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Facile synthesis of α-alkoxymethyltriphenylphosphonium iodides: new application of PPh3/I2

  • Humaira Yasmeen Gondal
  • Zain Maqsood Cheema
  • Javid Hussain Zaidi
  • Sammer Yousuf
  • M. Iqbal Choudhary
Open Access
Research Article
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  1. Organic and Medicinal Chemistry

Abstract

An efficient one pot method for the synthesis of α-alkoxymethylphosphonium iodides is developed by using PPh3/I2 combination at room temperature. Reaction conditions are found general to synthesize wide range of structurally variant alkoxymethylphosphonium iodides in high yield (70–91%). These new functionalized phosphonium salts are further used in stereoselective synthesis of vinyl ethers as well as in carbon homologation of aldehydes.

Keywords

Bis-alkoxymethane PPh3/I2 Quaternary phosphonium salts O,P-acetals Carbon homologation Alkoxymethylphosphonium iodides 

Introduction

Functionalized phosphonium salts are gaining much attention for their diverse applications in organic synthesis [1, 2, 3, 4, 5]. α-Alkoxymethyl phosphonium salts are largely used for carbon homologation to carbonyl compounds [6, 7, 8, 9, 10] and also as significant synthetic intermediates [11, 12, 13, 14, 15, 16, 17]. Recently, unique reactivity of this class has been explored in nucleophilic substitution [18, 19, 20] and in novel phenyl transfer reactions [21, 22]. Methoxymethyltriphenylphosphonium chloride is commercially available salt from this class, but problem associated with its preparation involve toxic intermediate, higher temperature and long reaction time [9, 11, 23]. In perspective of alternative derivatives; α-methoxymethyl triphenylphosphonium iodide was reported by reaction of bis-methoxymethane (1a) with TMSI, followed by phosphination of methoxymethyl iodide in benzene (Scheme 1a) [24]. This only available method for iodide analogue also involves sensitive and toxic; reagent, solvent as well as intermediate along with difficult purification of product. In past few years, PPh3/I2 combination has successfully facilitated many functional groups inter-conversions [25, 26, 27, 28, 29, 30, 31, 32]. Therefore, we decided to explore reactivity of PPh3/I2 with bis-alkoxymethanes (1) and herein efficient synthesis of a broad range of structurally diverse α-alkoxymethyl triphenylphosphonium iodides (2) is being reported (Scheme 1b). To best of our knowledge, this is the first report on general one pot synthesis of O,P-acetals, directly from dioxacetals on employing PPh3/I2 combination (Scheme 1b).
Scheme 1

Synthesis of α-alkoxymethyl triphenylphosphonium iodides 2

Results and discussion

Current study was initiated from the model reaction of bis-butoxy methane (1a) with PPh3/I2 combination under different conditions (Table 1). Our preliminary attempt was encouraging, where 27% desired conversion (2a) was observed on refluxing equal molar amounts of acetal (1a) and PPh3/I2 in toluene for an hour (Table 1, entry 1). To improve the yield, reaction time was increased up to 3 h but only 33% required conversion was observed (Table 1, entry 2). Low yield might be associated with the sublimation of iodine at high temperature therefore, it was considered to decrease the reaction temperature. To our delight, yield was increased to 55% when the same experiment was performed at room temperature (Table 1, entry 3). Increasing the amount of PPh3 to 2 equivalent and reaction time up to 5 h further improved the yield (80%) (Table 1, entry 4). However, further attempts with increase in reaction time and replacing toluene with acetonitrile or solvent free conditions, were not effectual (Table 1, entry 5–8).
Table 1

Conditions optimization for conversion of dioxacetal to O,P-acetal (2a) Open image in new window

Entry

Solvent

Time (h)

Temperature (°C)

Yield (%)

