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Article

Bifunctionalized Allenes. Part XVI. Synthesis of 3-Phosphoryl-2,5-dihydrofurans by Coinage Metal-Catalyzed Cyclo-isomerization of Phosphorylated α-Hydroxyallenes

by
Valerij Ch. Christov
*,†,
Ismail E. Ismailov
† and
Ivaylo K. Ivanov
†
Department of Organic Chemistry & Technology, Faculty of Natural Sciences, Konstantin Preslavsky University of Shumen, 115, Universitetska str., BG-9712 Shumen, Bulgaria
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2015, 20(4), 7263-7275; https://doi.org/10.3390/molecules20047263
Submission received: 23 March 2015 / Revised: 15 April 2015 / Accepted: 17 April 2015 / Published: 21 April 2015
(This article belongs to the Section Organic Chemistry)
Browse Figures
Versions Notes

Abstract

:
Phosphorylated α-hydroxyallenes 1 and 2 were smoothly converted into the corresponding 2,5-dihydrofurans 3 and 4 in an 5-endo-trig cycloisomerization reaction by using 5 mol % of coinage metal salts as catalyst. Experimental conditions such as the type of the solvent, the reaction temperature, the mol % and the type of the catalyst were optimized. This mild and efficient cyclization method can be applied to dimethyl 1-hydroxyalkyl-alka-1,2-dienephosphonates 1 and 2-diphenylphosphinoyl-2,3-dien-1-ols 2a–c and 3-diphenylphosphinoyl-3,4-dien-2-ols 2d,e, furnishing 3-phosphorylated 2,5-dihydrofurans 3 and 4 in very good yields.

Graphical Abstract

1. Introduction

2,5-Dihydrofurans and their derivatives are structural subunits frequently found in a wide variety of natural products which find application as flavor and fragrance compounds and pharmaceuticals [1,2,3] and represent pivotal structural elements in a wide variety of different biologically active molecules. For instance, they can be found in mycotoxins such as verrucosidine [4] and the structurally related citreoviridine [5], as well as vitamin A metabolites [6], polyether antibiotics [7,8], spiroketals [9] and even amino acids [10]. 2,5-Dihydrofurans are also important intermediates in organic synthesis due to the presence of the C=C bond as well as the five-membered ring. Consequently, much attention has been paid to the development of efficient and diverse synthetic methods for construction of this five-membered ring system [11,12,13].
Transition metal-catalyzed cyclization of functionalized allenes bearing a nucleophilic center has attracted considearble attention in recent years [14]. Particularly, the cyclization reactions of allenols catalyzed by Ag(I) [15,16,17,18], Hg(II) [19,20], Pd(0) [21,22,23], Pd(II) [24,25], or Ru(III) [26,27] have become quite useful methodologies for the synthesis of five-, or six-membered oxygen-containing heterocycles. Krause’s group has reported a highly efficient and stereoselective synthesis of 2,5-dihydrofurans by Au(I)- and Au(III)-catalyzed [28,29,30,31,32,33] cycloisomerization of α-hydroxyallenes [34,35,36]. Moreover, the method is not restricted to the cycloisomerization of α-hydroxyallenes to 2,5-dihydrofurans [34,35], rather, it was recently extended by Krause’s group to the corresponding endo-cyclization of β-hydroxyallenes [37], α-/β-aminoallenes [37,38,39], and α-thioallenes [40] to the corresponding five- or six-membered O-, N-, or S-heterocycles. The method of choice, however, is the use of transition metal catalysts since this combines high reactivities and excellent yields with a tolerance to many functional groups.
On the other hand, the literature data on the reactions of phosphorylated allenes with electrophilic reagents reveal that the reactions proceed with cyclization of the allenic system bearing the phosphoryl group (O=P-C=C=C) to give heterocyclic compounds in most cases and the outcome depends on the structure of the starting allenic compound as well as the type of electrophile used [41,42,43,44]. Several diethylphosphono-substituted α-allenic alcohols [45] and glycols [46] were prepared by Brel [47,48] directly from alcohols by Horner-Mark rearrangement of unstable propargylic phosphites and used as starting materials for study of the cyclization in the presence of AgNO3 [46,47,49] and CuCl2 [48].
Our long-standing research program focuses on the development of efficient cyclization reactions of 1,1- [50,51] and 1,3-bifunctionalized allenes [52,53]. More specifically, our attention is drawn to phosphorylated hydroxyallenes as 1,1-bifunctionalized allenes that comprise a phosphoryl and a hydroxyalkyl group. The applications of these groups as temporary transformers of chemical reactivity of the allenic system in the synthesis of eventually heterocyclic compounds are of particular interest. These molecules can be considered a combination of an allenephosphonate or allenyl phosphine oxide and a hydroxyallene and they are supposed to have different reactivity profiles in cycloisomerization reactions. Our recent research has led to a significant result, whereby we have developed a convenient and efficient method for the regioselective synthesis of phosphorylated α-hydroxyallenes using an atom economical [2,3]-sigmatropic rearrangement [54]. In this paper, we present recent results of ongoing studies dedicated towards the optimization of the experimental conditions and the catalyst efficiency in the coinage metal salts-catalyzed cycloisomerization of α-hydroxyalkyl-allenephosphonates and phosphine oxides to 3-phosphorylated 2,5-dihydrofurans, which strongly improve the scope of this method.

