10 eq.) and catalyst A (7 mg, 0.009 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4d (60%, 37 mg, 0.098 mmol) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.24 (dd, J = 7.6, 1.7 Hz, 1H), 7.12–7.03 (m, 3H), 6.88 (td, J = 7.5, 1.2 Hz, 1H), 6.79–6.70 (m, 2H), 6.63 (dd, J = 8.0, 1.2 Hz, 1H), 5.30 (d, J = 5.7 Hz, 1H), 4.78 (dd, J = 11.4, 1.3 Hz, 1H), 4.38 (dd, J = 11.4, 1.0 Hz, 1H), 4.32 (td, J = 8.4, 3.8 Hz, 1H), 4.08 (td, J = 8.5, 7.3 Hz, 1H), 3.85–3.72 (m, 6H), 3.40–3.32 (m, 1H), 2.74 (td, J = 9.5, 5.7 Hz, 1H), 2.46 (dtd, J = 12.8, 7.2, 3.7 Hz, 1H), 2.28 (dq, J = 12.8, 8.5 Hz, 1H), 2.06 (dddd, J = 12.9, 9.3, 7.3, 4.7 Hz, 1H), 1.85–1.66 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 208.9, 158.5, 152.9, 129.1, 128.9, 127.4, 127.4, 125.1, 120.6, 115.8, 113.7, 104.5, 101.4, 84.9, 78.0, 67.6, 66.8, 55.2, 49.8, 49.6, 33.1, 26.9. HRMS ESI: Calculated for C24H24NaO4 [M + Na]+ 399.1572, found 399.1551 (Diff.: 4.13 ppm).

4.3.5. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(3-fluorophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4e

Compound 4e was prepared following the general procedure using compound 1e (50 mg, 0.170 mmol, 1 eq.), dihydrofuran (119 mg, 1.70 mmol, 10 eq.) and catalyst A (7 mg, 0.009 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4e (65%, 41 mg, 0.11 mmol) as orange oil. 1H NMR (400 MHz, CDCl3) δ 7.28–7.22 (m, 1H), 7.18–7.05 (m, 2H), 6.96–6.86 (m, 2H), 6.85–6.75 (m, 2H), 6.60 (dd, J = 8.1, 1.2 Hz, 1H), 5.40 (d, J = 5.8 Hz, 1H), 4.87 (dd, J = 12.0, 1.3 Hz, 1H), 4.52 (d, J = 11.9 Hz, 1H), 4.31 (td, J = 8.4, 4.3 Hz, 1H), 4.09 (q, J = 8.1 Hz, 1H), 3.89–3.75 (m, 2H), 3.39 (dd, J = 8.1, 6.8 Hz, 1H), 2.79 (td, J = 9.4, 5.8 Hz, 1H), 2.50 (dtd, J = 12.8, 7.5, 4.2 Hz, 1H), 2.38–2.24 (m, 1H), 2.06 (dddd, J = 12.9, 9.3, 6.6, 5.5 Hz, 1H), 1.83–1.64 (m, 1H).13C NMR (101 MHz, CDCl3) δ 209.2, 162.8 (d, J = 244.9 Hz), 152.9, 139.4 (d, J = 7.6 Hz), 129.6 (d, J = 8.4 Hz), 129.1, 127.4, 125.2, 121.8 (d, J = 2.7 Hz), 120.9, 116.1, 113.6 (d, J = 21.2 Hz), 113.5 (d, J = 23.2 Hz), 104.9, 101.6, 84.9, 78.8, 67.8, 66.8, 49.5, 49.1, 33.1, 27.0. 19F NMR (376 MHz, CDCl3) δ −113.54–−113.72 (m). HRMS ESI: Calculated for C23H22FO3 [M + H]+ 365.1553, found 365.1546 (Diff.: 0.51 ppm).