1

Toluene

01

80

27

2

Toluene

03

80

33

3

Toluene

03

Room temp

55

4 a

Toluene

05

Room temp

80

5

Toluene

06

Room temp

69

6

02

Room temp

35

7

Acetonitrile

04

40

17

8

Acetonitrile

02

80

Traces

aBest optimized conditions

To explore the substrate scope of this reaction, optimized conditions were employed to structurally different bis-alkoxy methanes (1aj, see Additional file 1) [33]. The method was found equally efficient to obtain broad range of alkoxymethylphosphonium iodides (2aj, Table 2) based on primary, secondary, tertiary and benzylic alkoxy groups. Acetals having simple methoxy, ethoxy, benzoxy and phenylethoxy groups provided desired O,P-acetals 2be in 75–87%. Similarly, when acetal of (S)-2-butanol was reacted with PPh3/I2, corresponding salt 2f was obtained in 90% yield with retention in configuration, which was ultimately confirmed by X-ray diffraction analysis (Fig. 1).
Table 2

PPh3/I2 mediated synthesis of alkoxymethylphosphonium iodides (2aj)

Fig. 1

ORTEP diagram of (S)-2-sec-butoxymethyltriphenylphosphonium iodide 2f

Optimized reaction conditions were further extended to cyclic chiral alkoxy groups including fenchyl, menthyl and borneyl, where respective chiral phosphonium salts 2gi were obtained in good yields (Table 2).

Here, (+)-menthoxymethyltriphenylphosphonium iodide 2h is worth mentioning as its chloride analogue was prepared by tedious methodology with long reaction time [12]. Interestingly, the reaction was also successful with acetal of t-butanol where corresponding salt 2j was produced in 77% yield (Table 2).

In terms of mechanism, we envision that initially I2 and PPh3 generate phosphonium intermediate (i), which reacts with bis-alkoxymethane 1 to provide oxonium intermediate (ii) (Scheme 2). Another equivalent of PPh3 attack on oxonium intermediate (ii) to transform it into the target O,P-acetal 2 (Scheme 2).
Scheme 2

Plausible mechanism for the preparation of alkoxymethylphosphonium iodides 2

After having a range of alkoxymethylphosphonium iodides in hand, we further explored their applications in organic synthesis. Vinyl ethers also known as enol ethers are considered important synthetic targets for the organic chemists. They itself are part of many natural products and also involve as intermediate in their total synthesis [34, 35, 36]. They act as key intermediates in many important organic reactions like Diels–Alder reaction [37], Coupling reaction [38, 39, 40, 41, 42, 43], Olefin metathesis [44], Claisen rearrangement [45, 46] and Nazarov cyclization [47, 48]. They are also used in materials sciences due to their polymerization ability through cationic mechanism [49]. Despite extensive applications of enol ethers, still there is lack of general and direct method for their synthesis. Metal-catalyzed couplings are the most common available method [50, 51, 52, 53, 54], along with some other indirect methodologies [55, 56, 57, 58, 59, 60, 61, 62]. Direct synthesis of enol ethers by a Wittig reaction with alkoxymethylphosphonium salt is though an evident concept but no systematic study is found in literature. Most often commercially available methoxymethylphosphonium chloride is used [63, 64], whereas effect of other alkoxy groups as well as counter anions is still need to explore. For this purpose, at first ethoxymethyltriphenylphosphanium iodide 2c was reacted with benzaldehyde and its derivatives in the presence of n-BuLi, which afforded corresponding vinyl ethers 3ad (Table 3) in good yield (67–71%) and selectivity (69–73% trans).
Table 3

α-Alkoxymethylphosphonium iodides 2 in synthesis of vinyl ethers 3 Open image in new window

aDetermined by 1H-NMR

Providentially, trans isomer 3e′ was obtained almost exclusively (99% selectivity) with (+)-menthoxymethyltriphenylphosphonium iodide 2h. Earlier, Fuwa and Sasaki obtained same isomer 3e′ in 9% yield along with 36% cis isomer 3e through Pd coupling [40].

Further, cost effective n-butoxymethylphosphonium iodide 2a was employed for carbon homologation, where both aliphatic and aromatic aldehydes were successfully converted to higher analogous 4 in good yield (Table 4). Results show that these directly prepared and environmentally benign salts are good alternative to their chloride analogues.
Table 4

α-Butoxymethylphosphonium iodide 2a in carbon homologation of aldehydes Open image in new window

Entry

Substrate

Product (4)

Yield (%)

1.

PhCHO

PhCH2CHO

72

2.

