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Article

Convergent Synthesis of Polysubstituted Furans via Catalytic Phosphine Mediated Multicomponent Reactions

by
Xia Fan
1,
Rongshun Chen
2,*,
Jie Han
1 and
Zhengjie He
1,*
1
The State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
2
Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, China
*
Authors to whom correspondence should be addressed.
Molecules 2019, 24(24), 4595; https://doi.org/10.3390/molecules24244595
Submission received: 15 November 2019 / Revised: 10 December 2019 / Accepted: 13 December 2019 / Published: 16 December 2019
(This article belongs to the Section Organic Chemistry)
Browse Figures
Versions Notes

Abstract

:
Tri- or tetrasubstituted furans have been prepared from terminal activated olefins and acyl chlorides or anhydrides by a multicomponental convergent synthesis mode. Instead of stoichiometric nBu3P, only catalytic nBu3P or nBu3P=O is needed to furnish the furans in modest to excellent yields with a good functional group tolerance under the aid of reducing agent silane. This synthetic method features a silane-driven catalytic intramolecular Wittig reaction as a key annulation step and represents the first successful application of catalytic Wittig reaction in multicomponent cascade reaction.

1. Introduction

The Wittig reaction [1,2,3,4] provides a powerful tool for convenient construction of carbon-carbon double bonds in synthetic chemistry. Despite the popularity of this reaction, some major drawbacks are associated with the formation of stoichiometric phosphine oxides as by-products. The troublesome purification of the by-products [5] makes them valueless on an industrial scale [6,7,8]. Also, most well-designed phosphines, especially chiral phosphine reagents [9,10,11,12,13,14,15], are very expensive and high cost hampers their applications in asymmetric Wittig reaction [16,17,18,19,20,21,22,23,24,25]. In this context, it is highly desired to develop a catalytic version of phosphine-mediated Wittig reaction by in-situ recycling by-product phosphine oxide under the aid of a reducing agent. However, it is a challenging task to reuse phosphine oxides to effect a catalytic Wittig reaction [26,27,28]. First, phosphine oxides are not generally easy to be reduced into the corresponding phosphines at a substantially fast rate under mild conditions; second, the employed reducing agent should be safe for other functional groups of the substrates [29,30]. Consequently, although many new methods for reduction of phosphine oxides have emerged by using reducing agents such as DIBAL-H [31,32], LiAlH4 [33,34], boron compounds [35,36,37,38], and others [39,40,41,42,43,44,45], applicable ones for catalytic Wittig reactions remain rare. Recently, silanes have been recognized as powerful reducing agents for in-situ deoxygenation of phosphine oxides with good functional tolerance after a series of successful applications of silanes in the transformation of a stoichiometric phosphine-mediated reaction into a catalytic one [46,47,48,49,50,51,52]. In 2009, O’Brien et al. [53] developed the first catalytic Wittig reaction for efficient synthesis of alkenes in moderate to high yields by using silanes such as diphenyl silane or trimethoxysilane to reuse in-situ by-product phosphine oxide [54,55,56]. In 2012, Beller and coworkers realized efficient and chemoselective reduction of tertiary and secondary phosphine oxides to their corresponding phosphines by using silanes under the aid of catalytic copper complexes [57] or specific Brønsted acids [58]. Under the reported conditions, various reducible functional groups such as ketones, aldehydes, olefins, nitriles, and esters were well tolerated. Based on these encouraging findings, a number of important stoichiometric phosphine-involved reactions, including (aza-)Wittig [59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75], Mitsunobu [76,77,78], Staudinger [79,80,81,82,83,84], Appel [85,86], Cadogan [87], and others [88,89,90,91,92,93] have been successfully developed into the catalytic phosphine mediated ones.
Multicomponent reactions (MCRs) [94,95,96] have attracted much interest from organic chemists in recent years as a highly efficient synthetic strategy. In 2012, our group [97] realized a stoichiometric phosphine-mediated pseudo-three-component reaction between terminal activated olefins and acyl chlorides or anhydrides, leading to a convenient and convergent synthesis of tetra-substituted furans in moderate to excellent yields. The highly functionalized furan product was formed from one molecule of activated olefin and two or three molecules of acyl chloride or anhydride under the mediation of nBu3P through a multiple domino sequence consisting of C-acylation, O-acylation, and intramolecular Wittig reaction (Scheme 1). A concomitant by-product nBu3P=O was also formed [97]. Considering its high efficiency in synthesis of tetra-substituted furans and its characteristic of the multicomponent cascade reaction, we were interested in exploring a catalytic version of this reaction by using silanes as reducing agents. As mentioned above, although silanes have been successfully used as reducing agents in a series of catalytic versions of important phosphine-mediated reactions like the Wittig reaction [53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93], this silane-reduction strategy has never been applied to a stoichiometric phosphine mediated multicomponent cascade reaction before. Furthermore, the addition of reducing agent silane will certainly result in an increased complexity of a multiple domino reaction sequence. Herein we report the relevant results from such challenging studies.