2. Results and Discussion

In addition to our previously reported preparation [55] of 2,5-dihydro-1,2-oxaphospholes by electrophilic cyclization of the 1-hydroxyalkyl-allenephosphonates 1 and allenyl phosphine oxides 2 due to the participation of the phosphonate neighboring group in the 5-endo-trig cyclization, we carried out the cycloisomerization reaction of the abovementioned compounds 1 and 2 in the presence of coinage metal salts as catalysts. Our initial work began with the cycloisomerization reaction of the model α-hydroxyalkyl-allenephosponate 1a with AgNO3 in order to optimize the reaction conditions such as the influence of the solvent, the reaction temperature, the mol % and the type of the catalyst. The reaction occurred with formation of the dimethyl (5-ethyl-5-methyl-2,5-dihydrofuran-3-yl) phosphonate (3a, Scheme 1). The results are summarized in Table 1.
Molecules 20 07263 g001 550
Scheme 1. AgNO3-catalyzed cycloisomerization of the model dimethyl 1-hydroxymethyl-3-methylpenta-1,2-dienephosphonate (1a).
Scheme 1. AgNO3-catalyzed cycloisomerization of the model dimethyl 1-hydroxymethyl-3-methylpenta-1,2-dienephosphonate (1a).
Molecules 20 07263 g001
Table
Table 1. Optimization of the AgNO3-catalyzed cycloisomerization of the model dimethyl 1-hydroxymethyl-3-methylpenta-1,2-dienephosphonate (1a).
Table 1. Optimization of the AgNO3-catalyzed cycloisomerization of the model dimethyl 1-hydroxymethyl-3-methylpenta-1,2-dienephosphonate (1a).
EntrySolvent aReaction temperature (°C)AgNO3 (mol %)Yield b (%)
1ClCH2CH2Cl−201041
2ClCH2CH2Cl0555
3ClCH2CH2Clrt563
4ClCH2CH2Clreflux545
5CHCl3rt558
6EtOHrt546
7MeCNrt545
8THFrt540
9toluenert528
10acetonert551
11acetone/H2Ort575
12acetone/H2Ort1077
13CH2Cl2−20572
14CH2Cl2rt584 c
15CH2Cl2rt1082
a Reaction was carried out in the appropriate solvent (10 mL); b Yields determined by 1H and 31P-NMR analysis; c Isolated yield by chromatographic purification on silica gel.
At the very beginning, the reaction occurred in 1,2-dichloroethane at −20 °C with 10 mol % of catalyst (Table 1, entry 1). The yield was 41%. On the other hand, when we used 5 mol % of catalyst to carry out the reaction at 0 °C or room temperature in the same solvent the yield increased considerably (Table 1, entries 2 and 3). Lower yield was obtained at reflux in the same solvent (Table 1, entry 4). It is obvious that the optimal temperature for the cycloisomerization reaction of compound 1a is room temperature. The use of polar solvents such as chloroform, ethanol, acetonitrile and THF at room temperature with 5 mol % AgNO3 produces the product in relatively good yields (Table 1, entries 5–8). A lower yield occurred in toluene (Table 1, entry 9). When the solvent was a mixture of acetone and H2O [15] at room temperature the yield was 77% with 5 mol % of catalyst (Table 1, entries 11 and 12). The data confirm that the optimal conditions for cycloisomerization of model compound 1a (Table 1, entry 14) are methylene chloride, 5 mol % catalyst and room temperature. We found that reactions occurring at low or high reaction temperatures different from the optimum afford lower yields (Table 1, entries 2, 4 and 13). We also saw a lower yield when we used 10 mol % of catalyst at room temperature in dichloromethane (Table 1, entry 15). The type of catalyst and its influence on the yields of the cycloisomerization products of the α-hydroxyalkyl-allenephosphonates 1a–e was also of great interest to us. We thus conducted a series of experiments to optimize the reaction conditions of the model compound 1a (Scheme 2). We applied the following coinage metal salts as catalysts: AgNO3, AgClO4, AuCl, AuCl3, ZnCl2, NiCl2, PtCl2, SnCl2, AlCl3, PdCl2, Pd(PPh3)4, CuCl2, CuCl, CuBr, and CuI. The data reveal that both Au and Ag are excellent catalysts. Pd, Cu(II) and Pt are very good catalysts for our experiments. It becomes obvious that Zn, Ni, Sn and Al are relatively good catalysts. It is the Cu(I) catalysts that are bad. Table 2 presents the characteristics of all the above-mentioned catalysts in the cycloisomerization reaction of the model compound 1a.
Molecules 20 07263 g002 550
Scheme 2. Coinage metal-catalyzed cycloisomerization of the model dimethyl 1-hydroxymethyl-3-methylpenta-1,2-dienephosphonate 1a and the model 2-diphenylphosphinoyl-4-methylhexa-2,3-dien-1-ol 2a.