EtCHO

n-PrCHO

71

3.

n-PrCHO

n-BuCHO

73

4.

n-BuCHO

n-PentCHO

70

To evaluate catalytic potential of chiral phosphonium salts in asymmetric reduction of acetophenone, initially 10 mol% of 2g with NaBH4 provided (R)-1-phenylethanol with 92% yield and 4% ee (Scheme 3).
Scheme 3

α-Alkoxymethylphosphonium iodide 2g in asymmetric reduction

Detailed study and further investigation on the application of these structurally unique α-alkoxymethylphosphonium salts in stereoselective synthesis of enol ethers carrying chiral auxillaries as well as in other related fields are currently underway in our laboratory.

Conclusion

In conclusion, a facile general method for the synthesis of α-alkoxymethyl triphenylphosphonium iodides is developed under very mild conditions. This protocol demonstrates PPh3/I2 mediated green route to functionalized phosphonium salts. Major advantage of this methodology is to avoid toxic reagent and intermediate. These easily prepared salts were successfully employed for stereoselective synthesis of enol ethers as well as for carbon homologation in aldehydes. The new methodology will be useful for organic synthetic chemists as well as others working in associated fields.

Experimental

All experiments were carried out under inert atmosphere using standard Schlenk technique with oven dried glassware and magnetic stirring. All solvents were freshly dried and distilled before use. All chemicals were purchased from Sigma Aldrich, Alfa Aesar and Merck. IR spectra were measured on a Perkin–Elmer Paragon 1000 (thin film) or on a Perkin–Elmer BXII spectrometer (neat). Bruker Avance NMR spectrometer of 300, 400 and 500 MHz were used for NMR spectral studies. Optical rotation was measured on Polarimeter P-2000. Crystal structure was confirmed by single crystal X-ray diffractometer Bruker Enrauf–Nonius Apex smart and Siemens P4. Mass spectra were measured on GC–MS 5977A, MAT312-EI, JEOL-600H-2, and JEOL MS-600H-1. Reactions were monitored by TLC plates from Merck (silica gel 60 F254, aluminum oxide 60 F254). TLCs were visualized by UV fluorescence and phosphomolybdic acid spraying reagent.

General procedure for synthesis of α-alkoxymethyltriphenylphosphonium iodides (2aj)

In a seal tube triphenylphosphine (20 mmol) and iodine (1.1 equiv) were taken in toluene (4 mL) and mixture was allowed to stir for 5 min. Solution of bis-alkoxymethane (1, 10 mmol in 1 mL toluene) was added to the reaction mixture and allowed to stir for 5 h at room temperature (28 °C). After completion of reaction, solvent was removed under reduced pressure and residue was washed with hexane to obtain required salt.

Butoxymethyltriphenylphosphonium iodide (2a)

Lemon yellow thick oil, yield = 80%, IR: υ (cm−1) = 689, 730, 1115, 1302, 1412, 2835. 1H-NMR (300 MHz, MeOD): δ ppm. 7.93–7.91 (3H, m, CH aromatic), 7.90–7.89 (3H, m, CH aromatic), 7.88–7.79 (2H, m, CH aromatic), 7.78–7.76 (3H, m, CH aromatic), 7.76–7.75 (3H, m, CH aromatic), 7.74–7.72 (1H, m, CH aromatic), 5.40 (2H, d, J = 4.8, CH2), 3.71 (2H, t, J = 6.4, CH2), 1.56–1.51 (2H, m, CH2), 1.28–1.22 (2H, m, CH2), 0.84 (3H, t, J = 7.6, CH3). 13C-NMR (75 MHz, MeOD): δ ppm. 136.62, 136.60 (2 carbons), 135.25, 135.15, 133.74 (3 carbons), 133.08, 132.97 (3 carbons), 131.55, 131.42, 130.01, 129.89 (2 carbons), 118.60, 117.74, 75.88, 35.76, 20.07, 13.99. 31P (202 MHz, CDCl3): δ ppm 18.83. EIMS = 349 (M+-I), 277.2 (48.4%), 262.2 (100%), 183.1 (59.6%), 108.0 (57.2%), 56 (36.3%).

