An efficient one-pot multicomponent synthesis of 3,4-dihydropyrimidine-2-(1H)-ones/thiones/imines via a Lewis base catalyzed Biginelli-type reaction under solvent-free conditions

1 Introduction

The Biginelli reaction (Kappe, 1993) is a well-known, simple and straightforward procedure for the synthesis of 3,4-dihydropyrimidinones (3,4-DHPMs) by the three-component condensation of an aliphatic or aromatic aldehyde, β-ketoester and an urea. The original reaction was first reported by Biginelli (1893) and was catalyzed by mineral acids. This simple procedure has been successful in a number of Biginelli reactions involving substrates lacking sterically demanded groups. By the three-component Biginelli condensation many 3,4-DHPMs have been synthesized. These non-planar DHPMs represent a heterocyclic system of remarkable pharmacological efficiency, including antiviral, antibacterial and anti-inflammatory activities (Kappe, 1993). More recently DHPMs have emerged as the integral backbones of several calcium channel modulators, anti-hypertensive agents and α-1a-antagonists (Atwal et al., 1989, 1991; Rovnyak et al., 1992; Kappe et al., 1997). Apart from synthetic DHPMs derivatives, some alkaloids are isolated from marine sources with interesting biological activities containing the dihydropyrimidine-5-carboxylate core (Snider and Shi, 1993). 3,4-DHPMs are also used as starting material for the synthesis of so called ‘superstatin’ rosuvastatin selective and competitive inhibitor of HMG-CoA reductase (Carswell et al., 2002), the enzyme responsible for the biosynthesis of cholesterol. Moreover, the 3,4-DHPM motif is present in many products isolated from natural material such as several species of sponges.

More recently, advances in the involvement of newer catalytic systems involvement in solid phase, parallel and other combinatorial synthetic approaches contributed toward the expansion of Biginelli cyclocondensation applications. The three-component cyclocondensation reaction constituting aldehyde, β-ketoester, and urea in an acidic medium was refluxed using ethanolic/methanolic HCl in the classical synthesis while other solvent-cum-acidic catalytic systems such as THF–HCl and dioxane–HCl were also employed with H₂SO₄ as a replaceable acidic source in later developments. The major drawbacks associated with acid-catalyzed reactions were lower yields (Kappe, 1993) (from 26% to 60%), particularly for tri- and tetra-substituted aldehydes of aromatic and aliphatic origins as well as extended reaction times from 24 to 36 h. The increasing interest in this class of compounds led to the development of other synthetic strategies with alternate catalysts.

Due to the importance of the Biginelli reaction products, much work on improving the yields and reaction conditions has been actively pursued. For example, Lewis acid catalysts like Mn(OAc)₃·2H₂O (Kumar et al., 2001), Cu(OTf)₂ (Paraskar et al., 2003), VCl₃ (Sabitha et al., 2003), Yb(OTf)₃ (Ma et al., 2000) and LaCl₃·7H₂O (Lu et al., 2004) have significantly improved the reaction output with reduced reaction times. The polymer-supported, resin-bound isothiourea (Kappe, 2001), poly(4-vinylpyridine-co-divinyl benzene–Cu-II) complex (Yarapathi et al., 2004), ceria/vinyl-pyrimidine polymer nanocomposite (Sabitha et al., 2005), N-butyl-N,N-dimethyl-a-phenyl-ethyl ammonium bromide (Reddy et al., 2003), and various other catalysts have been successfully used for the synthesis of Biginelli products. Further, aluminum hydrogen sulfate Al(HSO₄)₃ and potassium hydrogen sulfate KHSO₄ were applied with success as a source of both protic and metallic Lewis acids (Tu et al., 2004; Khodaei et al., 2004). Several improved procedures have been reported using heteropoly acids (Amini et al., 2006; Heravi et al., 2006; Maradur and Gokavi, 2007) such as H₃PW₁₂O₄₀, H₃PMo₁₂O₄₀, H₃PMo₁₁VO₄₀ and propane phosphoric acid (Zumpe et al., 2007). On the other hand, this condensation was found to be equally effective when Lewis acids were replaced by a strong Brönsted base (KOH), but in this case the reaction involves two steps (Anatoly et al., 1998). Therefore synthesis of this type of heterocyclic compounds has been the focus of much interest from organic and medicinal chemistry. Many synthetic methods have been developed and Biginelli reaction has gained an active ongoing research.