2. Results and Discussion

Our investigation started with a model reaction between tert-butyl acrylate 1a and 3-chlorobenzoyl chloride 2a (Table 1). Under the similar conditions of our previous work [97], tert-butyl acrylate (0.5 mmol) and 3-chlorobenzoyl chloride (1.8 mmol) were added to THF (2.0 mL) under N2, followed by addition of catalytic nBu3P (0.1 mmol), NEt3 (2.7 mmol) and Ph2SiH2 (0.6 mmol), the resulting mixture was stirred at room temperature for 24 h. The desired product 3aa was obtained, but only in 11% yield (entry 1). The reaction was then conducted at 60 °C and the yield of 3aa was not substantially improved (entry 2). Although only a trace amount of the product was observed in a PhSiH3 mediated reaction run at room temperature in toluene (entry 3), to our delight, tetra-substituted furan 3aa was obtained in 74% yield when the temperature was raised to 110 °C in refluxing toluene (entry 4). Other silanes such as Ph2SiH2, (MeO)3SiH, polymethylhydrosiloxane (PMHS) and Ph3SiH were effective but offered inferior results (entries 5‒9); SiHCl3 were ineffective at all (entry 10). The loading amount of PhSiH3 was studied and a decreased loading (0.4 mmol) could also smoothly offer a yield of 84% (entries 11‒13). A lower reaction temperature (80 °C) resulted in a decreased yield (entry 14). Solvents like dioxane, xylene, and DMF only gave inferior results and acetonitrile was detrimental to the reaction (entries 15‒18). A lowered loading amount of nBu3P (0.05 mmol, 10 mol%) was investigated, only giving the product in a moderate yield (entry 19). Other phosphines such as PPh3 and Ph2PMe were totally ineffective as reported before [97]. Thus, the optimized conditions were established as those shown in Table 1, entry 12.
Under the optimized conditions, the substrate scope of alkenes 1 and acyl chlorides 2 were further examined (Table 2). Gratifyingly, reducible functional groups such as ketone, acyl chloride, olefin, nitro, cyano, and ester were all well tolerated in this multicomponent reaction, and moderate to excellent yields were generally obtained when different substrates were employed (Table 2). When tert-butyl acrylate 1a was employed, a series of substituted benzoyl chlorides 2, except o-chlorobenzoyl chloride 2c and 4-nitrobenzoyl chloride 2f, readily afforded the corresponding tetra-substituted furans 3 in good yields (entries 1‒6). Hetero-aryl acyl chloride like 2-thiofuroyl chloride (2g) was also effective in this transformation, furnishing the corresponding tetrasubstituted furan 3ag in moderate yield (entry 7). Methyl, ethyl, n-butyl and benzyl acrylates (1b–e), acrylonitrile 1f were all good candidates for this reaction and the expected products were readily delivered in moderate to good yields (entries 8‒17). Aliphatic anhydride 2a’ was also found to be a suitable substrate, albeit giving a lower yield (entry 18).
To further test the generality of the reaction, di-substituted alkene 1g and 1h were also studied (Scheme 2). We found that α,β-unsaturated ketones were well compatible under standard conditions, affording the corresponding tetra-substituted furans in satisfactory yields with different benzoyl chlorides (Scheme 2).
To our surprise, methyl vinyl ketone (MVK) 1i was also effective under the catalytic conditions, furnishing the corresponding tri-substituted furans 3id and 3ie in fair yields in the reactions with benzoyl chlorides (Scheme 3). It is worthy to note that, in our previous work [97], the more reactive alkene MVK 1i failed to deliver the expected furans in appreciable yields under the mediation of stoichiometric nBu3P. Presumably, under the silane-driven catalytic conditions, the instant concentration of nBu3P would be kept at a relatively low level in the reaction mixture. The low concentration of nBu3P may diminish the possible side reactions of the highly reactive olefin like 1i.
In order to gain more insights about the reaction, some control experiments were conducted (Scheme 4). In a 31P NMR tracking experiment (a sealed capillary containing C6D6 was used for field locking and shimming), a signal at δ −32.4 ppm was observed which was identified as nBu3P when nBu3P=O (0.1 mmol) and silane PhSiH3 (0.4 mmol) were mixed with or without NEt3 (0.4 mmol) in toluene in an NMR tube under N2 for 24 h (for details, see Supporting Information). These results provided direct evidence for the regeneration of the nBu3P catalyst. As expected, tetra-substituted furan 3aa was readily obtained in 51% isolated yield when nBu3P=O (20 mol%) was used instead of nBu3P. In contrast, an increased loading of nBu3P=O (100 mol%) only brought in a modestly improved yield (58%). The silane PhSiH3 alone could not effect the domino reaction. These results indicated that nBu3P=O was the equivalent catalyst of nBu3P in the presence of silane PhSiH3. It is noticeable that nBu3P=O was inactive as a catalyst in Lin’s report [68].
Based on the results of this work and previous reports [59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,97], a multiple domino process is proposed to rationalize the formation of tetra-substituted furans 3 (Scheme 5, left). The catalytic cycle starts with the nucleophilic addition of nBu3P to an activate alkene 1 like acrylates, the resulting intermediate undergoes a C-acylation reaction with acyl chloride 2 to give a phosphonium enolate A. The phosphorus ylide B, generated through the O-acylation reaction of intermediate A with acyl chloride 2 in the presence of NEt3, engages in another C-acylation reaction to deliver an ylide C under the aid of base NEt3. Finally, a polysubstituted furan is delivered through an intramolecular Wittig reaction of ylide C with the release of nBu3P=O. The phosphine oxide nBu3P=O is then in-situ reduced by silane PhSiH3 into nBu3P, which enters the next catalytic cycle. Regarding the formation of the tri-substituted furans 3id and 3ie from MVK 1i, a similar triple domino sequence of C-acylation/O-acylation/intramolecular Wittig reaction presumably occurs (Scheme 5, right).