Methoxymethyltriphenylphosphonium iodide (2b) [25]

Lemon yellow thick oil, yield = 73%, IR: υ (cm−1) = 691, 724, 1112, 1437, 2877, 2958. 1H-NMR (300 MHz, CDCl3): δ ppm 7.69–7.66 (3H, m, C–H aromatic), 7.65–7.61 (5H, m, C–H aromatic), 7.59–7.57 (2H, m, C–H aromatic), 7.56–7.51 (5H, m, C–H aromatic), 5.56 (2H, d, J = 3.9, CH2), 3.51 (3H, s, CH3). 13C-NMR (75 MHz, CDCl3): δ ppm. 135.77, 135.39, 135.35, 134.34 (3 carbons), 133.97, 133.84, 133.62, 133.49 (2 carbons), 130.78, 130.47, 130.30, 130.05, 129.89 (3 carbons), 116.85, 66.19. 31P (202 MHz, CDCl3): δ ppm 17.53. EIMS = 307 (M+-I), 277.2 (100%), 262.2 (67.6%), 183.1 (54.9%), 108.0 (10.9%), 77.0 (9.8%), 50.9 (5.6%).

Ethoxymethyltriphenylphosphanium iodide (2c)

Colorless oil: yield = 82%, IR: υ (cm−1) = 2846, 2794, 1946, 1586, 1484, 1437, 1317, 1112, 1092; 1H NMR (400 MHz, CDCl3) δ = 7.77–7.70 (9H, m), 7.65–7.60 (6H, m), 5.72 (2H, d, J = 3.96), 3.85 (2H, q, J = 7.0), 1.09 (3H, t, J = 7.0); 13C NMR (100 MHz, CDCl3) δ = 135.3, 135.3, 134.0 (3C), 133.9, 132.0 (3C), 131.9, 130.4, 130.3 (3C), 128.5, 128.4 (3C), 116.5, 64.21, 14.93; 31P-NMR (CDCl3): δ 25.77; HRMS +ESI calculated for C21H22OP: 321.1403; found 321.1404.

Benzoxymethyltriphenylphosphonium iodide (2d)

Yellow thick oil, yield = 87%, IR υ (cm−1) = 681, 734, 1103, 1305, 1425, 2767. 1H-NMR (300 MHz, MeOD): δ ppm. 7.82–7.76 (3H, m, CH aromatic), 7.75–7.71 (3H, m, CH aromatic), 7.70–7.67 (3H, m, CH aromatic), 7.66–7.62 (2H, m, CH aromatic), 7.58–7.55 (3H, m, CH aromatic), 7.48–7.45 (3H, m, CH aromatic), 7.37–7.29 (3H, m, CH aromatic), 5.72 (2H, d, J = 3, CH2), 4.97 (2H, s, CH2). 13C-NMR (75 MHz, MeOD): δ ppm. 134.57 (3 carbons), 133.60 (4 carbons), 133.19 (3 carbons), 132.33, 131.91 (4 carbons), 130.49 (4 carbons), 129.78, 129.41 (4 carbons), 97.76, 78.39. 31P (202 MHz, MeOD): δ ppm 17.55. EIMS = 383 (M+-I), 277.2 (59.6%), 262.2 (100%), 183.1 (48.4%), 108.0 (10.9%), 50.9 (9.8%).

Phenethoxymethyltriphenylphosphonium iodide (2e)

Yellowish powder, m.p = 171–173 °C, yield = 81%, IR υ (cm−1) = 690, 730, 1124, 1317, 2917. 1H-NMR (300 MHz, CDCl3): δ ppm. 7.78–7.36 (20H, m, CH aromatic), 5.45 (2H, d, J = 1.2 Hz, CH2), 4.21 (2H, t, J = 6.4, CH2), 2.75 (2H, t, J = 7.2, CH2). 13C-NMR (75 MHz, CDCl3): δ ppm. 138.43 (4 carbons), 137.98, 137.81 (2 carbons), 137.23, 136.31 (4 carbons), 136.06, 135.78, 135.23, 134.94 (3 carbons), 134.24, 129.81 (2 carbons), 129.12 (2 carbons), 117.89, 94.67, 77.78, 37.54. 31P (202 MHz, CDCl3): δ ppm 17.74. EIMS = 397 (M+-I), 277.2 (100%), 262.2 (67.6%), 183.1 (59.6%), 108.0 (13.4%), 91 (43%).

