Efficient Synthesis of (E)-3-Alkylidene-2(3H)-furanones from 3-(1-Hydroxy­alkyl)-2-silyloxyfurans

John Boukouvalas; Olivier Marion

doi:10.1055/s-2006-944202

LETTER

Efficient Synthesis of (E)-3-Alkylidene-2(3H)-furanones from 3-(1-Hydroxyalkyl)-2-silyloxyfurans

John Boukouvalas*, Olivier Marion
Département de Chimie, Université Laval, Quebec City, Quebec G1K 7P4, Canada
Fax: +1(418)6567916; e-Mail: john.boukouvalas@chm.ulaval.ca;

Abstract

All articles of this category

Abstract

Several unsubstituted (E)-3-alkylmethylidene- and (E)-3-(arylmethylidene)-2(3H)-furanones have been synthesized in highly stereoselective fashion by mesylation-elimination of 3-(1-hydoxyalkyl)-2-silyloxyfurans. The latter were prepared from 2-triisopropylsilyloxy-3-bromofuran by halogen-lithium exchange and reaction of the in situ generated 3-lithiated silyloxyfuran with aldehydes.

Key words

2-silyloxyfurans - bromination - lithiation - lactones - stereoselectivity

Full Text

References

References and Notes

<A NAME="RS01506ST-1A">1a</A> Okabe T. Yoshida E. Chieda S. Endo K. Kamiya S. Osada K. Tanaka S. Okura A. Suda H. J. Antibiotics 1994, 47: 289

<A NAME="RS01506ST-1B">1b</A> Tanaka S. Okabe T. Nakajima S. Yoshida E. Suda H. J. Antibiotics 1994, 47: 294

<A NAME="RS01506ST-1C">1c</A> Tanaka S. Okabe T. Nakajima S. Yoshida E. Morishima H. J. Antibiotics 1994, 47: 297

<A NAME="RS01506ST-2A">2a</A> Chang RS. Ding L. Gai-Qing C. Qi-Choa P. Ze-Lin Z. Smith KM. Proc. Soc. Exp. Biol. Med. 1991, 197: 59

<A NAME="RS01506ST-2B">2b</A> Basak A. Cooper S. Roberge AG. Banik UK. Chrétien M. Seidah NG. Biochem. J. 1999, 338: 107

<A NAME="RS01506ST-2C">2c</A> Basak A. Zhong M. Munzer JS. Chrétien M. Seidah NG. Biochem. J. 2001, 353: 537

<A NAME="RS01506ST-3A">3a</A> Kitagawa I. Simanjuntak P. Hori K. Nagami N. Mahmud T. Shibuya H. Kobayashi M. Chem. Pharm. Bull. 1994, 42: 1050

The alkylidene geometry of peronemin D₁ has not been assigned.

<A NAME="RS01506ST-4">4</A> Yadav RD. Kataky JCS. Mathur RK. Indian J. Chem., Sect B: Org. Chem. Incl. Med. Chem. 1999, 38: 248

<A NAME="RS01506ST-5">5</A> Janeki T. Blaszczyk E. Studzian K. Janecka A. Krajewska U. Rózalski M. J. Med. Chem. 2005, 48: 3516 ; and references therein

<A NAME="RS01506ST-6">6</A> Rao YS. Chem. Rev. 1976, 76: 625

<A NAME="RS01506ST-7">7</A> Shanmugasundaram M. Raghunathan R. Malar EJP. Heteroat. Chem. 1998, 9: 517

<A NAME="RS01506ST-8">8</A> Rischmann M. Mues R. Geiger H. Laas HJ. Eicher T. Phytochemistry 1989, 28: 867

<A NAME="RS01506ST-9">9</A> Egorova AY. Russ. Chem. Bull., Int. Ed. 2002, 51: 183

<A NAME="RS01506ST-10">10</A> Khan RH. Rastogi RC. J. Chem. Res., Synop. 1991, 260

<A NAME="RS01506ST-11A">11a</A> Shurov SN. Zhikina IA. Podvintsev IB. Russ. J. Org. Chem. 2002, 38: 862

<A NAME="RS01506ST-11B">11b</A> See also: Shurov SN. Zhikina IA. Russ. J. Gen. Chem. 2000, 70: 1779

<A NAME="RS01506ST-12">12</A> Nair V. Bindu S. Sreekumar V. Rath NP. Org. Lett. 2003, 5: 665

<A NAME="RS01506ST-13A">13a</A> Huang Y. Alper H. J. Org. Chem. 1991, 56: 4534

<A NAME="RS01506ST-13B">13b</A> See also: El Ali B. Alper H. Synlett 2000, 161

<A NAME="RS01506ST-14">14</A> Rossi R. Bellina F. Bechini C. Mannina L. Vergamini P. Tetrahedron 1998, 54: 135