3. Experimental Section

Unless otherwise noted, all reactions were carried out in a nitrogen atmosphere under anhydrous conditions. Solvents were purified prior to use according to standard procedures. 1H and 13C NMR spectra were recorded in CDCl3 with tetramethylsilane (TMS) as the internal standard. Column chromatography was performed on silica gel (200–300 mesh) using a mixture of petroleum ether (60–90 °C)/ethyl acetate as the eluant. 2-Acyl acrylates 1g–h were prepared according to the reported procedure [98].
Typical procedure for synthesis of highly functionalized furans 3: Under a N2 atmosphere, to a solution of activated olefins 1a–1i (0.5 mmol), acylation agent 2 (1.8 mmol) in toluene (2.0 mL) were sequentially added nBu3P (25 μL, 0.1 mmol), Et3N (2.7 mmol) and silane (0.4 mmol) by means of microsyringe. The resulting reaction mixture was stirred at 110 °C for 24 h. After completion of the reaction as monitored by TLC, water (10 mL) was added. The mixture was extracted with CH2Cl2 (3 × 10 mL). The combined organic layer was washed with saturated brine (10 mL) and dried over anhydrous sodium sulfate. After filtration, the solvent was removed on a rotary evaporator under reduced pressure, and the residue was subjected to column chromatographic isolation on silica gel (eluted with petroleum ether/ ethyl acetate (40:1–20:1) to give furans 3.
3aa–3de, 3fb–3he are known compounds in our previous report [97]. NMR spectra of compounds 3 are available in Supplementary Materials.
3aa, 221 mg, 84% yield; as a yellow solid; m.p. 110–111 °C; 1H-NMR (400 MHz, CDCl3) δ 8.04 (d, J = 0.7 Hz, 1H), 7.98 (t, J = 1.7 Hz, 1H), 7.97–7.92 (m, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.67 (d, J = 1.7 Hz, 1H), 7.60–7.53 (m, 1H), 7.48–7.38 (m, 4H), 7.31–7.22 (m, 2H), 1.23 (s, 9H).
3ab, 199 mg, 75% yield; as a yellow solid; m.p. 198–199 °C; 1H-NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.7 Hz, 2H), 7.92 (d, J = 8.6 Hz, 2H), 7.53 (d, J = 8.7 Hz, 2H), 7.46 (dd, J = 8.7, 6.7 Hz, 4H), 7.30 (d, J = 8.7 Hz, 2H), 1.19 (s, 9H).
3ac, 87 mg, 33% yield; as a yellow solid; m.p. 118–120 °C; 1H-NMR (400 MHz, CDCl3) δ 7.66 (dd, J = 7.6, 1.5 Hz, 1H), 7.60 (dd, J = 7.4, 1.9 Hz, 1H), 7.53–7.46 (m, 2H), 7.42–7.34 (m, 2H), 7.34–7.27 (m, 3H), 7.27–7.24 (m, 1H), 7.23–7.16 (m, 2H), 1.22 (s, 9H).
3ad, 149 mg, 70% yield; as a white solid; m.p. 181–183 °C; 1H-NMR (400 MHz, CDCl3) δ 8.14–7.94 (m, 4H), 7.69–7.62 (m, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.53–7.41 (m, 5H), 7.37–7.26 (m, 3H), 1.16 (s, 9H).
3ae, 210 mg, 90% yield; as a white solid; m.p. 160–162 °C; 1H-NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.2 Hz, 2H), 7.79 (d, J = 8.1 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.15 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.1 Hz, 2H), 2.27 (s, 3H), 2.25 (s, 3H), 2.15 (s, 3H), 1.06 (s, 9H).
3af, 102 mg, 37% yield; as a yellow solid; m.p. 178–180 °C; 1H-NMR (400 MHz, CDCl3) δ 8.37 (t, J = 9.6 Hz, 4H), 8.30 (d, J = 8.7 Hz, 2H), 8.23 (d, J = 8.6 Hz, 2H), 8.18 (d, J = 8.5 Hz, 2H), 7.79 (d, J = 8.6 Hz, 2H), 1.22 (s, 9H).
3ag, 101 mg, 46% yield; as a oil; 1H-NMR (400 MHz, CDCl3) δ 8.10 (dd, J = 3.8, 1.0 Hz, 1H), 7.69 (dd, J = 4.9, 1.0 Hz, 1H), 7.61–7.59 (m, 1H), 7.48 (dd, J = 5.0, 1.0 Hz, 1H), 7.45 (dd, J = 3.7, 1.0 Hz, 1H), 7.32 (dd, J = 5.0, 1.0 Hz, 1H), 7.15 (dd, J = 5.0, 3.9 Hz, 1H), 7.09 (dd, J = 4.8, 3.9 Hz, 1H), 7.02 (dd, J = 5.0, 3.8 Hz, 1H), 1.25 (s, 9H).
3bb,196 mg, 81% yield; as a yellow solid; m.p. 185–186 °C; 1H-NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.51–7.41 (m, 4H), 7.31 (d, J = 8.4 Hz, 2H), 3.50 (s, 3H).
3be, 190 mg, 84% yield; as a yellow solid; m.p. 185–186 °C; 1H-NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.0 Hz, 2H), 7.85 (d, J = 7.9 Hz, 2H), 7.53 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 7.9 Hz, 2H), 7.22 (d, J = 7.8 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 3.46 (s, 3H), 2.41 (s, 3H), 2.37 (s, 3H), 2.29 (s, 3H).
3cb, 178 mg, 71% yield; as a white solid; m.p. 177–178 °C; 1H-NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 8.3 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.45 (t, J = 9.2 Hz, 4H), 7.31 (d, J = 8.4 Hz, 2H), 4.00 (q, J = 7.1 Hz, 2H), 0.93 (t, J = 7.1 Hz, 3H).
3ce, 195 mg, 84% yield; as a white solid; m.p. 134–136 °C; 1H-NMR (400 MHz, CDCl3) δ 7.95 (d, J = 7.9 Hz, 2H), 7.88 (d, J = 7.8 Hz, 2H), 7.53 (d, J = 7.9 Hz, 2H), 7.28 (d, J = 7.9 Hz, 2H), 7.23 (d, J = 7.9 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 3.97 (q, J = 7.0 Hz, 2H), 2.41 (s, 3H), 2.38 (s, 3H), 2.29 (s, 3H), 0.90 (t, J = 7.1 Hz, 3H).
3db, 224 mg, 85% yield, as a yellow solid; m.p. 142–143 °C; 1H-NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.6 Hz, 2H), 7.90 (d, J = 8.5 Hz, 2H), 7.53 (d, J = 8.6 Hz, 2H), 7.44 (t, J = 8.6 Hz, 4H), 7.29 (d, J = 8.6 Hz, 2H), 3.96 (t, J = 6.6 Hz, 2H), 1.28–1.23 (m, 2H), 1.09–1.07 (m, 2H), 0.77 (t, J = 7.3 Hz, 3H).
3de, 193 mg, 83% yield, as a white solid; m.p. 120–121 °C; 1H-NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.1 Hz, 2H), 7.88 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.1 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 8.1 Hz, 2H), 3.93 (t, J = 6.5 Hz, 2H), 2.40 (s, 3H), 2.37 (s, 3H), 2.28 (s, 3H), 1.35–1.15 (m, 2H), 1.07–1.05 (m, 2H), 0.74 (t, J = 7.3 Hz, 3H).
3ed, 200 mg, 87% yield, as a white solid; m.p. 124–126 °C; 1H-NMR (400 MHz, CDCl3) δ 8.07 (dd, J = 6.5, 2.7 Hz, 2H), 7.92 (d, J = 7.6 Hz, 2H), 7.68 (d, J = 7.9 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.53–7.47 (m, 2H), 7.41 (t, J = 7.7 Hz, 2H), 7.38–7.31 (m, 3H), 7.30–7.22 (m, 2H), 7.05 (d, J = 7.1 Hz, 2H), 5.00 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 192.2, 162.2, 156.3, 150.1, 137.3, 134.6, 133.4, 129.9, 129.3, 128.9, 128.8, 128.7, 128.6, 128.5, 128.3, 128.2, 128.2, 128.0, 125.9, 121.8, 115.1, 66.7. HRMS-ESI calcd. for C31H23O4 [M + H]+ 459.1591; found 459.1593.
3fb, 85 mg, 38% yield, as a yellow solid; m.p. 181–182 °C; 1H-NMR (400 MHz, CDCl3) 8.03 (d, J = 8.6 Hz, 2H), 7.81 (d, J = 8.5 Hz, 2H), 7.52 (dd, J = 8.3, 6.2 Hz, 4H), 7.41 (d, J = 8.5 Hz, 2H), 7.33 (d, J = 8.6 Hz, 2H).
3fd, 100 mg, 57% yield, as a white solid; m.p. 152–154 °C; 1H-NMR (400 MHz, CDCl3) δ 8.18–8.07 (m, 2H), 7.88 (d, J = 7.3 Hz, 2H), 7.62–7.48 (m, 6H), 7.39 (t, J = 7.7 Hz, 2H), 7.32 (t, J = 6.4 Hz, 3H).
3fe, 85 mg, 44% yield, as a yellow solid; m.p. 165–167 °C; 1H-NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 2H), 7.80 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 7.9 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 2.42 (s, 3H), 2.37 (s, 3H), 2.31 (s, 3H).
3aa’, 32 mg, 27% yield; as a oil; 1H-NMR (400 MHz, CDCl3) δ 2.46 (s, 3H), 2.43 (s, 3H), 2.34 (s, 3H), 1.55 (s, 9H).
3gb, 133 mg, 57% yield; as a white solid; m.p. 135–137 °C; 1H-NMR (400 MHz, CDCl3) δ 8.06–8.00 (m, 2H), 7.94–7.89 (m, 2H), 7.59–7.53 (m, 2H), 7.52–7.46 (m, 3H), 7.46–7.42 (m, 2H), 7.33–7.28 (m, 2H), 4.00 (q, J = 7.1 Hz, 2H), 0.94 (t, J = 7.1 Hz, 3H).
3ge, 117 mg, 55% yield; as a white solid; m.p. 128–130 °C; 1H-NMR (400 MHz, CDCl3) δ 8.09–8.02 (m, 2H), 7.88 (d, J = 8.2 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H), 7.51–7.41 (m, 3H), 7.24 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 8.1 Hz, 2H), 3.97 (q, J = 7.1 Hz, 2H), 2.40 (s, 3H), 2.31 (s, 3H), 0.90 (t, J = 7.1 Hz, 3H).
3hb, 149 mg, 60% yield; as a yellow solid; m.p. 150–151 °C; 1H-NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.9 Hz, 2H), 7.91 (d, J = 8.5 Hz, 2H), 7.55 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H), 7.28 (d, J = 8.7 Hz, 2H), 7.00 (d, J = 8.9 Hz, 2H), 3.99 (q, J = 7.1 Hz, 2H), 3.87 (s, 3H), 0.92 (t, J = 7.1 Hz, 3H).
3he, 150 mg, 66% yield; as a white solid; m.p. 132–133 °C; 1H-NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.6 Hz, 2H), 7.87 (d, J = 7.8 Hz, 2H), 7.52 (d, J = 7.9 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 8.1 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 3.96 (q, J = 7.1 Hz, 2H), 3.87 (s, 3H), 2.40 (s, 3H), 2.30 (s, 3H), 0.89 (t, J = 7.1 Hz, 3H).
3id, 38 mg, 29% yield; as a yellow oil; 1H-NMR (400 MHz, CDCl3) δ 7.77–7.73 (m, 2H), 7.58 (dd, J = 7.8, 1.7 Hz, 2H), 7.44–7.35 (m, 2H), 7.28 (dd, J = 13.2, 5.4 Hz, 2H), 7.21–7.15 (m, 2H), 6.21 (d, J = 0.8 Hz, 1H), 2.31 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 191.9, 154.5, 151.1, 138.2, 132.6, 130.0, 129.7, 128.6, 128.2, 128.1(overlap), 127.2, 121.7, 109.7, 13.4; HRMS-ESI calcd. for C18H15O2 [M + H]+ 263.1067; found 263.1071.
3ie, 55 mg, 38% yield; as a yellow oil; 1H-NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.1 Hz, 2H), 7.58 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 8.1 Hz, 2H), 6.24 (d, J = 0.8 Hz, 1H), 2.38 (s, 6H), 2.31 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 191.7, 154.3, 150.6, 143.4, 138.5, 135.7, 129.8, 128.9 (overlap), 127.3, 127.0, 121.3, 109.7, 21.6, 21.3, 13.4; HRMS-ESI calcd. for C20H19O2 [M + H]+ 291.1380; found 291.1383.