Scheme 2. Coinage metal-catalyzed cycloisomerization of the model dimethyl 1-hydroxymethyl-3-methylpenta-1,2-dienephosphonate 1a and the model 2-diphenylphosphinoyl-4-methylhexa-2,3-dien-1-ol 2a.
Molecules 20 07263 g002
The next step in our study was to explore the possibilities of the cycloisomerization reactions of the α-hydroxyalkyl-allenyl phosphine oxides 2a–e synthesized by us. At the very beginning, we used 2-diphenylphosphinoyl-4-methylhexa-2,3-dien-1-ol (2a) as a model compound. The optimal cycloisomerization conditions included dichloromethane as solvent, 5 mol % catalyst and room temperature. The reaction occurred via an 5-endo-trig cyclization to give 4-(diphenylphosphinoyl)-2-ethyl-2-methyl-2,5-dihydrofuran (4a, Scheme 2). We performed a series of experiments with the sole intention of determining the best catalysts bearing in mind two criteria—highest yield and shortest reaction time. The model compound 2a reacts with the catalysts shown in Table 2, in which the yields obtained and the reaction time of the preparation of isomer 4a are presented. The experimental data reveals that the best catalytic characteristics correspond to Au, Ag and Pd catalysts (Table 2). The Cu(II), Zn and Pt catalysts that show very good results. The Sn, Al and Ni are relatively good.
Table
Table 2. Optimization of the coinage metal-catalyzed cycloisomerization of the model compound 1a and the model dien-1-ol 2a.
Table 2. Optimization of the coinage metal-catalyzed cycloisomerization of the model compound 1a and the model dien-1-ol 2a.
EntryCatalystReaction time a (min)Yield b (%)
1a2a1a2a
1AuCl20309791
2AuCl330359489
3AgClO4305583 c85 c
4AgNO350658080
5PdCl21001157380
6Pd(PPh3)41051207477
7CuCl21151107774
8PtCl21351806678
9ZnCl21601355075
10NiCl22253955336
11SnCl23102553857
12AlCl33453403432
13CuCl5306352727
14CuBr5456902922
15CuI6007252423
a On the average; b Yields determined by 1H- and 31P-NMR analysis; c Isolated yield by chromatographic purification on silica gel.
The investigation on the cycloisomerization reaction of the synthesized series of α-hydroxyalkyl-allenephosphonates 1a–e was intended to be systematical. We applied the optimized reaction temperature, type of the solvent and molar ratio of the catalyst conditions in regard to the substrate. Having in mind that gold catalysts are expensive and sensitive to moisture, we decided to use AgClO4 as a main catalyst in cycloisomerization reaction in order to extend our study (Scheme 3). The results are explicit enough—a catalytic 5-endo-trig cycloisomerization occurs and the hydroxy group participates as an internal nucleophile to give the 2,5-dihydrofuran-3-yl phosphonates 3 in very good yields.
Molecules 20 07263 g003 550
Scheme 3. AgClO4-Catalyzed cycloisomerization of the phosphorylated α-hydroxyallenes 1 and 2.
Scheme 3. AgClO4-Catalyzed cycloisomerization of the phosphorylated α-hydroxyallenes 1 and 2.
Molecules 20 07263 g003
Our study was systematized also on the cycloisomerization of a series of α-hydroxyalkyl-allenyl phosphine oxides 2a–e in methylene chloride at room temperature (Scheme 3). Moreover, it was the AgClO4 catalyst, which is easily accessible and relatively good, that was used in our research. The results are undisputable—the 3-diphenylphosphinoyl-2,5-dihydrofurans 4 are produced as a result of the participation of the neighboring hydroxy group as an internal nucleophile in the cyclization process. Table 3 shows the reaction times and yields of the cycloisomerization reaction of the α-hydroxyalkyl-allenephosphonates 1a–e and allenyl phosphine oxides 2a–e.
Table
Table 3. AgClO4-Catalyzed cycloisomerization of the phosphorylated α-hydroxyallenes 1 and 2.
Table 3. AgClO4-Catalyzed cycloisomerization of the phosphorylated α-hydroxyallenes 1 and 2.
EntryAlleneYRR1R2R3Reaction time a (min)Product, Yield b (%)
11aMeOHHMeEt303a, 83
21bMeOHHMeBu353b, 75
31cMeOHH-(CH2)5-413c, 73
41dMeOHMeMeEt333d, 77
51eMeOMeMeMeBu403e, 74
62aPhHHMeEt554a, 85
72bPhHHMeBu584b, 85
82cPhHH-(CH2)5-754c, 82
92dPhHMeMeEt574d, 84
102ePhMeMeMeBu644e, 82
a On the average; b Isolated yield by chromatographic purification on silica gel.