2 Experimental

Melting points are uncorrected. IR spectra were taken on a Perkin–Elmer Joel 983 spectrometer. ¹H NMR spectra were recorded on a Bruker AM300 (300 MHz) spectrometer using TMS as the internal standard. Column chromatography employed silica gel of 100–200 mesh. Elemental analyses were measured by means of Perkin–Elmer 2400 CHN elemental analyzer flowchart. Chemicals were purchased from Lancaster or Fluka Ltd.

2.1

2.1 General procedure for the preparation of 3,4-dihydropyrimidinones / thiones / imines

A mixture of aldehyde (2 mmol), ethyl acetoacetate (2.5 mmol), urea/thiourea/guanidine (2.5 mmol) and triphenylphosphine (0.2 mmol) was heated with stirring at 100 °C for 8 h. After cooling, the reaction mixture was poured into crushed ice with stirring. The crude product was filtered, washed with cold water, dried and recrystallized from 95% ethanol or ethyl acetate to give pure products (1–18) (80–90%). All compounds were fully characterized by elemental analysis, mp, IR and ¹H NMR spectroscopy. The structures of all synthesized compounds (1–18) have been depicted in Fig. 1.

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Figure 1

General structures of compounds 1–18.

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2.1.1

2.1.1 5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (1)

IR (KBr): 3420, 3217, 2885, 1711, 1641 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.08 (t, J = 7.1 Hz, 3H, CH₃-10), 2.33 (s, 3H, CH₃-7), 3.92 (q, J = 7.1, 4.8 Hz, 2H, CH₂O-9), 5.22 (s, 1H, CH-4), 7.30–7.23 (m, 5H, Ar-H), 8.48 (s, 1H, NH-3), 9.48 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₆N₂O₃: C, 64.62; H, 6.15; N, 10.72. Found: C, 64.58; H, 6.13; N, 10.72.

2.1.2

2.1.2 5-ethoxycarbonyl-6-methyl-4-(2-hydroxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (2)

IR (KBr): 3411, 3224, 2876, 1701, 1633 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.05 (t, J = 7.1 Hz , 3H, CH₃-10), 2.24 (s, 3H, CH₃-7), 3.94 (q, J = 7.1, 4.8 Hz, 2H, CH₂O-9), 5.20 (s, 1H, CH-4), 4.10 (d, 1H, Ar-OH), 7.40–6.8 (m, 4H, Ar-H), 8.40 (s,1H, NH-3), 9.20 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₆N₂O₄: C, 60.86; H, 5.80; N, 10.14. Found: C, 60.88; H, 5.78; N, 10.18.

2.1.3

2.1.3 5-ethoxycarbonyl-6-methyl-4-(2-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (3)

IR (KBr): 3404, 3236, 2866, 1718, 1628 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.08 (t, J = 7.1 Hz , 3H, CH₃-10), 2.22 (s, 3H, CH₃-7), 3.92 (q, J = 7.1, 4.8 Hz, 2H, CH₂O-9), 5.22 (s, 1H, CH-4), 7.30–6.9 (m, 4H, Ar-H), 8.10 (s, 1H, NH-3), 9.12 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₅ClN₂O₃: C, 57.14; H, 5.10; N, 9.52. Found: C, 57.10; H, 5.06; N, 9.56.

2.1.4

2.1.4 5-ethoxycarbonyl-6-methyl-4-(3-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (4)

IR (KBr): 3422, 3222, 2866, 1704, 1628 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.06 (t, J = 7.1 Hz , 3H, CH₃-10), 2.16 (s, 3H, CH₃-7), 3.90 (q, J = 7.1, 4.8 Hz, 2H, CH₂O-9), 5.30 (s, 1H, CH-4), 7.40–6.8 (m, 4H, Ar-H), 8.08 (s, 1H, NH-3), 9.30 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₅ClN₂O₃: C, 57.14; H, 5.10; N, 9.52. Found: C, 57.12; H, 5.08; N, 9.50.

2.1.5

2.1.5 5-ethoxycarbonyl-6-methyl-4-(3-fluorophenyl)-3,4-dihydropyrimidin-2(1H)-one (5)

IR (KBr): 3411, 3230, 2878, 1718, 1622 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.08 (t, J = 7.1 Hz , 3H, CH₃-10), 2.18 (s, 3H, CH₃-7), 3.94 (q, J = 7.1, 4.8 Hz, 2H, CH₂O-9), 5.28 (s, 1H, CH-4), 7.30–6.80 (m, 4H, Ar-H), 7.92 (s, 1H, NH-3), 9.04 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₅FN₂O₃: C, 60.43; H, 5.39; N, 10.07. Found: C, 60.39; H, 5.36; N, 10.08.