4. Conclusions

In conclusion, a convergent synthetic method for tri- or tetra-substituted furans has been developed by catalytic phosphine mediated multicomponental cascade reactions. Instead of stoichiometric nBu3P, only catalytic nBu3P or nBu3P=O is needed to deliver the furans in modest to excellent yields. A broad scope of substrates, bearing various reducible functional groups including ketone, acyl chloride, olefin, nitro, cyano, and ester, are all well tolerated in the presence of reducing agent silane. This synthetic method features a silane-driven catalytic intramolecular Wittig reaction as a key step and represents the first successful application of catalytic Wittig reaction in a multicomponent cascade reaction. Future efforts in our laboratory will be directed toward exploring the asymmetric reactions involving catalytic chiral phosphine mediated Wittig reaction, the results of which will be reported in due course.

Supplementary Materials

The supplementary materials are available online.

Author Contributions

R.C. and Z.H. conceived and designed the experiments; X.F. performed the experiments; J.H. checked and analyzed the data; R.C. wrote the paper; Z.H. revised the manuscript.

Funding

This research was funded by the National Natural Science Foundation of China (Grant Nos. 21472096, 21801134, J1103306).

Acknowledgments

Financial support from the National Natural Science Foundation of China (Grant Nos. 21472096, 21801134, J1103306) is gratefully acknowledged.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Byrne, P.A.; Gilheany, D.G. The modern interpretation of the Wittig reaction mechanism. Chem. Soc. Rev. 2013, 42, 6670–6696. [Google Scholar] [CrossRef] [Green Version]
  2. Chelucci, G. Synthesis and Metal-Catalyzed Reactions of gem-Dihalovinyl Systems. Chem. Rev. 2012, 112, 1344–1462. [Google Scholar] [CrossRef]
  3. Perin, G.; Lenardão, E.J.; Jacob, R.G.; Panatieri, R.B. Synthesis of Vinyl Selenides. Chem. Rev. 2009, 109, 1277–1301. [Google Scholar] [CrossRef]
  4. Flynn, A.B.; Ogilvie, W.W. Stereocontrolled Synthesis of Tetrasubstituted Olefins. Chem. Rev. 2007, 107, 4698–4745. [Google Scholar] [CrossRef]
  5. Batesky, D.C.; Goldfogel, M.J.; Weix, D.J. Removal of Triphenylphosphine Oxide by Precipitation with Zinc Chloride in Polar Solvents. J. Org. Chem. 2017, 82, 9931–9936. [Google Scholar] [CrossRef] [Green Version]
  6. Bergbreiter, D.E.; Yang, Y.-C.; Hobbs, C.E. Polyisobutylene-Supported Phosphines as Recyclable and Regenerable Catalysts and Reagents. J. Org. Chem. 2011, 76, 6912–6917. [Google Scholar] [CrossRef]
  7. Constable, D.J.C.; Dunn, P.J.; Hayler, J.D.; Humphrey, G.R.; Leazer, J.J.L.; Linderman, R.J.; Lorenz, K.; Manley, J.; Pearlman, B.A.; Wells, A.; et al. Key green chemistry research areas-a perspective from pharmaceutical manufacturers. Green Chem. 2007, 9, 411–420. [Google Scholar] [CrossRef]
  8. Dandapani, S.; Curran, D.P. Separation-Friendly Mitsunobu Reactions: A Microcosm of Recent Developments in Separation Strategies. Chem. Eur. J. 2004, 10, 3130–3138. [Google Scholar] [CrossRef]
  9. Dutartre, M.; Bayardon, J.; Juge, S. Applications and stereoselective syntheses of P-chirogenic phosphorus compounds. Chem. Soc. Rev. 2016, 45, 5771–5794. [Google Scholar] [CrossRef]
  10. Wang, Z.; Xu, X.; Kwon, O. Phosphine catalysis of allenes with electrophiles. Chem. Soc. Rev. 2014, 43, 2927–2940. [Google Scholar] [CrossRef] [Green Version]
  11. Wei, Y.; Shi, M. Applications of Chiral Phosphine-Based Organocatalysts in Catalytic Asymmetric Reactions. Chem. Asian J. 2014, 9, 2720–2734. [Google Scholar] [CrossRef] [PubMed]
  12. Marinetti, A.; Voituriez, A. Enantioselective Phosphine Organocatalysis. Synlett 2010, 174–194. [Google Scholar] [CrossRef]
  13. Glueck, D.S. Catalytic asymmetric synthesis of chiral phosphanes. Chem. Eur. J. 2008, 14, 7108–7117. [Google Scholar] [CrossRef] [PubMed]
  14. Li, Y.-M.; Kwong, F.-Y.; Yu, W.-Y.; Chan, A.S.C. Recent advances in developing new axially chiral phosphine ligands for asymmetric catalysis. Coord. Chem. Rev. 2007, 251, 2119–2144. [Google Scholar] [CrossRef]
  15. Pietrusiewicz, K.M.; Zablocka, M. Preparation of Scalemic P-Chiral Phosphines and Their Derivatives. Chem. Rev. 1994, 94, 1375–1411. [Google Scholar] [CrossRef]
  16. Rein, T.; Pedersen, T.M. Palladium-catalyzed reaction of olefins with PhI(OAc)2-TBAB system: An efficient and highly selective bisfunctionalization strategy. Synthesis 2002, 2002, 579–594. [Google Scholar] [CrossRef]
  17. Rein, T.; Reiser, O. Recent advances in asymmetric Wittig-type reactions. Acta Chem. Scand. 1996, 50, 369–379. [Google Scholar] [CrossRef]
  18. Zhang, K.; Lu, L.-Q.; Yao, S.; Chen, J.-R.; Shi, D.-Q.; Xiao, W.-J. Enantioconvergent Copper Catalysis: In Situ Generation of the Chiral Phosphorus Ylide and Its Wittig Reactions. J. Am. Chem. Soc. 2017, 139, 12847–12854. [Google Scholar] [CrossRef]
  19. Wong, G.W.; Landis, C.R. Iterative Asymmetric Hydroformylation/Wittig Olefination Sequence. Angew. Chem. Int. Ed. 2013, 52, 1564–1567. [Google Scholar] [CrossRef]
  20. Enders, D.; Grossmann, A.; Gieraths, B.; Duezdemir, M.; Merkens, C. Organocatalytic One-Pot Asymmetric Synthesis of 4H,5H-Pyrano[2,3-c]pyrazoles. Org. Lett. 2012, 14, 4254–4257. [Google Scholar] [CrossRef]