3. Experimental Section

3.1. General Information

All new synthesized compounds were purified by column chromatography and characterized on the basis of NMR, IR, and microanalytical data. NMR spectra were recorded on DRX Bruker Avance-250 (Bruker BioSpinGmbH, Karlsruhe, Germany) (1H at 250.1 MHz, 13C at 62.9 MHz, 31P at 101.2 MHz) and Bruker Avance II+600 (Bruker BioSpinGmbH) (1H at 600.1 MHz, 13C at 150.9 MHz, 31P at 242.9 MHz) spectrometers for solutions in CDCl3. All 1H- and 13C-NMR experiments were measured referring to the signal of internal TMS and 31P-NMR experiments were measured referring to the signal of external 85% H3PO4. J values are given in Hertz. IR spectra were recorded with an Afinity-1 FT-IR spectrophotometer (Shimadzu, Tokyo, Japan). Elemental analyses were carried out by the Microanalytical Service Laboratory of Faculty of Chemistry and Pharmacy, University of Sofia, Sofia, Bulgaria, using Vario EL3 CHNS(O) (Elementar Analysensysteme, Hanau, Germany). Column chromatography was performed on Kieselgel F25460 (70–230 mesh ASTM, 0.063–0.200 nm, Merck, Darmstadt, Germany). Reactions were carried out in oven dried glassware under an argon atmosphere and exclusion of moisture. All compounds were checked for purity on Kieselgel F25460 TLC plates (Merck).

3.2. Starting Materials

The starting phosphorylated α-hydroxyallenes 1 and 2 were prepared according to the established procedure [54]. CH2Cl2 was distilled over CaH2 and other organic solvents used in this study were dried over appropriate drying agents by standard methods and distilled prior to use. All other chemicals used in this study were commercially available and were used without additional purification unless otherwise noted.