<A NAME="RS01506ST-15">15</A> Lim S.-G. Kwon B.-I. Choi M.-G. Jun C.-H. Synlett 2005, 1113

<A NAME="RS01506ST-16A">16a</A> Sigman MS. Kerr CE. Eaton BE. J. Am. Chem. Soc. 1993, 115: 7545

<A NAME="RS01506ST-16B">16b</A> Trifonov LS. Orahovats AS. Linden A. Heimgartner H. Helv. Chim. Acta 1992, 75: 1872

<A NAME="RS01506ST-17A">17a</A> Ochoa de Echagüen C. Ortuño RM. Tetrahedron 1994, 50: 12457

<A NAME="RS01506ST-17B">17b</A> Grossmann G. Poncioni M. Bornand M. Jolivet B. Neuburger M. Séquin U. Tetrahedron 2003, 59: 3237

<A NAME="RS01506ST-17C">17c</A> Posner GH. Afarinkia K. Dai H. Org. Synth. 1995, 73: 231

<A NAME="RS01506ST-18A">18a</A> Bromofuranone 9 has been previously prepared in three steps from 2,5-dimethoxy-2,5-dihydrofuran: Bella M. Piancatelli G. Squarcia A. Tetrahedron 2001, 57: 4429 ; and references therein

<A NAME="RS01506ST-18B">18b</A> See also: Vaz B. Alvarez R. Brückner R. de Lera AR. Org. Lett. 2005, 7: 545

<A NAME="RS01506ST-19">19</A> Boukouvalas J. Lachance N. Synlett 1998, 31

For the preparation and addition of metallated silyloxyfurans to carbonyl compounds, see:

<A NAME="RS01506ST-20A">20a</A> Boukouvalas J. Cheng Y.-X. Robichaud J. J. Org. Chem. 1998, 63: 228

<A NAME="RS01506ST-20B">20b</A> Kanoh N. Ishihara J. Yamamoto Y. Murai A. Synthesis 2000, 1878

<A NAME="RS01506ST-20C">20c</A> Xin Z. Zheng GZ. Stewart AO. Synlett 2000, 1324

<A NAME="RS01506ST-20D">20d</A> Sibi MP. He L. Org. Lett. 2004, 6: 1749

<A NAME="RS01506ST-20E">20e</A> Paintner FF. Allmendinger L. Bauschke G. Synlett 2005, 2735

Data for 10: colorless liquid. ¹H NMR (400 MHz, CDCl₃): δ = 1.10 (18 H, d, J = 7.2 Hz), 1.29 (3 H, m), 6.27 (1 H, d, J = 2.4 Hz), 6.80 (1 H, d, J = 2.4 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 12.3, 17.4, 73.3, 114.1, 131.7, 153.4. HRMS: m/z calcd: 318.0651 [M⁺]; found: 318.0656.

Typical Procedure.
To a solution of bromofuran 10 (0.720 g, 2.26 mmol) in anhyd THF (30 mL) stirred at -78 °C under nitrogen was added n-BuLi (2.5 M in hexane, 1.08 mL, 2.49 mmol). After 30 min at -78 °C, a solution of freshly distilled n-hexanal (0.450 g, 4.53 mmol) in THF (10 mL) was added dropwise and the mixture was stirred at -78 °C for 2 h. Then, H₂O was added (150 mL) and the solution was extracted twice with EtOAc. The combined extracts were washed with H₂O, aq sat. NaCl, dried (Na₂SO₄) and concentrated in vacuo. Purification by flash chromatography (95:5:1, hexane-Et₂O-Et₃N) afforded furylcarbinol 11a (0.708 g, 92%). All furylcarbinols 11a-j were obtained as oils and characterized by ¹H NMR, ¹³C NMR, and HRMS; data for representative compounds are provided below.
Data for 11a: ¹H NMR (300 MHz, CDCl₃): δ = 0.87-1.80 (32 H, m), 2.17 (1 H, m), 4.60 (1 H, m), 6.27 (1 H, d, J = 1.9 Hz), 6.76 (1 H, d, J = 1.9 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 12.0, 14.0, 17.7, 22.7, 25.6, 31.7, 37.4, 65.9, 99.7, 109.7, 131.3, 152.3. HRMS: m/z calcd: 297.1886 [M - C₃H₇]⁺; found: 297.1891.
Data for 11e: ¹H NMR (400 MHz, CDCl₃): δ = 1.07 (18 H, m), 1.27 (3 H, m), 2.05 (1 H, d, J = 3.0 Hz), 5.75 (1 H, d, J = 3.0 Hz), 6.12 (1 H, d, J = 2.4 Hz), 6.71 (1 H, d, J = 2.4 Hz), 7.30 (5 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 12.5, 17.8, 67.9, 99.9, 110.5, 126.2, 127.3, 128.5, 131.6, 143.8, 153.5. HRMS: m/z calcd: 346.1964 [M⁺]; found: 346.1961.
Data for 11f: ¹H NMR (400 MHz, CDCl₃): δ = 1.08 (18 H, m), 1.27 (3 H, m), 2.17 (1 H, d, J = 3.6 Hz), 3.73 (3 H, s), 5.71 (1 H, s), 6.16 (1 H, d, J = 2.2 Hz), 6.71 (1 H, d, J = 2.2 Hz), 6.85 (2 H, d, J = 8.4 Hz), 7.31 (2 H, d, J = 8.4 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 12.5, 17.8, 55.4, 67.6, 100.1, 110.6, 113.8, 127.5, 131.6, 136.2, 153.3, 158.9. HRMS: m/z calcd: 333.1522 [M - C₃H₇ ⁺]; found: 333.1518.
Data for 11g: ¹H NMR (400 MHz, CDCl₃): δ = 1.08 (18 H, m), 1.26 (3 H, m), 2.42 (1 H, br s), 5.81 (1 H, s), 6.04 (1 H, d, J = 2.2 Hz), 6.71 (1 H, d, J = 2.2 Hz), 7.54 (2 H, d, J = 9.1 Hz), 8.14 (2 H, d, J = 9.1 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 12.5, 17.8, 67.0, 98.9, 110.0, 123.7, 126.9, 132.1, 147.2, 151.3, 153.8. HRMS: m/z calcd: 392.1893 [MH⁺]; found: 392.1890.