4.3.6. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(3-bromophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4f

Compound 4f was prepared following the general procedure using compound 1f (53 mg, 0.149 mmol, 1 eq.), dihydrofuran (104 mg, 1.49 mmol, 10 eq.) and catalyst A (7 mg, 0.009 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4f (70%, 45 mg, 0.104 mmol) as an amorphous yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.24 (dd, J = 7.6, 1.7 Hz, 1H), 7.22–7.18 (m, 1H), 7.12 (q, J = 1.4 Hz, 1H), 7.10–7.00 (m, 3H), 6.89 (td, J = 7.5, 1.2 Hz, 1H), 6.57 (dd, J = 8.1, 1.2 Hz, 1H), 5.43 (d, J = 5.8 Hz, 1H), 4.89 (dd, J = 11.9, 1.5 Hz, 1H), 4.58 (dd, J = 12.0, 1.1 Hz, 1H), 4.29 (td, J = 8.4, 4.6 Hz, 1H), 3.78 (dd, J = 8.4, 6.1 Hz, 2H), 3.37 (tt, J = 7.2, 1.4 Hz, 1H), 2.79 (td, J = 9.4, 5.8 Hz, 1H), 2.55–2.42 (m, 1H), 2.27 (dtd, J = 12.8, 8.2, 7.0 Hz, 1H), 2.12–1.98 (m, 1H), 1.69 (ddt, J = 12.9, 9.7, 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.1, 152.9, 139.1, 129.6 (3C), 129.1, 127.2, 125.1, 124.8, 122.4, 121.0, 116.1, 105.0, 101.6, 84.9, 78.9, 67.8, 66.7, 49.4, 48.9, 32.9, 26.9. HRMS ESI: Calculated for C23H21BrNaO3 [M + Na]+ 447.0572, found 447.0567 (Diff.: −0.49 ppm).

4.3.7. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(3-chloro-4-fluorophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4g

Compound 4g was prepared following the general procedure using compound 1g (52 mg, 0.16 mmol, 1 eq.), dihydrofuran (112 mg, 1.6 mmol, 10 eq.) and catalyst A (8 mg, 0.010 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4g (44%, 28 mg, 0.070 mmol) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.27–7.21 (m, 1H), 7.05 (ddd, J = 8.1, 7.3, 1.7 Hz, 1H), 7.00–6.85 (m, 4H), 6.55 (dd, J = 8.0, 1.2 Hz, 1H), 5.48 (d, J = 5.9 Hz, 1H), 4.92 (dt, J = 11.9, 1.2 Hz, 1H), 4.66 (dt, J = 11.8, 1.2 Hz, 1H), 4.28 (td, J = 8.4, 5.1 Hz, 1H), 4.07 (td, J = 8.2, 7.1 Hz, 1H), 3.82–3.75 (m, 2H), 3.35 (ddt, J = 7.7, 6.2, 1.5 Hz, 1H), 2.82 (td, J = 9.4, 5.9 Hz, 1H), 2.52 (dtd, J = 12.8, 7.8, 5.1 Hz, 1H), 2.28 (dddd, J = 13.2, 8.4, 7.2, 6.1 Hz, 1H), 2.11–1.98 (m, 1H), 1.68 (ddt, J = 12.9, 9.5, 8.3 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 208.9, 156.9 (d, J = 256.6 Hz), 152.8, 134.0 (d, J = 3.3 Hz), 129.1, 128.7, 127.1, 125.9 (d, J = 7.1 Hz), 125.3, 121.1, 120.6 (d, J = 17.8 Hz), 116.1, 116.0 (d, J = 21.1 Hz), 104.8, 101.7, 84.8, 79.1, 67.9, 66.5, 49.2, 48.9, 32.8, 26.9. HRMS ESI: Calculated for C23H21ClFO3 [M + H]+ 399.1163, found 399.1165 (Diff.: −0.61 ppm).

4.3.8. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(4-bromo-3-fluorophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4h

