3-Vinyl-2,5-dihydrofuran Derivatives via Enyne Metathesis

Abstract

Acyclic enynes having the alkyne moiety directly ­connected to the asymmetric carbon atom of an acetal were obtained in two steps. These reactive substrates were then subjected to ruthenium-catalyzed enyne metathesis to produce (5-ethoxy-4-­vinyl-2,5-dihydrofuran-2-yl)methanol derivatives in racemic and enantiomerically pure form. These products are useful glycosyl ­donors for the preparation of d4T analogues.

enyne - metathesis - carbohydrate - cyclization - furan

References and Notes

<A NAME="RG06807ST-1">1</A> Len C. Mackenzie G. Tetrahedron  2006,  62:  9085 

<A NAME="RG06807ST-2A">2a</A> Len C. Postel D. Curr. Org. Synth.  2006,  3:  261 

<A NAME="RG06807ST-2B">2b</A> Lin TS. Schinazi RF. Prusoff WH. Biochem. Pharmacol.  1987,  36:  2713 

<A NAME="RG06807ST-2C">2c</A> Balzarini J. Van Aerschot A. Herdewijn P. De Clercq E. Biochem. Pharmacol.  1989,  38:  869 

<A NAME="RG06807ST-3A">3a</A> Ouma S. Kumamoto H. Kawato M. Tanaka H. Tetrahedron  2002,  58:  2497 

<A NAME="RG06807ST-3B">3b</A> Kumamoto H. Tanaka H. J. Org. Chem.  2002,  67:  3541 

<A NAME="RG06807ST-3C">3c</A> Haraguchi K. Itoh Y. Tanaka H. Miyasaka T. Tetrahedron  1993,  49:  1371 

<A NAME="RG06807ST-3D">3d</A> Schmalz HG. Hebler E. Bats JW. Durner G. Tetrahedron Lett.  1994,  35:  4543 

<A NAME="RG06807ST-3E">3e</A> Hebler E. Schmalz HG. Durner G. Tetrahedron Lett.  1994,  35:  4547 

<A NAME="RG06807ST-3F">3f</A> Schlawe D. Majdalani A. Velcicky J. Hebler E. Wieder T. Prokop A. Schmalz HG. Angew. Chem. Int. Ed.  2004,  43:  1731 

<A NAME="RG06807ST-4A">4a</A> Ewing DF. Fahmi NE. Len C. Mackenzie G. Ronco G. Villa P. Shaw G. Nucleosides Nucleotides  1999,  18:  2613 

<A NAME="RG06807ST-4B">4b</A> Ewing DF. Fahmi NE. Len C. Mackenzie G. Pranzo A. J. Chem. Soc., Perkin Trans. 1  2000,  3561 

<A NAME="RG06807ST-4C">4c</A> Belloli E. Len C. Mackenzie G. Ronco G. Bonte JP. Vaccher C. J. Chromatogr., A  2001,  943:  91 

<A NAME="RG06807ST-4D">4d</A> Ewing DF. Len C. Mackenzie G. Ronco G. Villa P. Tetrahedron: Asymmetry  2000,  11:  4995 

<A NAME="RG06807ST-4E">4e</A> Selouane A. Vaccher C. Villa P. Postel D. Len C. Tetrahedron: Asymmetry  2002,  13:  407 

<A NAME="RG06807ST-4F">4f</A> Pilard S. Riboul D. Glacon V. Moitessier N. Chapleur Y. Postel D. Len C. Tetrahedron: Asymmetry  2002,  13:  529 

<A NAME="RG06807ST-4G">4g</A> Egron D. Perigaud C. Gosselin G. Aubertin AM. Faraj A. Selouane A. Postel D. Len C. Bioorg. Med. Chem. Lett.  2003,  13:  4473 

<A NAME="RG06807ST-5A">5a</A> Nicolaou KC. Bulger PG. Sarlah D. Angew. Chem. Int. Ed.  2005,  44:  4490 

<A NAME="RG06807ST-5B">5b</A> Trnka TM. Grubbs RH. Acc. Chem. Res.  2001,  34:  18 

<A NAME="RG06807ST-6A">6a</A> Poulsen CS. Madsen R. Synthesis  2003,  1 

<A NAME="RG06807ST-6B">6b</A> Diver ST. Giessert AJ. Chem. Rev.  2004,  104:  1317 

<A NAME="RG06807ST-6C">6c</A> Kinoshita A. Mori M. J. Org. Chem.  1996,  61:  8356 

<A NAME="RG06807ST-6D">6d</A> Mori M. Adv. Synth. Catal.  2007,  349:  121 

<A NAME="RG06807ST-7A">7a</A> Poulsen CS. Madsen R. J. Org. Chem.  2002,  67:  4441 

<A NAME="RG06807ST-7B">7b</A> Marco-Contelles J. Arroyo N. Ruiz-Caro J. Synlett  2001,  652 

<A NAME="RG06807ST-7C">7c</A> Boyer FD. Hanna I. Ricard L. Org. Lett.  2001,  3:  3095 

<A NAME="RG06807ST-7D">7d</A> Leeuwenburgh MA. Appeldoorn CCM. van Hooft PAV. Overkleeft HS. van der Marel GA. van Boom JH. Eur. J. Org. Chem.  2000,  873 

<A NAME="RG06807ST-7E">7e</A> Clark JS. Hamelin O. Angew. Chem. Int. Ed.  2000,  39:  372 

