Concise Synthesis of (+)-β-Benzyl γ-Butyrolactones from Butynediol

Abstract

The synthesis of optically active β-benzyl-γ-butyrolactones from butynediol via four transition metal catalysed reactions is reported. Key reactions are the hitherto unknown enantioselective hydrogenation of 2-benzyl-2-buten-1,4-diols using Ir(I)-phosphinooxazoline catalysts and the regiocontrolled oxidation of the resulting 2-benzyl-1,4-butanediols to the β-substituted butyro-lactones.

(+)-β-benzyl γ-butyrolactones - butynediol - enantioselective hydrogenation

References

<A NAME="RG30101ST-1">1</A>

New address: AVACON Internet-Service, Fürstenwalder Damm 472, d-12587 Berlin, Germany.

<A NAME="RG30101ST-2">2</A>

Current address: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

<A NAME="RG30101ST-3A">3a</A> Ayres DC. Loike JD. Lignans: Chemical, Biological and Clinical Properties   Cambridge University Press; Cambridge: 1990. 

<A NAME="RG30101ST-3B">3b</A> Ward RS. Nat. Prod. Rep.  1999,  16:  75 

Recent reviews:

<A NAME="RG30101ST-4A">4a</A> Charlton JL. J. Nat. Prod.  1998,  61:  1447 

<A NAME="RG30101ST-4B">4b</A> Eich E. ACS Symp. Ser.  1998,  691:  83 

<A NAME="RG30101ST-4C">4c</A> Vlietinck AJ. De Bruyne T. Apers S. Pieters LA. Planta Med.  1998,  64:  97 

Recent reviews:

<A NAME="RG30101ST-5A">5a</A> Rickard SE. Thompson LU. ACS Symp. Ser.  1997,  662:  273 

<A NAME="RG30101ST-5B">5b</A> Tham DM. Gardner CD. Haskell WL. J. Clin. Endocrinol. Metab.  1998,  83:  2223 

<A NAME="RG30101ST-5C">5c</A> Humfrey CDN. Nat. Toxins  1998,  6:  51 

<A NAME="RG30101ST-5D">5d</A> Cline JM. Hughes CL. Cancer Treat. Res.  1998,  94:  107 

<A NAME="RG30101ST-5E">5e</A> Mazur W. Adlercreutz H. Pure Appl. Chem.  1998,  70:  1759 

<A NAME="RG30101ST-5F">5f</A> Bingham S. Pure Appl. Chem.  1998,  70:  1777 

<A NAME="RG30101ST-6A">6a</A> Stitch SR. Toumba JK. Groen MB. Funke CW. Leemhuis J. Vink J. Woods GF. Nature  1980,  287:  738 

<A NAME="RG30101ST-6B">6b</A> Setchell KDR. Lawson AM. Mitchell FL. Adlercreutz H. Kirk DN. Axelson M. Nature  1980,  287:  740 

<A NAME="RG30101ST-6C">6c</A> Axelson M. Sjövall J. Gustafsson BE. Setchell KDR. Nature  1982,  298:  659 

<A NAME="RG30101ST-6D">6d</A> Thompson LU. Robb P. Serraino M. Cheung F. Nutr. Cancer  1991,  16:  43 

<A NAME="RG30101ST-7">7</A> Kamlage S. Sefkow M. Peter MG. Pool-Zobel BL. Chem. Commun.  2001,  331 

<A NAME="RG30101ST-8">8</A> Ohta T. Miyake T. Seido N. Kumobayashi H. Akutagawa S. Takaya H. Tetrahedron Lett.  1992,  33:  635 

<A NAME="RG30101ST-9A">9a</A> Lightfoot A. Schnider P. Pfaltz A. Angew. Chem.  1998,  110:  3047 

<A NAME="RG30101ST-9B">9b</A> Blackmond DG. Lightfoot A. Pfaltz A. Rosner T. Schnider P. Zimmermann N. Chirality  2000,  12:  442 

<A NAME="RG30101ST-10">10</A> Noyori R. Asymmetric Catalysis in Organic Synthesis   Wiley; New York: 1994. 

<A NAME="RG30101ST-11">11</A> Similar observations with R-(+)-BINAP-Ru(II) and other butenolides have been reported: Otha T. Miyake T. Seido N. Kumobayashi H. Takaya H. J. Org. Chem.  1995,  60:  357 

<A NAME="RG30101ST-12A">12a</A> Takabe K. Tanaka M. Sugimoto M. Yamada H. Tetrahedron: Asymmetry  1992,  3:  1385 

<A NAME="RG30101ST-12B">12b</A> Takabe K. Hiyoshi H. Sawada H. Tanaka M. Miyazaki A. Yamada T. Katagiri T. Yoda H. Tetrahedron: Asymmetry  1992,  3:  1399 

<A NAME="RG30101ST-13">13</A> Seebach D. Roggo S. Maetzke T. Braunschweiger H. Cercus J. Krieger M. Helv. Chim. Acta  1987,  70:  1605 

<A NAME="RG30101ST-14">14</A> Kamlage S. Sefkow M. Peter MG. J. Org. Chem.  1999,  64:  2938 

<A NAME="RG30101ST-15">15</A>

Representative Experimental Procedure for 2-Benzyl-butan-1,4-diol (5a):
Diol 6a (1.035 g, 5.81 mmol) was dissolved in dry dichloromethane (44 mL). [Ir(COD)(PHOX)]BARF C (273 mg, 3 mol%), was added. The mixture was hydrogenated with 100 bar H₂ for 3 h using an autoclave. The solvent was removed and the reaction product purified by flash chromatography (silica gel, EtOAc-light petroleum ether, 2:1). Diol 5a was obtained in 0.95 g (92%) as pale yellow oil (ee: 82%). ¹H NMR: δ = 1.58-1.69 m (2 H, H-3), 1.95-2.04 m (1 H, H-2), 2.53 dd (1 H, J = 7.3 and 13.6, H-2"), 2.63 dd (1 H, J = 7.5 and 13.6, H-2"), 3.34 (br s, 2 H, 2 × OH), 3.42-3.76 m (4 H, H-1 and H-4), 7.15-7.30 m (5 H, arom.). ¹³C NMR: δ = 35.2, 38.1, 41.2, 60.9, 65.5, 126.0, 128.3, 129.0, 140.2. IR: 3344, 1042 cm^-1.

<A NAME="RG30101ST-16">16</A> Crabtree RH. Acc. Chem. Res.  1979,  12:  331 

<A NAME="RG30101ST-17">17</A> Shao L. Shiro M. Hitoshi M. Kawano H. Ishii Y. Saburi M. Uchida Y. J. Chem. Soc., Perkin Trans. 1  1990,  1441 ; the authors determined that all β-benzyl substituted diols of a given absolute configuration have the same sign in optical rotation and this allows us to assign the absolute configuration of 5a and 5g by comparison of their signs of optical rotation with that of 5e

<A NAME="RG30101ST-18">18</A> Ley SV. Norman J. Griffith WP. Marsden SP. Synthesis  1994,  639 

<A NAME="RG30101ST-19">19</A> Chênevert R. Mohammadi-Zirani G. Caron D. Dasser M. Can. J. Chem.  1999,  77:  223