2.1.6

2.1.6 5-ethoxycarbonyl-6-methyl-4-(4-fluorophenyl)-3,4-dihydropyrimidin-2(1H)-one (6)

IR (KBr): 3418, 3220, 2866, 1700, 1628 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.08 (t, J = 7.1 Hz , 3H, CH₃-10), 2.22 (s, 3H, CH₃-7), 3.92 (q, J = 7.1, 4.8 Hz, 2H, CH₂O-9), 5.24 (s, 1H, CH-4), 7.40–6.85 (m, 4H, Ar-H), 8.18 (s, 1H, NH-3), 9.12 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₅FN₂O₃: C, 60.43; H, 5.39; N, 10.07. Found: C, 60.40; H, 5.35; N, 10.10.

2.1.7

2.1.7 5-ethoxycarbonyl-6-methyl-4-(2-chloroyphenyl)-3,4-dihydropyrimidin-2(1H)-thione (7)

IR (KBr): 3422, 3344, 1712, 1668, 1366, 1288 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.04 (t, J = 7.2 Hz, 3H, CH₃-10), 2.15 (s, 3H,CH₃-7), 4.22 (q, J = 7.2, 4.3 Hz , 2H, CH₂O-9), 4.22 (s, 1H, CH-4), 7.21–6.81 (m, 4H, Ar-H), 8.46 (s, 1H, NH-3), 9.57 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₅ClN₂O₂S: C, 54.19; H, 4.84; N, 9.03; S, 10.32. Found: C, 54.15; H, 4.80; N, 9.05; S, 10.30.

2.1.8

2.1.8 5-ethoxycarbonyl-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-thione (8)

IR (KBr): 3426, 3134, 2982, 1698, 1633, 1325, 1287 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.20 (t, J = 7.9 Hz, 3H, CH₃-10), 2.34 (s, 3H, CH₃-7), 3.88 (s, 3H, Ar-OCH₃-4′), 4.12 (q, J = 7.9, 4.6 Hz, 2H, CH₂O-9), 5.26 (s, 1H, CH-4), 6.9 (s, 1H, NH-3), 7.81–6.84 (m, 4H, Ar-H), 9.56 (s, 1H, NH-1). Anal. Calcd for C₁₅H₁₈N₂O₃S: C, 58.82; H, 5.88; N, 9.15; S, 10.45. Found: C, 58.78; H, 5.86; N, 9.16; S, 10.43.

2.1.9

2.1.9 5-ethoxycarbonyl-6-methyl-4-(2-nitrophenyl)-3,4-dihydropyrimidin-2(1H)thione (9)

IR (KBr): 3322, 3266, 2980, 1690, 1622, 1366, 1320 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.18 (t, J = 7.2 Hz, 3H, CH₃-10), 2.0 (s, 3 H, CH₃-7), 4.12 (q, J = 7.2, 4.3 Hz, 2H, CH₂O-9), 5.11 (s, 1H, CH-4), 7.4–6.8 (m, 4H, Ar-H): 7.43 (s, 1H, NH-3), 9.26 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₅N₃O₄S: C, 52.33; H, 4.67; N, 13.08; S, 9.97. Found: C, 52.30; H, 4.66; N, 13.10; S, 9.99.

2.1.10

2.1.10 5-ethoxycarbonyl-6-methyl-4-(3-nitrorophenyl)-3,4-dihydropyrimidin-2(1H)-thione (10)

IR (KBr): 3426, 3278, 2966, 1718, 1628, 1344, 1278 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.18 (t, J = 7.5 Hz, 3H, CH₃-10), 2.23 (s, 3H,CH₃-7), 4.12 (q, J = 7.4, 4.4 Hz, 2H, CH₂O-9), 4.12 (s, 1H, CH-4), 7.29–6.23 (m, 4H, Ar-H), 7.40 (s, 1H, NH-3), 9.32 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₅N₃O₄S: C, 52.33; H, 4.67; N, 13.08; S, 9.97. Found: C, 52.30; H, 4.66; N, 13.09; S, 9.98.

2.1.11

2.1.11 5-ethoxycarbonyl-6-methyl-4-(3-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-thione (11)

IR (KBr): 3418, 3146, 2958, 1700, 1622, 1318, 1278 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.20 (t, J = 7.9 Hz, 3H, CH₃-10), 2.34 (s, 3H, CH₃-7), 3.88 (s, 3H, Ar-OCH₃-4′), 4.12 (q, J = 7.9, 4.6 Hz, 2H, CH₂O-9), 5.26 (s, 1H, CH-4), 6.8 (s, 1H, NH-3), 7.81–6.84 (m, 4H, Ar-H), 9.5 (s, 1H, NH-1). Anal. Calcd for C₁₅H₁₈N₂O₃S: C, 58.82; H, 5.88; N, 9.15; S, 10.45. Found: C, 58.78; H, 5.86; N, 9.16; S, 10.44.