<A NAME="RG06807ST-7F">7f</A> Leeuwenburgh MA. Kulker C. Duynstee HI. Overkleeft HS. van der Marel GA. van Boom JH. Tetrahedron  1999,  55:  8253 

<A NAME="RG06807ST-7G">7g</A> Dohlem F. Lievre C. Demailly G. Eur. J. Org. Chem.  2003,  2336 

<A NAME="RG06807ST-8">8</A> Mori M. Sakakira N. Kinoshita A. J. Org. Chem.  1998,  63:  6082 

<A NAME="RG06807ST-9A">9a</A> Kinoshita A. Sakakibara N. Mori M. J. Am. Chem. Soc.  1997,  119:  12388 

<A NAME="RG06807ST-9B">9b</A> Kinoshita A. Sakakibara N. Mori M. Tetrahedron  1999,  8155 

<A NAME="RG06807ST-9C">9c</A> Smulik JA. Diver ST. J. Org. Chem.  2000,  65:  1788 

<A NAME="RG06807ST-9D">9d</A> Mori M. Tonogaki K. Nishiguchi N. J. Org. Chem.  2002,  67:  224 

<A NAME="RG06807ST-10">10</A> Lloyd-Jones GC. Margue RG. de Vries JG. Angew. Chem. Int. Ed.  2005,  44:  7442 

<A NAME="RG06807ST-11">11</A> Fürstner A. Langemann K. J. Am. Chem. Soc.  1997,  119:  9130 

<A NAME="RG06807ST-12">12</A>

RCEYM Reaction of rac -15 and rac -16 - Typical Procedure
The ruthenium catalyst 5 (3% mol) was dissolved in CH₂Cl₂ (26 mL) and ethylene gas was passed through the solution for 20 min. The enyne mixture of rac-15 and rac-16 (400 mg, 0.98 mmol) in CH₂Cl₂ (12 mL) was then added and the mixture was stirred under ethylene at 20 °C during 5 d. The volatiles were eliminated under reduced pressure and the residue was purified by flash chromatography (5% EtOAc in hexane) to give rac-cis-22 (100 mg, 25%) and rac-trans-22 (100 mg, 25%) in order of fractions eluted.

<A NAME="RG06807ST-13A">13a</A> Hansen EC. Lee D. J. Am. Chem. Soc.  2003,  125:  9582 

<A NAME="RG06807ST-13B">13b</A> Hansen EC. Lee D. J. Am. Chem. Soc.  2004,  126:  15074 

<A NAME="RG06807ST-14">14</A>

Selected physico-chemical data for compound cis-12: R _f = 0.50 (5% EtOAc-hexane). ¹H NMR (300 MHz, CDCl₃): δ = 7.71 (m, 4 H, Ph), 7.45 (m, 6 H, Ph), 6.48 (dd, 1 H, J = 12, 18 Hz, =CH), 6.18 (s, 1 H, H³), 5.87 (s, 1 H, H⁵), 5.46 (d, 1 H, J = 18 Hz, =CH), 5.23 (d, 1 H, J = 12 Hz, =CH), 4.80 (m, 1 H, J = 1 Hz, H²), 3.68 (m, 4 H, OCH ₂CH₃, CH₂OSi), 1.23 (t, 3 H, J = 8 Hz, CH₃), 1.06 (s, 9 H, 3 CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 138.9 (C⁴), 136.0 (Ph), 135.9 (Ph), 133.9 (C³), 133.8 (Ph), 130.4 (=CH), 128.1 (Ph), 118.0 (=CH₂), 107.6 (C⁵), 85.7 (C²), 67.6 (CH₂OSi), 62.6 (OCH₂), 27.2 (CH₃ of t-Bu), 19.6 (Cq of t-Bu), 15.8 (CH₃) ppm. ESI-HRMS: m/z calcd [M + Na⁺]: 431.2018; found: 431.2034.

<A NAME="RG06807ST-15">15</A>

Selected physico-chemical data for compound trans-12: R _f = 0.20 (5% MeOH-CH₂Cl₂). ¹H NMR (300 MHz, CDCl₃): δ = 7.65 (m, 4 H, Ph), 7.38 (m, 6 H, Ph), 6.43 (m, 1 H, J = 12, 18Hz, =CH), 5.98 (s, 1 H, H³), 5.96 (d, 1 H, J = 4 Hz, H⁵), 5.43 (d, 1 H, J = 18, =CH), 5.24 (d, 1 H, J = 12 Hz, =CH), 4.90 (m, 1 H, H²), 3.72 (m, 4 H, OCH ₂CH₃, CH₂OSi), 1.26 (t, 3 H, J = 8 Hz, CH₃), 1.04 (s, 9 H, 3 CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 138.8 (C⁴), 136.0 (Ph), 133.9 (Ph), 130.6 (C³), 130.0 (Ph), 129.0 (=CH), 128.1 (Ph), 118.0 (=CH₂), 107.6 (C⁵), 85.6 (C²), 66.6 (CH₂OSi), 62.1 (OCH₂), 27.2 (CH₃ of t-Bu), 19.6 (Cq of t-Bu), 15.8 (CH₃). ESI-HRMS: m/z calcd [M + Na⁺]: 431.2018; found: 431.2025.

<A NAME="RG06807ST-16">16</A> Barfield M. Spear RJ. Sternhell S. J. Am. Chem. Soc.  1975,  97:  5160