3.3. General Procedure for the Coinage Metal-catalyzed Cycloisomerization of the 1-Hydroxyalkyl-1,2-dienephosphonates 1

Metal salt catalyst (0.15 mmol) was added to a solution of the 1-hydroxyalkyl-1,2-dienephosphonate 1 (3.0 mmol) in dry dichloromethane (10 mL). The mixture was stirred at room temperature and in the dark for the minutes indicated in the Table 3. Saturated sodium chloride solution was added to precipitate the silver ions. The product was extracted by chloroform. The organic layer was dried over anhydrous sodium sulfate. After evaporation of the solvent, the residue was chromatographed on a column (silica gel, Kieselgel Merck 60 F254) with a mixture of ethyl acetate and hexane (6:1) as an eluent to give the pure products 3 as oils, which had the following properties:
Dimethyl (5-ethyl-5-methyl-2,5-dihydrofuran-3-yl)phosphonate (3a). This compound was obtained as a yellow oil, yield 83%. Rf 0.44; IR (neat, νmax, cm−1): 1128 (C-O-C), 1254 (P=O), 1627 (C=C). 1H-NMR (250.1 MHz): δH 0.89 (t, J = 7.4 Hz, 3H, Me-CH2), 1.32 (s, 3H, Me-C), 1.60-1.72 (m, 2H, Me-CH2), 3.76 (d, J = 12.2 Hz, 3H, MeO), 4.73–4.77 (m, 2H, CH2O), 6.53–6.57 (m, 1H, =CH). 13C-NMR (62.9 MHz) δC 8.6, 25.2 (J = 2.0 Hz), 33.0 (J = 4.5 Hz), 52.5 (J = 5.6 Hz), 74.9 (J = 20.5 Hz), 92.3 (J = 19.1 Hz), 127.5 (J = 195.9 Hz), 149.6 (J = 10.1 Hz). 31P-NMR (101.2 MHz): δP 15.9. Anal. Calcd for C9H17O4P requires: C 49.09, H 7.78. Found: C 49.12, H 7.74.
Dimethyl (5-butyl-5-methyl-2,5-dihydrofuran-3-yl)phosphonate (3b). This compound was obtained as a yellow oil, yield 75%. Rf 0.40; IR (neat, νmax, cm−1): 1120 (C-O-C), 1258 (P=O), 1626 (C=C). 1H-NMR (600.1 MHz): δH 0.88 (t, J = 7.2 Hz, 3H, Me-CH2), 1.19–1.26, 1.28–1.37, 1.56–1.67 (overlapping multiplets, 6H, (CH2)3-Me), 1.31 (s, 3H, Me-C), 3.75 (d, J = 12.0 Hz, 3H, MeO), 4.71–4.78 (m, 2H, CH2O), 6.54–6.57 (m, 1H, =CH). 13C-NMR (150.9 MHz) δC14.1, 23.1, 25.5 (J = 2.1 Hz), 26.7, 40.0 (J = 4.5 Hz), 52.6 (J = 5.7 Hz), 74.8 (J = 20.6 Hz), 92.1 (J = 19.2 Hz), 127.6 (J = 196.1 Hz), 149.8 (J = 10.1 Hz). 31P-NMR (242.9 MHz): δP 16.0. Anal. Calcd for C11H21O4P requires: C 53.22, H 8.53. Found: C 53.18, H 8.55.