(S)-sec-Butoxymethyltriphenylphosphonium iodide (2f)

Yellowish white crystals, m.p = 58 °C, yield = 89%, \(\left[ \alpha \right]_{D}^{25}\) = − 11 (c = 0.0018, MeOH), IR: υ (cm−1) = 682, 709, 1107, 1311, 1444, 2863. 1H-NMR (300 MHz, MeOD): δ ppm. 7.93–7.88 (3H, m, CH aromatic), 7.85–7.83 (1H, m, CH aromatic), 7.82–7.78 (3H, m, CH aromatic), 7.77–7.67 (3H, m, CH aromatic), 7.64–7.63 (3H, m, CH aromatic), 7.63–7.60 (1H, m, CH aromatic), 7.56–7.54 (1H, m, CH aromatic), 5.51 (1H, dd, J = 13.5, 4.8, CH2), 5.39 (1H, dd, J = 13.5, 5.7, CH2), 3.70–3.64 (1H, m, CH), 1.60–1.43 (2H, m, CH2), 1.18 (3H, d, J = 6.0 Hz, CH3), 0.75 (3H, t, J = 7.5, CH3). 13C-NMR (75 MHz, MeOD): δ ppm. 139.32, 135.11, 134.98, 134.72, 134.46, 133.95, 133.60, 133.32, 133.00, 132.93, 132.60, 131.82, 131.27, 130.87, 130.04, 129.90, 129.83, 128.60, 94.89, 79.51, 30.51, 20.10, 10.09. 31P (202 MHz, CDCl3): δ ppm 19.01. EIMS = 349 (M+-I), 277.2 (7.7%), 262.2 (55.9%), 183.1 (100%), 167.1 (49.8%), 152.1 (14.8%), 108.0 (13.4%), 91.0 (43.9%).

Triphenyl((((2R)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl)oxy)methyl) phosphonium iodide (2g)

Lemon yellow thick oil, yield = 91%, \(\left[ \alpha \right]_{D}^{25}\) = + 55 (c = 0.004, MeOH), IR: υ (cm−1) = 684, 968, 1112, 2948. 1H-NMR (300 MHz, MeOD): δ ppm. 7.89–7.83 (4H, m, CH aromatic), 7.82–7.80 (1H, m, CH aromatic), 7.80–7.63 (4H, m, CH aromatic), 7.61–7.55 (3H, m, CH aromatic), 7.54–7.51 (3H, m, CH aromatic), 5.53 (2H, dd, J = 1.2, 4.8 Hz, CH2), 3.10 (1H, d, J = 14.1, CH), 1.67–1.53 (2H, m, CH2), 1.49–1.37 (2H, m, CH2), 1.06–1.01 (1H, m, CH), 1.06–0.96 (2H, m, CH2), 0.91 (3H, s, CH3), 0.83 (3H, s, CH3), 0.73 (3H, s, CH3). 13C-NMR (75 MHz, CDCl3): δ ppm. 135.48, 135.45 (2 carbons), 134.26, 134.18, 132.06 (3 carbons), 132.01, 131.99, 130.53 (3 carbons), 130.43, 128.56, 128.47, 116.88, 116.20, 98.49, 66.63, 49.50, 48.38, 41.18, 40.01, 31.10, 26.10, 25.80, 20.72, 19.93. 31P (202 MHz, CDCl3): δ ppm 19.46. EIMS = 429 (M+-I), 277.2 (48.4%), 262.2 (100%), 183.1 (59.6%), 108.0 (57.2%), 56 (36.3%).