Compound 4h was prepared following the general procedure using compound 1h (50 mg, 0.152 mmol, 1 eq.), dihydrofuran (106 mg, 1.52 mmol, 10 eq.) and catalyst A (6 mg, 0.008 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4h (46%, 24 mg, 0.070 mmol) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.32 (dd, J = 8.6, 7.3 Hz, 1H), 7.24 (dd, J = 7.5, 1.8 Hz, 1H), 7.07 (ddd, J = 8.1, 7.3, 1.7 Hz, 1H), 6.88 (td, J = 7.5, 1.2 Hz, 1H), 6.84–6.75 (m, 2H), 6.58 (dd, J = 8.1, 1.2 Hz, 1H), 5.45 (d, J = 5.9 Hz, 1H), 4.91 (dd, J = 12.1, 1.4 Hz, 1H), 4.59 (dd, J = 12.2, 1.0 Hz, 1H), 4.30 (td, J = 8.4, 4.7 Hz, 1H), 4.08 (q, J = 7.9 Hz, 1H), 3.78 (dd, J = 8.4, 6.1 Hz, 2H), 3.35 (t, J = 7.1 Hz, 1H), 2.81 (td, J = 9.3, 5.9 Hz, 1H), 2.51 (dtd, J = 12.5, 7.7, 4.7 Hz, 1H), 2.27 (dq, J = 12.9, 7.6 Hz, 1H), 2.05 (ddt, J = 12.7, 9.4, 6.1 Hz, 1H), 1.69 (dq, J = 13.0, 8.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.1, 158.8 (d, J = 246.4 Hz), 152.9, 138.6 (d, J = 6.9 Hz), 132.9 (d, J = 1.0 Hz), 129.2, 127.3, 125.4, 122.9 (d, J = 3.2 Hz), 121.1, 116.2, 114.5 (d, J = 23.5 Hz), 106.8 (d, J = 21.2 Hz), 104.86 (d, J = 2.2 Hz), 101.7, 84.9, 79.3, 67.9, 66.6, 49.4, 48.7, 32.9, 27.0. HRMS ESI: Calculated for C23H20BrFNaO3 [M + Na]+ 465.0478, found 465.0464 (Diff.: 0.65 ppm).

4.3.9. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(4-chlorophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4i

Compound 4i was prepared following the general procedure using compound 1i (50 mg, 0.161 mmol, 1 eq.), dihydrofuran (113 mg, 1.61 mmol, 10 eq.) and catalyst A (8 mg, 0.010 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4i (28%, 17 mg, 0.045 mmol) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.25 (dd, J = 7.6, 1.7 Hz, 1H), 7.16–7.11 (m, 2H), 7.09–7.01 (m, 3H), 6.88 (td, J = 7.5, 1.2 Hz, 1H), 6.59 (dd, J = 8.1, 1.2 Hz, 1H), 5.38 (d, J = 5.8 Hz, 1H), 4.86 (dd, J = 11.9, 1.4 Hz, 1H), 4.51 (dd, J = 11.9, 1.1 Hz, 1H), 4.31 (td, J = 8.4, 4.3 Hz, 1H), 4.08 (q, J = 8.0 Hz, 1H), 3.84–3.73 (m, 2H), 3.37 (tt, J = 7.3, 1.3 Hz, 1H), 2.78 (td, J = 9.4, 5.8 Hz, 1H), 2.50 (dtd, J = 12.7, 7.5, 4.3 Hz, 1H), 2.28 (dtd, J = 12.8, 8.3, 7.4 Hz, 1H), 2.05 (dddd, J = 12.9, 9.3, 6.7, 5.4 Hz, 1H), 1.79–1.60 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 209.1, 152.9, 135.4, 132.4, 129.1, 128.4, 127.7, 127.4, 125.3, 121.0, 116.2, 104.9, 101.6, 84.9, 78.7, 67.9, 66.8, 49.5, 49.1, 33.1, 27.0. HRMS ESI: Calculated for C23H22ClO3 [M + H]+ 381.1257, found 381.1255 (Diff.: −0.64 ppm).

4.3.10. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(4-(trifluoromethyl)phenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4j