  21. Lin, A.; Wang, J.; Mao, H.; Ge, H.; Tan, R.; Zhu, C.; Cheng, Y. Organocatalytic Asymmetric Michael-Type/Wittig Reaction of Phosphorus Ylides: Synthesis of Chiral α-Methylene-δ-Ketoesters. Org. Lett. 2011, 13, 4176–4179. [Google Scholar] [CrossRef] [PubMed]
  22. Gramigna, L.; Duce, S.; Filippini, G.; Fochi, M.; Franchini, M.C.; Bernardi, L. Organocatalytic asymmetric Wittig reactions: Generation of enantioenriched axially chiral olefins breaking a symmetry plane. Synlett 2011, 2745–2749. [Google Scholar] [CrossRef]
  23. Ye, L.-W.; Wang, S.-B.; Wang, Q.-G.; Sun, X.-L.; Tang, Y.; Zhou, Y.-G. Asymmetric tandem Michael addition-ylide olefination reaction for the synthesis of optically active cyclohexa-1,3-diene derivatives. Chem. Commun. 2009, 3092–3094. [Google Scholar] [CrossRef] [PubMed]
  24. Liu, Y.-k.; Ma, C.; Jiang, K.; Liu, T.-Y.; Chen, Y.-C. Asymmetric Tandem Michael Addition-Wittig Reaction to Cyclohexenone Annulation. Org. Lett. 2009, 11, 2848–2851. [Google Scholar] [CrossRef] [PubMed]
  25. Hong, B.-C.; Jan, R.-H.; Tsai, C.-W.; Nimje, R.Y.; Liao, J.-H.; Lee, G.-H. Organocatalytic Enantioselective Cascade Michael-Michael-Wittig Reactions of Phosphorus Ylides: One-Pot Synthesis of the all-cis Trisubstituted Cyclohexenecarboxylates via the [1 + 2 + 3] Annulation. Org. Lett. 2009, 11, 5246–5249. [Google Scholar] [CrossRef] [PubMed]
  26. Voituriez, A.; Saleh, N. From phosphine-promoted to phosphine-catalyzed reactions by in situ phosphine oxide reduction. Tetrahedron Lett. 2016, 57, 4443–4451. [Google Scholar] [CrossRef]
  27. Xu, S.; Tang, Y. Catalytic approaches to stoichiometric phosphine-mediated organic reactions. Lett. Org. Chem. 2014, 11, 524–533. [Google Scholar] [CrossRef]
  28. Van Kalkeren, H.A.; van Delft, F.L.; Rutjes, F.P.J.T. Organophosphorus Catalysis to Bypass Phosphine Oxide Waste. ChemSusChem 2013, 6, 1615–1624. [Google Scholar] [CrossRef]
  29. Zhao, Q.; Curran, D.P.; Malacria, M.; Fensterbank, L.; Goddard, J.-P.; Lacôte, E. N-Heterocyclic Carbene-Catalyzed Hydrosilylation of Styryl and Propargylic Alcohols with Dihydrosilanes. Chem. Eur. J. 2011, 17, 9911–9914. [Google Scholar] [CrossRef]
  30. Quin, L.D.; Caster, K.C.; Kisalus, J.C.; Mesch, K.A. Bridged ring systems containing phosphorus: Structural influences on the stereochemistry of silane reductions of P-oxides and on carbon-13 and phosphorus-31 NMR properties of phosphines. J. Am. Chem. Soc. 1984, 106, 7021–7032. [Google Scholar] [CrossRef]
  31. Busacca, C.A.; Raju, R.; Grinberg, N.; Haddad, N.; James-Jones, P.; Lee, H.; Lorenz, J.C.; Saha, A.; Senanayake, C.H. Reduction of Tertiary Phosphine Oxides with DIBAL-H. J. Org. Chem. 2008, 73, 1524–1531. [Google Scholar] [CrossRef] [PubMed]
  32. Busacca, C.A.; Lorenz, J.C.; Grinberg, N.; Haddad, N.; Hrapchak, M.; Latli, B.; Lee, H.; Sabila, P.; Saha, A.; Sarvestani, M.; et al. A Superior Method for the Reduction of Secondary Phosphine Oxides. Org. Lett. 2005, 7, 4277–4280. [Google Scholar] [CrossRef] [PubMed]
  33. Imamoto, T.; Kikuchi, S.-i.; Miura, T.; Wada, Y. Stereospecific Reduction of Phosphine Oxides to Phosphines by the Use of a Methylation Reagent and Lithium Aluminum Hydride. Org. Lett. 2001, 3, 87–90. [Google Scholar] [CrossRef] [PubMed]
  34. Henson, P.D.; Naumann, K.; Mislow, K. Stereomutation of phosphine oxide by lithium aluminum hydride. J. Amer. Chem. Soc. 1969, 91, 5645–5646. [Google Scholar] [CrossRef]
  35. Sowa, S.; Stankevic, M.; Flis, A.; Pietrusiewicz, K.M. Reduction of Tertiary Phosphine Oxides by BH3 Assisted by Neighboring Activating Groups. Synthesis 2018, 50, 2106–2118. [Google Scholar]
  36. Provis-Evans, C.B.; Emanuelsson, E.A.C.; Webster, R.L. Rapid Metal-Free Formation of Free Phosphines from Phosphine Oxides. Adv. Synth. Catal. 2018, 360, 3999–4004. [Google Scholar] [CrossRef]
  37. Elias, J.S.; Costentin, C.; Nocera, D.G. Direct Electrochemical P(V) to P(III) Reduction of Phosphine Oxide Facilitated by Triaryl Borates. J. Am. Chem. Soc. 2018, 140, 13711–13718. [Google Scholar] [CrossRef]
  38. Mehta, M.; Garcia de la Arada, I.; Perez, M.; Porwal, D.; Oestreich, M.; Stephan, D.W. Metal-Free Phosphine Oxide Reductions Catalyzed by B(C6F5)3 and Electrophilic Fluorophosphonium Cations. Organometallics 2016, 35, 1030–1035. [Google Scholar] [CrossRef]
  39. Stepen, A.J.; Bursch, M.; Grimme, S.; Stephan, D.W.; Paradies, J. Electrophilic Phosphonium Cation-Mediated Phosphane Oxide Reduction Using Oxalyl Chloride and Hydrogen. Angew. Chem. Int. Ed. 2018, 57, 15253–15256. [Google Scholar] [CrossRef]
  40. Li, P.; Wischert, R.; Metivier, P. Mild Reduction of Phosphine Oxides with Phosphites To Access Phosphines. Angew. Chem. Int. Ed. 2017, 56, 15989–15992. [Google Scholar] [CrossRef]
  41. Kuroboshi, M.; Kita, T.; Aono, A.; Katagiri, T.; Kikuchi, S.; Yamane, S.; Kawakubo, H.; Tanaka, H. Reduction of phosphine oxides to the corresponding phosphine derivatives in Mg/Me3SiCl/DMI system. Tetrahedron Lett. 2015, 56, 918–920. [Google Scholar] [CrossRef]
  42. Pehlivan, L.; Metay, E.; Delbrayelle, D.; Mignani, G.; Lemaire, M. Reduction of phosphine oxides to phosphines with the InBr3/TMDS system. Tetrahedron 2012, 68, 3151–3155. [Google Scholar] [CrossRef]