Dimethyl (1-oxaspiro[4.5]dec-3-en-3-yl)phosphonate (3c). This compound was obtained as an orange oil, yield 73%. Rf 0.60; IR (neat, νmax, cm−1): 1126 (C-O-C), 1257 (P=O), 1625 (C=C). 1H-NMR (250.1 MHz): δH 1.22–1.45, 1.4–1.72, 1.8–2.02 (overlapping multiplets, 10H, (CH2)5), 3.77 (d, J = 12.5 Hz, 3H, MeO), 4.73–4.75 (m, 2H, CH2O), 6.72–6.75 (m, 1H, =CH). 13C-NMR (62.9 MHz) δC23.4, 25.8, 35.4 (J = 4.5 Hz), 52.6 (J = 5.6 Hz), 73.8 (J = 20.8 Hz), 91.4 (J = 19.1 Hz), 126.4.5 (J = 196.2 Hz), 149.9 (J = 9.8 Hz). 31P-NMR (101.2 MHz): δP 17.1. Anal. Calcd for C11H19O4P requires: C 53.65, H 7.78. Found: C 53.62, H 7.70.
Dimethyl (2-methyl-1-oxaspiro[4.5]dec-3-en-3-yl)phosphonate (3d). This compound was obtained as an orange oil, yield 77%. Rf 0.59; IR (neat, νmax, cm−1): 1119 (C-O-C), 1251 (P=O), 1624 (C=C). 1H-NMR (600.1 MHz): δH 1.21–1.31, 1.34–1.52, 1.68–1.89 (overlapping multiplets, 10H, (CH2)5), 1.38 (d, J = 6.4 Hz, 3H, Me-CH), 3.75 (d, J = 11.2 Hz, 3H, MeO), 5.01–5.05 (m, 1H, Me-CH), 6.75–6.79 (m, 1H, =CH). 13C-NMR (150.9 MHz) δC 20.5 (J = 9.9 Hz), 20.6 (J = 4.5 Hz), 23.1, 26.8, 34.9 (J = 4.6 Hz), 52.5 (J = 5.7 Hz), 74.2 (J = 20.5 Hz), 91.9 (J = 19.3 Hz), 127.0 (J = 196.0 Hz), 149.7 (J = 10.0 Hz). 31P-NMR (242.9 MHz): δP 17.0. Anal. Calcd for C12H21O4P requires: C 55.38, H 8.13. Found: C 55.44, H 8.09.
Dimethyl (5-butyl-2,2,5-trimethyl-2,5-dihydrofuran-3-yl)phosphonate (3e). This compound was obtained as a yellow oil, yield 74%. Rf 0.56; IR (neat, νmax, cm−1): 1117 (C-O-C), 1257 (P=O), 1622 (C=C). 1H-NMR (600.1 MHz): δH 0.88 (t, J = 7.1 Hz, 3H, Me-CH2), 1.19–1.39, 1.41–1.53, 1.56–1.65 (overlapping multiplets, 6H, Me-(CH2)3), 1.33 (s, 3H, Me-C), 1.44, 1.46 (ss, 6H, Me2C), 3.76 (d, J = 11.2 Hz, 3H, MeO), 6.57–6.59 (m, 1H, =CH). 13C-NMR (150.9 MHz) δC14.2, 23.5, 25.7 (J = 2.0 Hz), 27.1, 28.5, 28.7, 41.1 (J = 4.6 Hz), 52.5 (J = 5.8 Hz), 74.9 (J = 20.4 Hz), 89.7 (J = 19.2 Hz), 127.1 (J = 196.1 Hz), 150.3 (J = 10.1 Hz). 31P-NMR (242.9 MHz): δP 17.2. Anal. Calcd for C13H25O4P requires: C 56.51, H 9.12. Found: C 56.57, H 9.17.