Compound 4j was prepared following the general procedure using compound 1j (50 mg, 0.145 mmol, 1 eq.), dihydrofuran (102 mg, 1.45 mmol, 10 eq.) and catalyst A (6 mg, 0.007 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4j (44%, 26 mg, 0.064 mmol) as an amorphous yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.42–7.36 (m, 2H), 7.30–7.23 (m, 1H), 7.19 (d, J = 8.1 Hz, 2H), 7.03 (ddd, J = 8.0, 7.3, 1.7 Hz, 1H), 6.87 (td, J = 7.5, 1.2 Hz, 1H), 6.53 (dd, J = 8.1, 1.2 Hz, 1H), 5.43 (d, J = 6.0 Hz, 1H), 5.02–4.82 (m, 1H), 4.62 (d, J = 12.1 Hz, 1H), 4.31 (td, J = 8.4, 4.7 Hz, 1H), 4.10 (q, J = 8.0 Hz, 1H), 3.91–3.68 (m, 2H), 3.57–3.35 (m, 1H), 2.82 (td, J = 9.4, 5.9 Hz, 1H), 2.54 (dtd, J = 12.6, 7.7, 4.7 Hz, 1H), 2.44–2.23 (m, 1H), 2.13–1.97 (m, 1H), 1.69 (ddt, J = 12.9, 9.5, 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.6, 152.9, 140.7, 129.2, 128.7 (q, J = 32.4 Hz), 127.3, 126.6, 125.4, 125.1 (q, J = 3.8 Hz), 124.4 (q, J = 273.7 Hz), 121.1, 116.3, 105.3, 101.7, 85.0, 79.0, 67.9, 66.7, 49.4, 48.7, 33.0, 27.0. 19F NMR (376 MHz, CDCl3) δ–62.48 (s). HRMS ESI: Calculated for C24H21F3NaO3 [M + Na]+ 437.1340, found 437.1336 (Diff.: −0.31 ppm).

4.3.11. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(4-nitrophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4k

Compound 4k was prepared following the general procedure using compound 1k (50 mg, 0.205 mmol, 1 eq.), dihydrofuran (167 mg, 2.05 mmol, 10 eq.) and catalyst A (9 mg, 0.012 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4k (60%, 48 mg, 0.12 mmol) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 9.0 Hz, 2H), 7.26 (dd, J = 7.5, 1.7 Hz, 1H), 7.20 (d, J = 8.9 Hz, 2H), 7.06–6.97 (m, 1H), 6.86 (td, J = 7.5, 1.2 Hz, 1H), 6.49 (dd, J = 8.0, 1.2 Hz, 1H), 5.52 (d, J = 6.1 Hz, 1H), 5.04 (dd, J = 12.7, 1.6 Hz, 1H), 4.79 (dd, J = 12.7, 1.2 Hz, 1H), 4.31 (td, J = 8.5, 5.3 Hz, 1H), 4.09 (td, J = 8.4, 6.9 Hz, 1H), 3.77 (ddd, J = 8.5, 6.2, 3.4 Hz, 2H), 3.63–3.45 (m, 1H), 2.88 (td, J = 9.3, 6.1 Hz, 1H), 2.59 (dtd, J = 13.1, 8.0, 5.3 Hz, 1H), 2.40–2.28 (m, 1H), 2.04 (dddd, J = 12.6, 9.4, 7.2, 5.2 Hz, 1H), 1.69 (dq, J = 13.1, 8.6 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 210.0, 152.7, 146.2, 143.7, 129.2, 127.2, 126.9, 125.6, 123.3, 121.3, 116.3, 105.8, 101.8, 84.8, 79.6, 67.9, 66.4, 49.1, 47.9, 32.7, 26.9. HRMS ESI: Calculated for C23H21NNaO5 [M + Na]+ 414.1317, found 414.1309 (Diff.: 0.35 ppm).

4.3.12. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(3-nitrophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4l

Compound 4l was prepared following the general procedure using compound 1l (51 mg, 0.159 mmol, 1 eq.), dihydrofuran (111 mg, 1.59 mmol, 10 eq.) and catalyst A (8 mg, 0.010 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4l (34%, 21 mg, 0.054 mmol) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 7.90 (ddd, J = 8.0, 2.3, 1.2 Hz, 1H), 7.81 (t, J = 2.0 Hz, 1H), 7.34 (dt, J = 7.8, 1.5 Hz, 1H), 7.31–7.23 (m, 2H), 7.04–6.92 (m, 1H), 6.87 (td, J = 7.4, 1.3 Hz, 1H), 6.42 (dd, J = 8.0, 1.3 Hz, 1H), 5.53 (d, J = 6.0 Hz, 1H), 5.03 (dd, J = 12.2, 1.7 Hz, 1H), 4.83 (dd, J = 12.3, 1.4 Hz, 1H), 4.30 (td, J = 8.4, 5.5 Hz, 1H), 4.10 (td, J = 8.4, 6.8 Hz, 1H), 3.84–3.70 (m, 2H), 3.51 (ddt, J = 7.2, 5.4, 1.6 Hz, 1H), 2.88 (td, J = 9.3, 6.0 Hz, 1H), 2.68–2.50 (m, 1H), 2.43–2.28 (m, 1H), 2.04 (dddd, J = 12.7, 9.4, 7.3, 5.0 Hz, 1H), 1.76–1.60 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 209.2, 152.8, 148.1, 138.7, 132.3, 129.1, 128.8, 127.1, 125.6, 125.5, 121.4, 121.3, 116.2, 105.5, 101.8, 84.9, 79.7, 68.0, 66.5, 49.1, 48.3, 32.6, 26.9. HRMS ESI: Calculated for C23H21NNaO5 [M + Na]+ 414.1317, found 414.1296 (Diff.: 4.40 ppm).