  43. Rajendran, K.V.; Gilheany, D.G. Simple unprecedented conversion of phosphine oxides and sulfides to phosphine boranes using sodium borohydride. Chem. Commun. 2012, 48, 817–819. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Kawakubo, H.; Kuroboshi, M.; Yano, T.; Kobayashi, K.; Kamenoue, S.; Akagi, T.; Tanaka, H. Electroreduction of triphenylphosphine oxide to triphenylphosphine in the presence of chlorotrimethylsilane. Synthesis 2011, 4091–4098. [Google Scholar]
  45. Yano, T.; Kuroboshi, M.; Tanaka, H. Electroreduction of triphenylphosphine dichloride and the efficient one-pot reductive conversion of phosphine oxide to triphenylphosphine. Tetrahedron Lett. 2010, 51, 698–701. [Google Scholar] [CrossRef]
  46. Longwitz, L.; Werner, T. Recent advances in catalytic Wittig-type reactions based on P(III)/P(V) redox cycling. Pure Appl. Chem. 2019, 91, 95–102. [Google Scholar] [CrossRef] [Green Version]
  47. Podyacheva, E.; Kuchuk, E.; Chusov, D. Reduction of phosphine oxides to phosphines. Tetrahedron Lett. 2019, 60, 575–582. [Google Scholar] [CrossRef]
  48. Karanam, P.; Reddy, G.M.; Lin, W. Strategic Exploitation of the Wittig Reaction: Facile Synthesis of Heteroaromatics and Multifunctional Olefins. Synlett 2018, 29, 2608–2622. [Google Scholar]
  49. Kovacs, T.; Keglevich, G. The Reduction of Tertiary Phosphine Oxides by Silanes. Curr. Org. Chem. 2017, 21, 569–585. [Google Scholar] [CrossRef] [Green Version]
  50. Kovacs, T.; Keglevich, G. The deoxygenation of phosphine oxides under green chemical conditions. Phosphorus Sulfur Silicon Relat. Elem. 2016, 191, 359–366. [Google Scholar] [CrossRef]
  51. Lao, Z.; Toy, P.H. Catalytic Wittig and aza-Wittig reactions. Beilstein J. Org. Chem. 2016, 12, 2577–2587. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  52. Herault, D.; Nguyen, D.H.; Nuel, D.; Buono, G. Reduction of secondary and tertiary phosphine oxides to phosphines. Chem. Soc. Rev. 2015, 44, 2508–2528. [Google Scholar] [CrossRef] [PubMed]
  53. O’Brien, C.J.; Tellez, J.L.; Nixon, Z.S.; Kang, L.J.; Carter, A.L.; Kunkel, S.R.; Przeworski, K.C.; Chass, G.A. Recycling the Waste: The Development of a Catalytic Wittig Reaction. Angew. Chem. Int. Ed. 2009, 48, 6836–6839. [Google Scholar] [CrossRef] [PubMed]
  54. O’Brien, C.J.; Lavigne, F.; Coyle, E.E.; Holohan, A.J.; Doonan, B.J. Breaking the Ring through a Room Temperature Catalytic Wittig Reaction. Chem. Eur. J. 2013, 19, 5854–5858. [Google Scholar]
  55. O’Brien, C.J.; Nixon, Z.S.; Holohan, A.J.; Kunkel, S.R.; Tellez, J.L.; Doonan, B.J.; Coyle, E.E.; Lavigne, F.; Kang, L.J.; Przeworski, K.C. Part I: The Development of the Catalytic Wittig Reaction. Chem. Eur. J. 2013, 19, 15281–15289. [Google Scholar] [CrossRef]
  56. Coyle, E.E.; Doonan, B.J.; Holohan, A.J.; Walsh, K.A.; Lavigne, F.; Krenske, E.H.; O’Brien, C.J. Catalytic Wittig Reactions of Semi- and Nonstabilized Ylides Enabled by Ylide Tuning. Angew. Chem. Int. Ed. 2014, 53, 12907–12911. [Google Scholar] [CrossRef]
  57. Li, Y.; Das, S.; Zhou, S.; Junge, K.; Beller, M. General and Selective Copper-Catalyzed Reduction of Tertiary and Secondary Phosphine Oxides: Convenient Synthesis of Phosphines. J. Am. Chem. Soc. 2012, 134, 9727–9732. [Google Scholar] [CrossRef]
  58. Li, Y.; Lu, L.-Q.; Das, S.; Pisiewicz, S.; Junge, K.; Beller, M. Highly Chemoselective Metal-Free Reduction of Phosphine Oxides to Phosphines. J. Am. Chem. Soc. 2012, 134, 18325–18329. [Google Scholar] [CrossRef]
  59. Cai, L.; Zhang, K.; Chen, S.; Lepage, R.J.; Houk, K.N.; Krenske, E.H.; Kwon, O. Catalytic Asymmetric Staudinger-aza-Wittig Reaction for the Synthesis of Heterocyclic Amines. J. Am. Chem. Soc. 2019, 141, 9537–9542. [Google Scholar] [CrossRef]
  60. Longwitz, L.; Spannenberg, A.; Werner, T. Phosphetane Oxides as Redox Cycling Catalysts in the Catalytic Wittig Reaction at Room Temperature. ACS Catal. 2019, 9, 9237–9244. [Google Scholar] [CrossRef]
  61. Lorton, C.; Castanheiro, T.; Voituriez, A. Catalytic and Asymmetric Process via PIII/PV=O Redox Cycling: Access to (Trifluoromethyl)cyclobutenes via a Michael Addition/Wittig Olefination Reaction. J. Am. Chem. Soc. 2019, 141, 10142–10147. [Google Scholar] [CrossRef]
  62. Fianchini, M.; Maseras, F. DFT characterization of the mechanism for Staudinger/aza-Wittig tandem organocatalysis. Tetrahedron 2019, 75, 1852–1859. [Google Scholar] [CrossRef]
  63. Han, X.; Saleh, N.; Retailleau, P.; Voituriez, A. Phosphine-Catalyzed Reaction between 2-Aminobenzaldehydes and Dialkyl Acetylenedicarboxylates: Synthesis of 1,2-Dihydroquinoline Derivatives and Toward the Development of an Olefination Reaction. Org. Lett. 2018, 20, 4584–4588. [Google Scholar] [CrossRef] [PubMed]
  64. Wang, L.; Sun, M.; Ding, M.-W. Catalytic Intramolecular Wittig Reaction Based on a Phosphine/Phosphine Oxide Catalytic Cycle for the Synthesis of Heterocycles. Eur. J. Org. Chem. 2017, 2568–2578. [Google Scholar] [CrossRef]
  65. Wang, L.; Xie, Y.-B.; Huang, N.-Y.; Yan, J.-Y.; Hu, W.-M.; Liu, M.-G.; Ding, M.-W. Catalytic aza-Wittig Reaction of Acid Anhydride for the Synthesis of 4H-Benzo[d][1,3]oxazin-4-ones and 4-Benzylidene-2-aryloxazol-5(4H)-ones. ACS Catal. 2016, 6, 4010–4016. [Google Scholar] [CrossRef]
  66. Saleh, N.; Voituriez, A. Synthesis of 9H-Pyrrolo[1,2-a]indole and 3H-Pyrrolizine Derivatives via a Phosphine-Catalyzed Umpolung Addition/Intramolecular Wittig Reaction. J. Org. Chem. 2016, 81, 4371–4377. [Google Scholar] [CrossRef]