The E-stereochemistry of compounds 5a-j was determined by NOESY experiments. The Z-isomers of 5a-c are clearly distinguished by ¹H NMR from their E-isomers by the upfield shift of the three olefin protons (Δδ ca. 0.1-0.3 ppm).

Typical Procedure.
To a solution of furylcarbinol 11e (0.190 g, 0.55 mmol) in anhyd CH₂Cl₂ (5 mL) stirred at -78 °C under nitrogen was added Et₃N (0.056 g, 0.55 mmol) and MsCl (0.063 g, 0.55 mmol). The mixture was stirred at -78 °C for 1 h and TBAF (1.0 M in THF, 0.55 mL, 0.55 mmol) was added. The mixture was slowly warmed to r.t. with stirring over 1 h. Purification by column chromatography (4:1, hexane-Et₂O) provided furanone 5e (0.088 g, 93%).
Data for 5a: colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 0.86 (3 H, t, J = 7.1 Hz), 1.28 (4 H, m), 1.48 (2 H, m), 2.31 (2 H, m), 6.12 (1 H, dd, J = 4.0, 1.0 Hz), 6.74 (1 H, m), 6.94 (1 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 22.6, 28.3, 30.7, 31.6, 105.4, 126.2, 144.1, 145.4, 168.3. HRMS: m/z calcd: 166.0994 [M⁺]; found: 166.0991.
Data for 5b: colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 0.95 (6 H, d, J = 6.8 Hz), 1.85 (1 H, m), 2.24 (2 H, t, J = 6.4 Hz), 6.15 (1 H, dd, J = 3.6, 0.8 Hz), 6.78 (1 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 22.7, 38.6, 39.7, 105.5, 126.9, 143.0, 145.6, 168.3. HRMS: m/z calcd: 152.0837 [M⁺]; found: 152.0842.
Data for 5c: colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 1.11 (6 H, d, J = 6.4 Hz), 2.70 (1 H, m), 6.15 (1 H, dd, J = 3.6, 0.8 Hz), 6.61 (1 H, dq, J = 10.0, 0.8 Hz), 6.97 (1 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 22.2, 30.5, 105.4, 124.1, 145.4, 150.0, 168.8. HRMS: m/z calcd: 138.0681 [M⁺]; found: 138.0676.
Data for 5d: colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 1.22 (9 H, s), 6.34 (1 H, dd, 3.8, 0.8 Hz), 6.77 (1 H, dd, J = 1.9, 0.8 Hz), 6.99 (1 H, dd, J = 3.8, 1.9 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 29.9, 35.6, 105.8, 122.4, 145.4, 153.7, 169.9. HRMS: m/z calcd: 152.0837 [M⁺]; found: 152.0833.
Data for 5e: yellow solid, mp 190-192 °C. ¹H NMR (400 MHz, CDCl₃): δ = 6.58 (1 H, dd, J = 3.6, 1.0 Hz), 7.12 (1 H, dd, J = 3.6, 2.0 Hz), 7.43 (4 H, m), 7.53 (2 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 106.4, 123.3, 129.3, 130.4, 130.8, 134.8, 137.9, 147.5, 169.6. HRMS: m/z calcd: 172.0524 [M⁺]; found: 172.0519.
Data for 5f: yellow solid, mp 129-130 °C. ¹H NMR (400 MHz, CDCl₃): δ = 3.83 (3 H, s), 6.55 (1 H, dd, J = 3.4, 0.8 Hz), 6.92 (2 H, dd, J = 7.0, 1.8 Hz), 7.08 (1 H, dd, J = 3.4, 2.0 Hz), 7.37 (1 H, m), 7.51 (2 H, dd, J = 7.0, 2.0 Hz).