2.1.12

2.1.12 5-ethoxycarbonyl-6-methyl-4-(4-N,N-dimethylaminophenyl)-3,4-dihydropyrimidin-2(1H)-thione (12)

IR (KBr): 3330, 3124, 2944, 1690, 1618, 1320, 1282 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.16 (t, J = 7.9 Hz , 3H, CH₃-10), 2.40 (s, 3H, CH3-7), 5.47 (s, 1H, CH-4), 2.71 (s, 6H, N(CH₃)₂), 3.35 (q, J = 7.9, 4.4 Hz, 2H, CH₂O-9), 8.21 (s, 1H, NH-3), 9.48 (s, 1H, NH-1), 7.30–7.23 (m, 4H, Ar-H). Anal. Calcd for C₁₆H₂₁N₃O₂S: C, 60.19; H, 6.58; N, 13.16; S, 10.03. Found C, 60.16; H, 6.56; N, 13.14; S, 10.06

2.1.13

2.1.13 5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-imine (13)

IR (KBr): 3340, 3287, 2875, 1700, 1641,1330 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.09 (t, J = 7.1 Hz , 3H, CH₃-10), 2.33 (s, 3H, CH₃-7), 3.34 (s, 1H, ⚌NH-2), 4.08 (q, J = 7.1, 4.8 Hz, 2H, CH₂O-9), 5.30 (s, 1H, CH-4), 7.30–7.23 (m, 5H, Ar-H), 8.4 (s, 1H, NH-3), 9.4 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₇N₃O₂: C, 64.86; H, 6.56; N, 16.21. Found: C, 64.84; H, 6.54; N, 16.20.

2.1.14

2.1.14 5-ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-3,4-dihydropyrimidin-2(1H)-imine (14)

IR (KBr): 3222, 3120, 2978, 1692, 1650, 1344 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.09 (t, J = 7.9 Hz, 3H, CH₃-10), 2.40 (s, 3H, CH₃-7), 5.47 (s, 1H, CH-4), 1.64 (s, 3H, Ar-CH₃-4′), 3.27 (s, 1H, ⚌NH-2), 3.35 (q, J = 7.9, 4.4 Hz, 2H, CH₂O-9), 7.30–6.94 (m, 4H, Ar-H), 7.22 (s, 1H, NH-3), 9.22 (s, 1H, NH-1). Anal. Calcd for C₁₅H₁₉N₃O₂: C, 65.59; H, 6.96; N, 15.38. Found: C, 65.58; H, 6.96; N, 15.40.

2.1.15

2.1.15 5-ethoxycarbonyl-6-methyl-4-(2,3,4-trimethoxyphenyl)-3,4-dihydropyrimidin-2(1H)-imine (15)

IR (KBr): 3257, 3104, 2976, 1711, 1641, 1330 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.09 (t, J = 7.9 Hz, 3H, CH₃-10), 2.40 (s, 3H, CH₃-7), 5.47 (s, 1H, CH-4), 3.27 (s, 1H, ⚌NH-2), 3.35 (q, J = 7.9, 4.4 Hz, 2H, CH₂O-9), 3.80 (s, 3H, Ar-OCH₃-2′), 3.84 (s, 3H, Ar-OCH₃-3′), 3.70 (s, 3H, Ar-OCH₃-4′), 7.44 (s, 1H, NH-3), 7.30–7.06 (m, 2H, Ar-H), 8.88 (s, 1H, NH-1). Anal. Calcd for C₁₇H₂₃N₃O₅: C, 58.45; H, 6.59; N, 12.03. Found: C, 58.44; H, 6.58; N, 12.02.

2.1.16

2.1.16 5-ethoxycarbonyl-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-imine (16)

IR (KBr): 3371, 3134, 2975, 1698, 1641, 1322 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.09 (t, J = 7.9 Hz, 3H, CH₃-10), 2.40 (s, 3 H, CH₃-7), 5.47(s, 1H, CH-4), 3.27 (s, 1H, ⚌NH-2), 3.35 (q, J = 7.9, 4.4 Hz, 2H, CH₂O-9), 3.78 (s, 3H, Ar-OCH₃-4′), 7.33–6.98 (m, 4H, Ar-H), 7.31 (s, 1H, NH-3), 9.97 (s, 1H, NH-1). Anal. Calcd for C₁₅H₁₉N₃O₃: C, 60.17; H, 6.63; N, 13.16. Found: C, 60.21; H, 6.65; N, 13.14.