  67. Schirmer, M.-L.; Adomeit, S.; Spannenberg, A.; Werner, T. Novel Base-Free Catalytic Wittig Reaction for the Synthesis of Highly Functionalized Alkenes. Chem. Eur. J. 2016, 22, 2458–2465. [Google Scholar] [CrossRef]
  68. Lee, C.-J.; Chang, T.-H.; Yu, J.-K.; Madhusudhan Reddy, G.; Hsiao, M.-Y.; Lin, W. Synthesis of Functionalized Furans via Chemoselective Reduction/Wittig Reaction Using Catalytic Triethylamine and Phosphine. Org. Lett. 2016, 18, 3758–3761. [Google Scholar] [CrossRef]
  69. Schirmer, M.-L.; Adomeit, S.; Werner, T. First Base-Free Catalytic Wittig Reaction. Org. Lett. 2015, 17, 3078–3081. [Google Scholar] [CrossRef]
  70. Tsai, Y.-L.; Lin, W. Synthesis of Multifunctional Alkenes from Substituted Acrylates and Aldehydes via Phosphine-Catalyzed Wittig Reaction. Asian J. Org. Chem. 2015, 4, 1040–1043. [Google Scholar] [CrossRef]
  71. Rommel, S.; Belger, C.; Begouin, J.-M.; Plietker, B. Dual [Fe+Phosphine] Catalysis: Application in Catalytic Wittig Olefination. Chemcatchem 2015, 7, 1292–1301. [Google Scholar] [CrossRef]
  72. Werner, T.; Hoffmann, M.; Deshmukh, S. First Enantioselective Catalytic Wittig Reaction. Eur. J. Org. Chem. 2014, 6630–6633. [Google Scholar] [CrossRef]
  73. Wang, L.; Wang, Y.; Chen, M.; Ding, M.-W. Reversible P(III)/P(V) Redox: Catalytic Aza-Wittig Reaction for the Synthesis of 4(3H)-Quinazolinones and the Natural Product Vasicinone. Adv. Synth. Catal. 2014, 356, 1098–1104. [Google Scholar] [CrossRef]
  74. Werner, T.; Hoffmann, M.; Deshmukh, S. First Microwave-Assisted Catalytic Wittig Reaction. Eur. J. Org. Chem. 2014, 6873–6876. [Google Scholar] [CrossRef]
  75. Van Kalkeren, H.A.; te Grotenhuis, C.; Haasjes, F.S.; Hommersom, C.A.; Rutjes, F.P.J.T.; van Delft, F.L. Catalytic Staudinger/aza-Wittig sequence by in situ phosphane oxide reduction. Eur. J. Org. Chem. 2013, 7059–7066. [Google Scholar] [CrossRef]
  76. Beddoe, R.H.; Sneddon, H.F.; Denton, R.M. The catalytic Mitsunobu reaction: A critical analysis of the current state-of-the-art. Org. Biomol. Chem. 2018, 16, 7774–7781. [Google Scholar] [CrossRef]
  77. Hirose, D.; Gazvoda, M.; Košmrlj, J.; Taniguchi, T. The “Fully Catalytic System” in Mitsunobu Reaction Has Not Been Realized Yet. Org. Lett. 2016, 18, 4036–4039. [Google Scholar] [CrossRef]
  78. Buonomo, J.A.; Aldrich, C.C. Mitsunobu Reactions Catalytic in Phosphine and a Fully Catalytic System. Angew. Chem. Int. Ed. 2015, 54, 13041–13044. [Google Scholar] [CrossRef] [Green Version]
  79. Lenstra, D.C.; Wolf, J.J.; Mecinovic, J. Catalytic Staudinger Reduction at Room Temperature. J. Org. Chem. 2019, 84, 6536–6545. [Google Scholar] [CrossRef]
  80. Zhang, K.; Cai, L.; Yang, Z.; Houk, K.N.; Kwon, O. Bridged [2.2.1] bicyclic phosphine oxide facilitates catalytic γ-umpolung addition-Wittig olefination. Chem. Sci. 2018, 9, 1867–1872. [Google Scholar] [CrossRef] [Green Version]
  81. Lenstra, D.C.; Lenting, P.E.; Mecinovic, J. Sustainable organophosphorus-catalysed Staudinger reduction. Greem Chem. 2018, 20, 4418–4422. [Google Scholar] [CrossRef]
  82. Andrews, K.G.; Denton, R.M. A more critical role for silicon in the catalytic Staudinger amidation: Silanes as non-innocent reductants. Chem. Commun. 2017, 53, 7982–7985. [Google Scholar] [CrossRef] [PubMed]
  83. Saleh, N.; Blanchard, F.; Voituriez, A. Synthesis of Nitrogen-Containing Heterocycles and Cyclopentenone Derivatives via Phosphine-Catalyzed Michael Addition/Intramolecular Wittig Reaction. Adv. Synth. Catal. 2017, 359, 2304–2315. [Google Scholar] [CrossRef]
  84. Van Kalkeren, H.A.; Bruins, J.J.; Rutjes, F.P.J.T.; van Delft, F.L. Organophosphorus-catalyzed Staudinger reduction. Adv. Synth. Catal. 2012, 354, 1417–1421. [Google Scholar] [CrossRef]
  85. Longwitz, L.; Jopp, S.; Werner, T. Organocatalytic Chlorination of Alcohols by P(III)/P(V) Redox Cycling. J. Org. Chem. 2019, 84, 7863–7870. [Google Scholar] [CrossRef] [PubMed]
  86. Van Kalkeren, H.A.; Leenders, S.; Hommersom, C.R.A.; Rutjes, F.; van Delft, F.L. In situ phosphine oxide reduction: A catalytic Appel reaction. Chem. Eur. J. 2011, 17, 11290–11295. [Google Scholar] [CrossRef]
  87. Nykaza, T.V.; Ramirez, A.; Harrison, T.S.; Luzung, M.R.; Radosevich, A.T. Biphilic Organophosphorus-Catalyzed Intramolecular Csp2-H Amination: Evidence for a Nitrenoid in Catalytic Cadogan Cyclizations. J. Am. Chem. Soc. 2018, 140, 3103–3113. [Google Scholar] [CrossRef] [Green Version]
  88. White, P.B.; Rijpkema, S.J.; Bunschoten, R.P.; Mecinovic, J. Mechanistic Insight into the Catalytic Staudinger Ligation. Org. Lett. 2019, 21, 1011–1014. [Google Scholar]
  89. Nykaza, T.V.; Cooper, J.C.; Li, G.; Mahieu, N.; Ramirez, A.; Luzung, M.R.; Radosevich, A.T. Intermolecular Reductive C-N Cross Coupling of Nitroarenes and Boronic Acids by PIII/PV=O Catalysis. J. Am. Chem. Soc. 2018, 140, 15200–15205. [Google Scholar] [CrossRef] [Green Version]
  90. Hamstra, D.F.J.; Lenstra, D.C.; Koenders, T.J.; Rutjes, F.P.J.T.; Mecinovic, J. Poly(methylhydrosiloxane) as a green reducing agent in organophosphorus-catalyzed amide bond formation. Org. Biomol. Chem. 2017, 15, 6426–6432. [Google Scholar] [CrossRef] [Green Version]
  91. Fourmy, K.; Voituriez, A. Catalytic Cyclization Reactions of Huisgen Zwitterion with α-Ketoesters by in Situ Chemoselective Phosphine Oxide Reduction. Org. Lett. 2015, 17, 1537–1540. [Google Scholar] [CrossRef]