((((1S,2R)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)triphenylphosphonium iodide (2h)

Light yellow semisolid, yield = 80%, \(\left[ \alpha \right]_{D}^{25}\) = + 8 (c = 0.027, MeOH), IR: υ (cm−1) = 687, 963, 1112, 2914. 1H-NMR (300 MHz, MeOD): δ ppm. 7.91–7.90 (2H, m, CH aromatic), 7.89–7.88 (1H, m, CH aromatic), 7.88–7.87 (2H, m, CH aromatic), 7.86–7.83 (4H, m, CH aromatic), 7.80–7.75 (1H, m, CH aromatic), 7.73–7.32 (1H, m, CH aromatic), 7.31–7.30 (1H, m, CH aromatic), 7.28–7.27 (1H, m, CH aromatic), 7.30–7.25 (1H, m, CH aromatic), 7.23–7.22 (1H, m, CH aromatic), 5.62 (1H, dd, J = 6.7, 3.3, CH2), 5.24 (1H, dd, J = 6.9, 2.9, CH2), 3.44 (1H, td, J = 5.7, 9.6, CH), 2.32–2.23 (1H, m, CH), 1.69–1.57 (2H, m, CH2), 1.41–1.33 (2H, m, CH2), 1.23–1.19 (2H, m, CH2), 0.95–0.91 (1H, m, CH), 0.79 (3H, d, J = 6.9, CH3), 0.75 (3H, d, J = 6.9, CH3), 0.56 (3H, d, J = 6.9, CH3). 13C-NMR (75 MHz, CDCl3): δ ppm. 135.32, 135.28, 134.32, 134.18, 134.02, 133.87, 133.61, 132.20, 132.07, 130.48, 130.32, 128.86, 128.66, 128.59, 128.50, 117.41, 116.27, 83.81, 74.16, 48.28, 46.95, 40.90, 39.42, 34.21, 31.19, 25.57, 23.41, 22.27, 16.18. 31P (202 MHz, MeOH): δ ppm 19.19. EIMS = 431 (M+-I), 277.2 (100%), 262.2 (67.6%), 183.1 (54.9%), 108.0 (10.9%), 77 (9.8%), 56 (36.3%).

Triphenyl((((2R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)oxy)methyl) phosphonium iodide (2i)

Light brown semi solid, yield = 70%, \(\left[ \alpha \right]_{D}^{25}\) = + 2.13 (c = 5 mg/15 mL MeOH), IR: υ (cm−1) = 683, 981, 1114, 2914. 1H-NMR (300 MHz, CDCl3): δ ppm. 7.89–7.83 (4H, m, CH aromatic), 7.82–7.80 (2H, m, CH aromatic), 7.77–7.71 (4H, m, CH aromatic), 7.67–7.61 (3H, m, CH aromatic), 7.57–7.51 (2H, m, CH aromatic), 5.69 (2H, dd, J = 6, 12, CH2), 3.03 (1H, dt, J = 3.9, 6.91, CH), 1.85–1.74 (2H, m, CH2), 1.65–1.64 (2H, m, CH2), 1.63–1.57 (1H, m, CH), 1.53–1.38 (2H, m), 0.90 (3H, s, CH3), 0.72 (3H, s, CH3), 0.51 (3H, s, CH3) 13C-NMR (75 MHz, CDCl3): δ ppm. 135.3, 135.3, 134.0 (3C), 133.9, 132.0, 131.9, 130.4, 130.3 (3C), 128.5 (3C), 128.4 (3C), 116.5 (d, J = 85), 76.3, 49.0, 48.6, 41.5, 41.4, 39.2, 26.2, 21.0, 20.2, 19.8; 31P (202 MHz, CDCl3): δ ppm 19.00. EIMS = 430 (M+-I), 277.2 (7.7%), 262.2 (55.9%), 183.1 (100%), 167.1 (49.8%), 152.1 (14.8%), 108.0 (13.4%), 91.0 (43.9%).

tert-Butoxymethyltriphenylphosphonium iodide (2j)

Yellowish thick oil, yield = 77%, IR: υ (cm−1) = 690, 713, 1127, 1295, 1405, 2799. 1H-NMR (400 MHz, MeOD): δ ppm. 7.91–7.90 (2H, m, CH aromatic), 7.89–7.86 (4H, m, CH aromatic), 7.83–7.75 (3H, m, CH aromatic), 7.34–7.31 (4H, m, CH aromatic), 7.25–7.23 (2H, m, CH aromatic), 5.45 (2H, dd, J = 1.6, 16.8, CH2), 0.047 (9H, s, CH3). 13C-NMR (75 MHz, CDCl3): δ ppm. 136.69 (3 carbons), 136.63, 135.39, 135.27, 134.81, 134.76 (3 carbons), 133.66, 133.13, 132.67, 131.13, 131.09, 129.79 (3 carbons), 117.69, 89.54, 28.76 (3 carbons). 31P (202 MHz, CDCl3): δ ppm 18.98. EIMS = 349 (M+-I), 277.2 (100%), 262.2 (67.6%), 201.1 (24.5%), 183.1 (54.9%), 152.1 (11.4%), 108.0 (10.9%), 77.0 (9.8%).