4.3.13. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(thiophen-2-yl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4m

Compound 4m was prepared following the general procedure using compound 1m (50 mg, 0.177 mmol, 1 eq.), dihydrofuran (124 mg, 1.77 mmol, 10 eq.) and catalyst A (7 mg, 0.09 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4m (65%, 41 mg, 0.117 mmol) as an amorphous yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.24 (dd, J = 7.6, 1.7 Hz, 1H), 7.15–7.05 (m, 2H), 6.93–6.79 (m, 3H), 6.66 (dd, J = 8.1, 1.2 Hz, 1H), 5.54 (d, J = 5.7 Hz, 1H), 4.89 (d, J = 12.3 Hz, 1H), 4.48 (dd, J = 12.3, 0.9 Hz, 1H), 4.30 (td, J = 8.5, 3.9 Hz, 1H), 4.14–4.00 (m, 1H), 3.92–3.75 (m, 2H), 3.42–3.25 (m, 1H), 2.83 (td, J = 9.5, 5.7 Hz, 1H), 2.47 (dtd, J = 12.8, 7.4, 3.9 Hz, 1H), 2.25 (dq, J = 12.8, 8.4 Hz, 1H), 2.08 (dddd, J = 12.8, 9.2, 7.2, 4.9 Hz, 1H), 1.72 (ddt, J = 12.9, 9.8, 8.5 Hz, 1H).13C NMR (101 MHz, CDCl3) δ 208.4, 153.0, 141.3, 129.1, 127.5, 127.3, 124.9, 124.5, 123.0, 120.8, 116.1, 101.7, 100.8, 84.9, 79.5, 67.8, 66.8, 51.1, 49.6, 32.9, 27.1. HRMS ESI: Calculated for C21H21SO3 [M + H]+ 353.1211, found 353.1196 (Diff.: 2.77 ppm).

4.3.14. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(benzo[b]thiophen-2-yl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4n

Compound 4i was prepared following the general procedure using compound 1i (50 mg, 0.150 mmol, 1 eq.), dihydrofuran (105 mg, 1.50 mmol, 10 eq.) and catalyst A (6 mg, 0.008 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4i (68%, 41 mg, 0.102 mmol) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 7.7–7.6 (m, 2H), 7.3–7.2 (m, 3H), 7.2–7.0 (m, 2H), 6.9 (td, J = 7.5, 1.2 Hz, 1H), 6.7 (dd, J = 8.0, 1.2 Hz, 1H), 5.6 (d, J = 5.8 Hz, 1H), 5.0 (dt, J = 12.8, 1.1 Hz, 1H), 4.5 (dt, J = 12.8, 1.0 Hz, 1H), 4.3 (td, J = 8.5, 3.6 Hz, 1H), 4.1 (td, J = 8.6, 7.5 Hz, 1H), 4.0–3.7 (m, 2H), 3.4 (dd, J = 8.4, 7.1 Hz, 1H), 2.9 (td, J = 9.4, 5.8 Hz, 1H), 2.5 (dtd, J = 12.8, 7.3, 3.6 Hz, 1H), 2.4–2.2 (m, 1H), 2.2–2.0 (m, 1H), 1.7 (ddt, J = 12.9, 9.7, 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.3, 153.0, 141.9, 140.4, 139.4, 129.2, 127.5, 125.2, 124.3, 124.2, 123.3, 122.0, 121.0, 119.2, 116.3, 101.9, 101.4, 85.0, 80.0, 67.8, 66.8, 50.1, 49.7, 33.0, 27.2. HRMS ESI: Calculated for C25H23SO3 [M + H]+ 403.1368, found 403.1354 (Diff.: 1.64 ppm).
Procedures for the synthesis of the substrates and the products and full characterization of final products can be found in the Supplementary Materials.