3.4. General Procedure for the Coinage Metal-catalyzed Cycloisomerization of the 2-Diphenylphosphinoyl-2,3-dien-1-ols 2a-c and the 3-Diphenylphosphinoyl-3,4-dien-2-ols 2d,e

Metal salt catalyst (0.15 mmol) was added to a solution of the 2-diphenylphosphinoyl-2,3-dien-1-ols 2a–c or the 3-diphenylphosphinoyl-3,4-dien-2-ols 2d,e (3.0 mmol) in dry dichloromethane (10 mL). The mixture was stirred at room temperature and in the dark for the minutes indicated in the Table 3. Saturated sodium chloride solution was added to precipitate the metal ions. The product was extracted by dichloromethane. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed using a rotatory evaporator and the residue was purified by column chromatography (silica gel, Kieselgel Merck 60 F254) with a mixture of ethyl acetate and hexane (5:1). The pure products 4 had the following properties:
Diphenyl (5-ethyl-5-methyl-2,5-dihydrofuran-3-yl) phosphine oxide (4a). This compound was obtained as a colourless oil, yield 85%. Rf 0.58; IR (neat, νmax, cm−1): 1121 (C-O-C), 1174 (P=O), 1436, 1483 (Ph), 1620 (C=C). 1H-NMR (600.1 MHz): δH 0.91 (t, J = 7.5 Hz, 3H, Me-CH2), 1.33 (s, 3H, Me-C), 1.61–1.73 (m, 2H, Me-CH2), 4.78–4.86 (m, 2H, CH2O), 6.27–6.31 (m, 1H, =CH), 7.39–7.78 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δC 8.98, 25.3 (J = 2.1 Hz), 33.0 (J = 4.4 Hz), 75.5 (J = 17.1 Hz), 92.7 (J = 14.9 Hz), 133.5 (J = 104.0 Hz), 128.1–132.9, 149.6 (J = 7.3 Hz). 31P-NMR (242.9 MHz): δP 22.2. Anal. Calcd for C19H21O2P requires: C 73.06, H 6.78. Found: C 73.02, H 6.83.
Diphenyl (5-butyl-5-methyl-2,5-dihydrofuran-3-yl) phosphine oxide (4b). This compound was obtained as a colourless oil, yield 85%. Rf 0.52; IR (neat, νmax, cm−1): 1120 (C-O-C), 1178 (P=O), 1437, 1492 (Ph), 1618 (C=C). 1H-NMR (600.1 MHz): δH 0.89 (t, J = 7.1 Hz, 3H, Me-CH2), 1.22–1.41, 1.59–1.69 (overlapping multiplets, 6H, (CH2)3-Me), 1.34 (s, 3H, Me-C), 4.77–4.84 (m, 2H, CH2O), 6.28–6.31 (m, 1H, =CH), 7.47–7.72 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δC 14.1, 23.8, 25.0, 25.8 (J = 2.0 Hz), 40.2 (J = 4.6 Hz), 75.3 (J = 17.0 Hz), 92.4 (J = 15.0 Hz), 128.7–132.4, 133.7 (J = 103.6 Hz), 149.7 (J = 7.3 Hz). 31P-NMR (242.9 MHz): δP 21.0. Anal. Calcd for C21H25O2P requires: C 74.10, H 7.40. Found: C 74.05, H 7.46.
Diphenyl (1-oxaspiro[4.5]dec-3-en-3-yl) phosphine oxide (4c). This compound was obtained as a yellow oil, yield 82%. Rf 0.55; IR (neat, νmax, cm−1): 1120 (C-O-C), 1169 (P=O), 1439, 1491 (Ph), 1622 (C=C). 1H-NMR (600.1 MHz): δH 1.32–1.38, 1.47–1.55, 1.64–1.74 (overlapping multiplets, 10H, (CH2)5), 4.77–4.79 (m, 2H, CH2O), 6.45–6.50 (m, 1H, =CH), 7.48–7.70 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δC 23.0, 25.3, 35.8 (J = 4.4 Hz), 74.3 (J = 17.0 Hz), 91.6 (J = 14.8 Hz), 128.3–134.2, 133.0 (J = 103.7 Hz), 149.8 (J = 7.3 Hz). 31P-NMR (242.9 MHz): δP 21.2. Anal. Calcd for C21H23O2P requires: C 74.54, H 6.85. Found: C 74.50, H 6.79.
Diphenyl (2-methyl-1-oxaspiro[4.5]dec-3-en-3-yl) phosphine oxide (4d). This compound was obtained as a yellow oil, yield 84%. Rf 0.47; IR (neat, νmax, cm−1): 1119 (C-O-C), 1173 (P=O), 1439, 1485 (Ph), 1621 (C=C). 1H-NMR (600.1 MHz): δH 1.18 (d, J = 6.4 Hz, 3H, Me-CH), 1.32–1.38, 1.42–1.54, 1.55–1.64 (overlapping multiplets, 10H, (CH2)5), 5.06–5.09 (m, 1H, Me-CH), 6.97–6.96 (m, 1H, =CH), 7.30–7.69 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δC 20.2 (J = 9.8 Hz), 20.5 (J = 4.6 Hz), 22.2, 26.5, 34.7 (J = 4.7 Hz), 82.4 (J = 15.8 Hz), 89.8 (J = 15.3 Hz), 128.4–135.0, 136.8 (J = 102.4 Hz), 149.7 (J = 7.8 Hz). 31P-NMR (242.9 MHz): δP 22.2. Anal. Calcd for C22H25O2P requires: C 74.98, H 7.15. Found: C 75.05, H 7.11.
Diphenyl (5-butyl-2,2,5-trimethyl-2,5-dihydrofuran-3-yl) phosphine oxide (4e). This compound was obtained as a colourless oil, yield 82%. Rf 0.46; IR (neat, νmax, cm−1): 1115 (C-O-C), 1163 (P=O), 1438, 1483 (Ph), 1624 (C=C). 1H NMR (600.1 MHz): δH 0.87 (t, J = 7.2 Hz, 3H, Me-CH2), 1.27–1.36, 1.49–1.54 (overlapping multiplets, 6H, (CH2)3-Me), 1.32 (s, 3H, Me-C), 1.45, 1.48 (ss, 6H, Me2C), 6.90–6.96 (m, 1H, =CH), 7.46–7.79 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δC 14.1, 23.8, 25.0, 26.3 (J = 2.1 Hz), 27.5, 27.7, 40.3 (J = 4.7 Hz), 83.5 (J = 16.0 Hz), 91.0 (J = 14.5 Hz), 128.6–134.7, 133.5 (J = 103.4 Hz), 144.9 (J = 7.6 Hz). 31P-NMR (242.9 MHz): δP 22.1. Anal. Calcd for C23H29O2P requires: C 74.98, H 7.93. Found: C 74.93, H 8.01.