General method for synthesis of vinyl ethers 3ae

In a two neck round bottom flask n-BuLi (1.5 eq) was added to stirred solution of phosphonium iodide 2 (1 eq) in THF at − 78 °C and mixture was allowed to stir under argon. After 20 min solution of aldehyde (1 eq) in THF was added drop wise at the same temperature and reaction mixture was allowed to stir for further 4 h allowing the temperature to come to room temperature slowly. Reaction was monitored on TLC, after completion reaction was quenched with methanol and solvent was evaporated under reduced pressure. Products were purified on silica gel column by combinations of ethyl acetate and pet ether as eluent.

2-Ethoxyethenyl benzene (3aa′, mixture of cis and trans isomers) [38]

1H NMR (400 MHz, CDCl3) δ ppm. 8.00–7.97 (1H, m), 7.62–7.56 (1H, m), 7.50–7.46 (1 H, m), 7.32–7.25 (5H, m), 7.17–7.13 (1H, m), 7.01 (0.76H, d, J = 12.9), 6.23 (0.26H, d, J = 7.0), 5.86 (0.73H, d, J = 12.9), 5.24 (0.27H, d, J = 8.0), 4.01 (0.56H, q, J = 7.2), 3.92 (1.5 H, q, J = 7.3), 1.46–1.35 (6H, m); HRMS GC/MS calculated for C10H12O: 148.0883; found 148.0879.

1-Chloro-4[2-ethoxyethenyl]benzene (3bb′, mixture of cis and trans isomers) [39]

1H NMR (400 MHz, CDCl3) δ ppm. 7.51–7.15 (4H, m), 6.94 (0.69H, d, J = 12.0), 6.37 (0.31H, d, J = 8.0), 5.83 (0.71H, d, J = 12.0), 5.69 (0.29H, d, J = 7.4), 3.95 (0.62H, q, J = 7.4), 3.86 (1.43H, q, J = 7.2), 1.34–1.26 (6H, m); HRMS GC/MS calculated for C10H11OCl: 182.0493; found 182.0501.

1-Bromo-4[2-ethoxyethenyl]benzene (3cc′, mixture of cis and trans isomers) [42, 62]

1H NMR (400 MHz, CDCl3) δ = 7.31–7.21 (4H, m), 7.01 (0.73H, d, J = 12.8), 6.51 (0.29H, d, J = 7.1), 5.83 (0.70H, d, J = 12.8), 5.69 (0.31H, d, J = 7.3), 4.12 (1.42H, q, J = 7.2), 3.93 (0.63H, q, J = 7.5), 1.45–1.37 (6H, m); HRMS GC/MS calculated for C10H11OBr: 225.9988; found 225.9988.

1-[(1E & Z)-2-ethoxyethenyl]-4-methoxybenzene (3dd′) [42, 62]

(Mixture of cis and trans isomers) 1H NMR (400 MHz, CDCl3) δ ppm 7.57–7.15 (4H, m), 6.79 (0.63H, d, J = 13.0), 6.13 (0.37H, d, J = 8.0), 6.10 (0.64H, d, J = 12.9), 5.65 (0.38H, d, J = 7.8), 3.89 (4H, q, J = 7.5), 1.43 (6H, m). HRMS GC/MS calculated for C11H14O2: 178.0988; found 178.0991.