¹³C NMR (100 MHz, CDCl₃): δ = 55.7, 106.4, 114.9, 120.7, 127.6, 132.4, 137.8, 146.5, 161.9, 170.1. HRMS: m/z calcd: 202.0630 [M⁺]; found: 202.0624.
Data for 5g: yellow solid, mp 212-213 °C. ¹H NMR (400 MHz, CDCl₃): δ = 6.55 (1 H, dd, J = 3.7, 1.0 Hz), 7.25 (1 H, dd, J = 3.7, 1.6 Hz), 7.44 (1 H, m), 7.68 (2 H, dd, J = 6.9, 1.6 Hz), 8.28 (2 H, dd, J = 6.9, 1.6 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 106.0, 124.5, 126.7, 130.7 (2×), 134.1, 140.8, 149.8, 168.5. Anal. Calcd for C₁₂H₇NO₄: C, 60.83; H, 3.25; N, 6.45. Found: C, 60.56; H, 3.05; N, 6.38.
Data for 5h: yellow solid, mp 92-93 °C. ¹H NMR (400 MHz, CDCl₃): δ = 6.55 (1 H, dd, J = 3.5, 0.8 Hz), 7.17 (1 H, dd, J = 3.5, 1.8), 7.40 (4 H, m), 7.51 (1 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 106.2, 124.6, 128.5, 129.8, 130.6 (2×), 135.3, 135.9, 136.5, 148.3, 169.1. HRMS: m/z calcd: 206.0135 [M⁺]; found: 206.0129.
Data for 5i: yellow solid, mp 222-223 °C. ¹H NMR (400 MHz, CDCl₃): δ = 6.63 (1 H, dd, J = 3.4, 0.8 Hz), 7.15 (1 H, dd, J = 3.4, 1.8 Hz), 7.44 (4 H, m), 7.64 (6 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 106.5, 123.1, 127.3, 127.9, 128.4, 129.2, 131.0, 133.8, 137.4, 140.0, 143.5, 147.4, 169.7. Anal. Calcd for C₁₇H₁₂O₂: C, 82.24; H, 4.87. Found: C, 81.97; H, 4.66.
Data for 5j: yellow solid, mp 191-192 °C (dec.). ¹H NMR (400 MHz, CDCl₃): δ = 6.55 (1 H, dd, J = 3.4, 1.6 Hz), 6.80 (2 H, m), 7.07 (1 H, dd, J = 3.4, 1.6 Hz), 7.12 (1 H, m), 7.63 (1 H, d, J = 1.6 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 108.1, 113.4, 119.3, 120.3, 122.1, 146.0, 146.8, 151.9, 169.9. HRMS: m/z calcd: 162.0317 [M⁺]; found: 162.0322.

<A NAME="RS01506ST-25">25</A> Hoffmann RW. Chem. Rev. 1989, 89: 1841

<A NAME="RS01506ST-26A">26a</A> Wollenberg RH. Tetrahedron Lett. 1980, 21: 3139

<A NAME="RS01506ST-26B">26b</A> Tanaka K. Terauchi M. Kaji A. Bull. Chem. Soc. Jpn. 1982, 55: 3935

<A NAME="RS01506ST-26C">26c</A> Chen S.-Y. Joullié MM. Tetrahedron Lett. 1983, 24: 5027

For alternative routes to 3-alkenylfuranones, see:

<A NAME="RS01506ST-27A">27a</A> Yu W.-Y. Alper H. J. Org. Chem. 1997, 62: 5684

<A NAME="RS01506ST-27B">27b</A> Dixon DJ. Ley SV. Reynolds DJ. Angew. Chem. Int. Ed. 2000, 39: 3622

<A NAME="RS01506ST-27C">27c</A> Johansson M. Köpcke B. Anke H. Sterner O. Tetrahedron 2002, 58: 2523

<A NAME="RS01506ST-27D">27d</A> Oh CH. Park SJ. Ryu JH. Gupta AK. Tetrahedron Lett. 2004, 45: 7039

Efficient Synthesis of (E)-3-Alkylidene-2(3H)-furanones from 3-(1-Hydroxy­alkyl)-2-silyloxyfurans

Efficient Synthesis of (E)-3-Alkylidene-2(3H)-furanones from 3-(1-Hydroxyalkyl)-2-silyloxyfurans