4. Conclusions

In conclusion, we have developed a coinage metal-catalyzed cycloisomerization of phosphorylated α-hydroxyallenes, which provides an efficient route to 3-phosphorylated 2,5-dihydrofurans. Due to the ready availability of the starting materials and the catalyst, the convenient operation and mild conditions (room temperature, short reaction time), the very good yields and the usefulness of the resulting 2,5-dihydrofuran products, the reaction shows potential and will be useful in organic synthesis as well in the application of the method in target-oriented synthesis. Further investigation on the chemistry of other phosphorylated allenols for the synthesis of different heterocyclic systems is being intensively carried out in our laboratory. Moreover, results of an initial investigation of the biological activity of the compounds prepared were encouraging, and the antibacterial and antifungal activities of selected compounds are now under investigation in our University.

Acknowledgements

Financial support of our work by the Research Fund of the Konstantin Preslavsky University of Shumen (Projects Nos. RD-08-208/2014 and RD-08-248/2015), National Research Fund of Bulgaria (Project No. DRNF-02-13/2009) and Human Resources Development Operational Programme of the European Union (BG051PO001-3.3.06-0003/2012) is gratefully acknowledged.

Author Contributions

V.C.C. proposed the subject, designed the study and offered necessary guidance to I.E.I. and I.K.I. V.C.C. and I.K.I. conceived and designed the experiments. I.E.I. and I.K.I. performed the experiments under the supervision of the lead author V.C.C. who analyzed the spectral data and wrote the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

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  • Sample Availability: Samples of the compounds 1, 2, 3 and 4 are available from the authors.

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Christov, V.C.; Ismailov, I.E.; Ivanov, I.K. Bifunctionalized Allenes. Part XVI. Synthesis of 3-Phosphoryl-2,5-dihydrofurans by Coinage Metal-Catalyzed Cyclo-isomerization of Phosphorylated α-Hydroxyallenes. Molecules 2015, 20, 7263-7275. https://doi.org/10.3390/molecules20047263

AMA Style

Christov VC, Ismailov IE, Ivanov IK. Bifunctionalized Allenes. Part XVI. Synthesis of 3-Phosphoryl-2,5-dihydrofurans by Coinage Metal-Catalyzed Cyclo-isomerization of Phosphorylated α-Hydroxyallenes. Molecules. 2015; 20(4):7263-7275. https://doi.org/10.3390/molecules20047263

Chicago/Turabian Style

Christov, Valerij Ch., Ismail E. Ismailov, and Ivaylo K. Ivanov. 2015. "Bifunctionalized Allenes. Part XVI. Synthesis of 3-Phosphoryl-2,5-dihydrofurans by Coinage Metal-Catalyzed Cyclo-isomerization of Phosphorylated α-Hydroxyallenes" Molecules 20, no. 4: 7263-7275. https://doi.org/10.3390/molecules20047263

APA Style

Christov, V. C., Ismailov, I. E., & Ivanov, I. K. (2015). Bifunctionalized Allenes. Part XVI. Synthesis of 3-Phosphoryl-2,5-dihydrofurans by Coinage Metal-Catalyzed Cyclo-isomerization of Phosphorylated α-Hydroxyallenes. Molecules, 20(4), 7263-7275. https://doi.org/10.3390/molecules20047263

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