(E)-(2-((2-isopropyl-5-methylcyclohexyl)oxy)vinyl)benzene (3e′) [40]

Colorless oil; yield = 43%, 1H NMR (CDCl3, 400 MHz): δ ppm 7.28–7.22 (4H, m), 7.15–7.11 (1H, m), 6.92 (1H, d, J = 12.6), 5.93 (1H, d, J = 12.6), 3.62 (1H, td, J = 4.3), 2.21–2.10 (2H, m), 1.72–1.71 (1H, m), 1.69–1.68 (1H, m), 1.58–1.52 (1H, m), 1.49–1.39 (2H, m), 1.11–1.01 (2H, m), 0.95 (3H, d, J = 6.16), 0.94 (3H, d, J = 6.6), 0.82 (3H, d, J = 6.9); 13C NMR (CDCl3, 100 MHz): δ ppm 147.5, 136.7, 128.6 (2C), 125.4 (2C), 124.9, 107.0, 81.6, 47.8, 41.4, 34.3, 31.5, 25.8, 23.4, 22.1, 20.7, 16.4. HRMS GC/MS calculated for C18H26O; 258.1984, found; 258.1987.

General method for carbon homologation in aldehydes

In a two neck round bottom flask containing phosphonim iodide 2a (1 eq) in dry THF (5 mL), n-BuLi (1.5 eq) was added dropwise at − 78 °C and mixture was allowed to stir for 30 min. Solution of aldehyde (1 eq) in THF was added dropwise to the phosphorene reaction mixture and further allowed to stir for 5 h. After acidic hydrolysis, crude product was extracted with EtOAc (10 mL × 2). Combined extract was dried over Na2SO4, concentrated and purified on preparative TLC (silica gel) to obtain higher analogue of aldehydes (see Additional file 1).

General procedure for asymmetric reduction reaction

In a two-neck round bottom flask, acetophenone (1.5 mmol), NaBH4 (2.25 mmol) along with iodide salt 2g (10 mol%) was taken in methanol (5 mL). Reaction mixture was stirred for 2 h at room temperature. The reaction progress was monitored by TLC and after completion; the mixture was quenched with water and extracted EtOAc (2 × 3 mL). Combined organic layer was dried over MgSO4 and the solvent was evaporated under reduced pressure to afford the corresponding (R)-1-phenylethanol (92% yield, 4% ee). Enantiomeric excess (ee) was calculated on HPLC using chiral cellulose OD-H column, hexane/i-PrOH, 95:5, flow rate 1 mL/min (see Additional file 1).

Notes

Authors’ contributions

HYG designed and supervised the project and wrote the paper. ZMC performed experiments and assist in manuscript preparation. JHZ guided in data interpretation and reaction mechanism. SY solved X-ray structure. MIC provided instrumental facilities. All authors read and approved the final manuscript.

Acknowledgements

Authors are obliged to Pakistan Science Foundation (PSF) Islamabad for support of this research project (P-US/Chem 427). We are also grateful to HEJ Research institute of Chemistry, ICCBS Karachi for providing analytical facilities.

Availability of data

CCDC. 1537362 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033; or deposit@ccdc.cam.ac.uk). General procedure and spectral data of substrates bis-alkoxy methanes (1) and specimen NMR spectra of α-alkoxymethyl phosphonium iodides (2) and vinyl ethers (3) are given in Additional file 1.

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Not applicable.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary material

13065_2018_421_MOESM1_ESM.docx (71 kb)
Additional file 1. General method for synthesis of Bis-alkoxy methanes.
13065_2018_421_MOESM2_ESM.docx (26 kb)
Additional file 2. Carbon Homologation in aldehydes.
13065_2018_421_MOESM3_ESM.docx (27 kb)
Additional file 3. Asymmetric reduction of acetophenone.
13065_2018_421_MOESM4_ESM.docx (67 kb)
Additional file 4. Crystallography data for(S)-sec-Butoxymethyltriphenylphosphonium iodide.
13065_2018_421_MOESM5_ESM.docx (931 kb)
Additional file 5. Specimen NMR Spectra of alkoxymethyltriphenylphosphonium iodides.
13065_2018_421_MOESM6_ESM.docx (126 kb)
Additional file 6. Specimen NMR Spectrum of vinyl ether.

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Authors and Affiliations

  1. 1.Department of ChemistryUniversity of SargodhaSargodhaPakistan
  2. 2.Department of ChemistryUniversity of SheffieldSheffieldUK
  3. 3.Department of ChemistryQuaid-i-Azam UniversityIslamabadPakistan
  4. 4.H.E.J Research Institute of Chemistry, ICCBSUniversity of KarachiKarachiPakistan

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