Supplementary Materials

The supplementary materials are available online.

Author Contributions

Conceptualization, G.B.; methodology, M.R., N.B. and R.G.; formal analysis, M.R., N.B. and R.G.; writing—original draft preparation, G.B.; writing—review and editing, G.B.; supervision, G.B. and P.W.; project administration, G.B. All authors have read and agreed to the published version of the manuscript.

Funding

University of Strasbourg Institute for Advanced Study (USIAS), the Chemistry of Complex Systems LabEx and the Frontier Research in Chemistry Foundation.

Acknowledgments

The authors gratefully acknowledge the support of the University of Strasbourg Institute for Advanced Study (USIAS), the Chemistry of Complex Systems LabEx and the Frontier Research in Chemistry Foundation. We sincerely thank the leading committee of the Laboratoire d′Innovation Thérapeutique (UMR 7200) for its technical support.

Conflicts of Interest

The authors declare no conflict of interest.

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Sample Availability: Samples of the compounds 4a–4n and 5a are available from the authors.
Molecules 25 04976 g001
Figure 1. Representative natural products with 4H-furo[2,3-b]pyran scaffolds.
Figure 1. Representative natural products with 4H-furo[2,3-b]pyran scaffolds.
Molecules 25 04976 g001
Molecules 25 04976 sch001
Scheme 1. Gold(I)-catalyzed cascade reaction with 1.
Scheme 1. Gold(I)-catalyzed cascade reaction with 1.
Molecules 25 04976 sch001
Molecules 25 04976 sch002
Scheme 2. Proposed mechanism.
Scheme 2. Proposed mechanism.
Molecules 25 04976 sch002
Molecules 25 04976 sch003
Scheme 3. Scope of the reaction.
Scheme 3. Scope of the reaction.
Molecules 25 04976 sch003
Table 1. Optimization of the reaction conditions. 1
Table 1. Optimization of the reaction conditions. 1
EntryDienophileProductYield (%)
1Molecules 25 04976 i001Molecules 25 04976 i0024a 64%
2Molecules 25 04976 i003Molecules 25 04976 i0045a 7%
3Molecules 25 04976 i005Molecules 25 04976 i0066 20%
4Molecules 25 04976 i007CM 2-
5Molecules 25 04976 i008CM 2-
6Molecules 25 04976 i009CM 2-
7Molecules 25 04976 i010CM 2-
8Molecules 25 04976 i011CM 2-
1 The reactions were performed by adding Cat. A (5 mol%) to a solution of 1a (1equiv.) and dienophile (10 equiv.) in 1,4-dioxane (0.145 M). 2 CM: Complex Mixture.
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Ruch, M.; Brach, N.; Galéa, R.; Wagner, P.; Blond, G. Gold(I)-Catalyzed Domino Reaction for Furopyrans Synthesis. Molecules 2020, 25, 4976. https://doi.org/10.3390/molecules25214976

AMA Style

Ruch M, Brach N, Galéa R, Wagner P, Blond G. Gold(I)-Catalyzed Domino Reaction for Furopyrans Synthesis. Molecules. 2020; 25(21):4976. https://doi.org/10.3390/molecules25214976

Chicago/Turabian Style

Ruch, Marie, Nicolas Brach, Roméric Galéa, Patrick Wagner, and Gaëlle Blond. 2020. "Gold(I)-Catalyzed Domino Reaction for Furopyrans Synthesis" Molecules 25, no. 21: 4976. https://doi.org/10.3390/molecules25214976

APA Style

Ruch, M., Brach, N., Galéa, R., Wagner, P., & Blond, G. (2020). Gold(I)-Catalyzed Domino Reaction for Furopyrans Synthesis. Molecules, 25(21), 4976. https://doi.org/10.3390/molecules25214976

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