2.1.17

2.1.17 5-ethoxycarbonyl-6-methyl-4-(4-N,N-dimethylaminophenyl)-3,4-dihydropyrimidin-2(1H)-imine (17)

IR (KBr): 3319, 3114, 2965, 1690, 1650, 1318 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.09 (t, J = 7.9 Hz, 3H, CH₃-10), 2.40 (s, 3H, CH₃-7), 5.47 (s, 1H, CH-4), 3.27 (s, 1H, ⚌NH-2), 2.64 (s, 6H, N(CH₃)₂), 3.35 (q, J = 7.9, 4.4 Hz, 2H, CH₂O-9), 8.21 (s, 1H, NH-3), 9.48 (s, 1H, NH-1), 7.20–6.90 (m, 4H, Ar-H). Anal. Calcd for C₁₆H₂₂N₄O₂: C, 62.28; H, 6.57; N, 14.53. Found: C, 62.26; H, 6.54; N, 14.56.

2.1.18

2.1.18 5-ethoxycarbonyl-6-methyl-4-(3-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-imine (18)

IR (KBr): 3338, 3280, 2870, 1700, 1646, 1326 cm⁻¹: ¹H NMR (300 MHz, DMSO-d₆): δ 1.16 (t, J = 7.1 Hz , 3H, CH₃-10), 2.33 (s, 3H, CH₃-7), 3.34 (s, 1H, =NH-2), 3.90 (q, J = 7.1, 4.8 Hz, 2H, CH₂O-9), 5.30 (s, 1H, CH-4), 7.32–6.98 (m, 4H, Ar-H), 8.4 (s, 1H, NH-3), 9.4 (s, 1H, NH-1). Anal. Calcd for C₁₄H₁₆ClN₃O₂: C, 57.34; H, 5.46; N, 14.33. Found: C, 57.30; H, 5.44; N, 14.36.

3 Results and discussion

Dihydropyrimidines show a diverse range of biological activities. We are interested in studying Biginelli reaction with the aim to develop an operationally simple method for the synthesis of a large range of DHPMs. We started our study of the one-pot three-component Biginelli condensation using triphenylphosphine as the catalyst (Scheme 1), by examining the conditions for the reaction using benzaldehyde, ethylacetoacetate and urea to afford the corresponding DHPM product. We studied the reaction in different solvents including ethanol, acetonitrile, toluene, dichloromethane, cyclohexane and under solvent-free conditions at 100 °C (Table 1). The best results were obtained under solvent-free conditions (entry 6). The reaction is optimized for the amount of triphenylphosphine required (entries 7–10) and the optimum amount was found to be 10 mol%. In order to improve the yields, the reaction is performed using different quantities of reagents. The best results were obtained with a 1:1.25:1.25:0.1 ratio of benzaldehyde, ethylacetoacetate, urea, and triphenylphosphine, respectively.

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Scheme 1

General synthetic scheme of compounds 1–18.

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In order to investigate the scope of these conditions, we have undertaken the synthesis of different derivatives of 3,4-dihydropyrimidin-2(1H)-one (1–6), 3,4-dihydropyrimidin-2(1H)-thione (7–12), and 3,4-dihydropyrimidin-2(1H)-imine (13–18) from a variety of substrates from aromatic aldehydes, ethylacetoacetate (Kappe, 2001) and either urea/thiourea or guanidine in the presence of triphenylphosphine (PPh₃) as catalyst. The benzaldehyde derivatives with substitutions in the aromatic ring with 4-methyl, n-halogens (n = varying ring substitution positions), 2-hydroxy, n-methoxy, varying nitro positions and N,N-dimethylamino groups were reacted with urea, thiourea, and guanidine to furnish a series of products 1–18 (Scheme 1, Table 2).

The mechanism of the Biginelli reaction established by Kappe (1997) proposed that the key step in this cyclocondensation process should involve the formation of N-acyliminium ion intermediate. The suggested mechanism for the Biginelli reaction catalyzed by triphenylphosphine under solvent-free conditions is outlined in Scheme 2.

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Scheme 2

Suggested mechanism for the Biginelli reaction catalyzed by triphenylphosphine under solvent-free conditions. (See above-mentioned references for further information.)

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4 Conclusions

In summary, we have described a novel method for the preparation of substituted dihydropyrimidinones/thiones/imines catalyzed by triphenylphosphine (PPh₃) as Lewis base under neutral and solvent-free conditions. Moderate to good yields of the corresponding DHPMs were obtained from readily available starting materials.