  92. Zhao, W.; Yan, P.K.; Radosevich, A.T. A Phosphetane Catalyzes Deoxygenative Condensation of α-Keto Esters and Carboxylic Acids via PIII/PV=O Redox Cycling. J. Am. Chem. Soc. 2015, 137, 616–619. [Google Scholar] [CrossRef] [PubMed]
  93. Kosal, A.D.; Wilson, E.E.; Ashfeld, B.L. Phosphine-Based Redox Catalysis in the Direct Traceless Staudinger Ligation of Carboxylic Acids and Azides. Angew. Chem. Int. Ed. 2012, 51, 12036–12040. [Google Scholar] [CrossRef] [PubMed]
  94. Rotstein, B.H.; Zaretsky, S.; Rai, V.; Yudin, A.K. Small Heterocycles in Multicomponent Reactions. Chem. Rev. 2014, 114, 8323–8359. [Google Scholar] [CrossRef] [PubMed]
  95. Estevez, V.; Villacampa, M.; Menendez, J.C. Recent advances in the synthesis of pyrroles by multicomponent reactions. Chem. Soc. Rev. 2014, 43, 4633–4657. [Google Scholar] [CrossRef]
  96. Cioc, R.C.; Ruijter, E.; Orru, R.V.A. Multicomponent reactions: Advanced tools for sustainable organic synthesis. Green Chem. 2014, 16, 2958–2975. [Google Scholar] [CrossRef]
  97. Wang, J.; Zhou, R.; He, Z.-R.; He, Z. Phosphane-Mediated Domino Synthesis of Tetrasubstituted Furans from Simple Terminal Activated Olefins. Eur. J. Org. Chem. 2012, 6033–6041. [Google Scholar] [CrossRef]
  98. Lawrence, N.J.; Crump, J.P.; McGown, A.T.; Hadfield, J.A. Reaction of Baylis–Hillman products with Swern and Dess–Martin oxidants. Tetrahedron Lett. 2001, 42, 3939–3941. [Google Scholar] [CrossRef]
Sample Availability: Samples of the compounds 3 are not available from the authors.
Molecules 24 04595 sch001 550
Scheme 1. Phosphine-mediated synthesis of tetra-substituted furans.
Scheme 1. Phosphine-mediated synthesis of tetra-substituted furans.
Molecules 24 04595 sch001
Molecules 24 04595 sch002 550
Scheme 2. Synthesis of tetra-substituted furans 3 from di-substituted alkene 1g and 1h.
Scheme 2. Synthesis of tetra-substituted furans 3 from di-substituted alkene 1g and 1h.
Molecules 24 04595 sch002
Molecules 24 04595 sch003 550
Scheme 3. Synthesis of tri-substituted furans 3 from methyl vinyl ketone 1i.
Scheme 3. Synthesis of tri-substituted furans 3 from methyl vinyl ketone 1i.
Molecules 24 04595 sch003
Molecules 24 04595 sch004 550
Scheme 4. Control experiments.
Scheme 4. Control experiments.
Molecules 24 04595 sch004
Molecules 24 04595 sch005 550
Scheme 5. Proposed mechanism.
Scheme 5. Proposed mechanism.
Molecules 24 04595 sch005
Table
Table 1. Survey of the model reaction conditions.a.
Table 1. Survey of the model reaction conditions.a.
Molecules 24 04595 i001
EntrySilane (mmol)SolventTemp (°C)3 (%) b
1Ph2SiH2 (0.6)THFrt11
2Ph2SiH2 (0.6)THF6012
3PhSiH3 (0.6)Toluenerttrace
4PhSiH3 (0.6)Toluene11074
5Ph2SiH2 (0.6)Toluene11042
6(MeO)3SiH (0.6)Toluene11033
7PMHS (0.034)Toluene11026
8PMHS (0.106)Toluene11030
9Ph3SiH (1.2)Toluene11018
10SiHCl3 (0.6)Toluenerttrace
11PhSiH3 (0.25)Toluene11065
12PhSiH3 (0.4)Toluene11084
13PhSiH3 (0.75)Toluene11049
14PhSiH3 (0.4)Toluene8056
15PhSiH3 (0.4)Dioxane11054
16PhSiH3 (0.4)Xylene11060
17PhSiH3 (0.4)DMF11011
18PhSiH3 (0.4)CH3CN80trace
19 cPhSiH3 (0.4)Toluene11048
a Typical conditions: a mixture of 1a (0.5 mmol), 2a (1.8 mmol), nBu3P (0.1 mmol), NEt3 (2.7 mmol) and silane in the specified solvent (2.0 mL) under N2 at indicated temperature for 24 h. b Isolated yield based on 1a. c The loading amount of nBu3P was 0.05 mmol.
Table
Table 2. Synthesis of tetra-substituted furans 3 from olefins 1 and acyl chlorides 2 or anhydride 2′.a
Table 2. Synthesis of tetra-substituted furans 3 from olefins 1 and acyl chlorides 2 or anhydride 2′.a
Molecules 24 04595 i002
EntryEWG in 1R in 2 or 2′3 (%) b
1CO2tBu (1a)3-ClC6H4 (2a)3aa, 84
2CO2tBu (1a)4-ClC6H4 (2b)3ab, 75
3CO2tBu (1a)2-ClC6H4 (2c)3ac, 33
4CO2tBu (1a)Ph(2d)3ad, 70
5CO2tBu (1a)4-MeC6H4 (2e)3ae, 90
6CO2tBu (1a)4-NO2C6H4 (2f)3af, 37
7CO2tBu (1a)2-thienyl (2g)3ag, 46
8CO2Me (1b)4-ClC6H4 (2b)3bb, 81
9CO2Me (1b)4-MeC6H4 (2e)3be, 84
10CO2Et (1c)4-ClC6H4 (2b)3cb, 71
11CO2Et (1c)4-MeC6H4 (2e)3ce, 84
12CO2nBu (1d)4-ClC6H4 (2b)3db, 85
13CO2nBu (1d)4-MeC6H4 (2e)3de, 83
14CO2Bn (1e)Ph (2d)3ed, 87
15CN (1f)4-ClC6H4 (2b)3fb, 38
16CN (1f)Ph (2d)3fd, 57
17CN (1f)4-MeC6H4 (2e)3fe, 44
18CO2tBu (1a)Me (2′a)3aa’, 27
a Optimized conditions: under a N2 atmosphere and at 110 °C, alkenes 1 (0.5 mmol) and acyl chlorides 2 or anhydride 2′ (1.8 mmol) were added into toluene (2.0 mL), followed by additions of nBu3P (0.1 mmol), NEt3 (2.7 mmol) and PhSiH3 (0.4 mmol), the resulting mixture was stirred for 24 h. b Isolated yield based on 1.

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Fan, X.; Chen, R.; Han, J.; He, Z. Convergent Synthesis of Polysubstituted Furans via Catalytic Phosphine Mediated Multicomponent Reactions. Molecules 2019, 24, 4595. https://doi.org/10.3390/molecules24244595

AMA Style

Fan X, Chen R, Han J, He Z. Convergent Synthesis of Polysubstituted Furans via Catalytic Phosphine Mediated Multicomponent Reactions. Molecules. 2019; 24(24):4595. https://doi.org/10.3390/molecules24244595

Chicago/Turabian Style

Fan, Xia, Rongshun Chen, Jie Han, and Zhengjie He. 2019. "Convergent Synthesis of Polysubstituted Furans via Catalytic Phosphine Mediated Multicomponent Reactions" Molecules 24, no. 24: 4595. https://doi.org/10.3390/molecules24244595

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