A Facile Solid-Phase Synthesis of Substituted 2(5H)-Furanones with Sulfone Traceless Linker

Abstract

A novel solid-phase synthetic method for substituted 2(5H)-furanones with traceless sulfone linker strategy has been developed. The products were obtained in good yields and excellent purities.

solid-phase organic synthesis - traceless sulfone linker - substituted 2(5H)-furanone

References

Recent reviews on SPOS:

<A NAME="RU24004ST-1A">1a</A> Guillier F. Orain D. Bradley M. Chem. Rev.  2000,  100:  2091 

<A NAME="RU24004ST-1B">1b</A> Sammelson RE. Kurth MJ. Chem. Rev.  2001,  101:  137 

<A NAME="RU24004ST-1C">1c</A> Czarnik AW. Solid-Phase Organic Synthesis   Vol. 1:  Wiley; New York: 2001. 

<A NAME="RU24004ST-1D">1d</A> Nicolaou KC. Hanko R. Hartwig H. Handbook of Combinatorial Chemistry   Wiley-VCH; Weinheim: Germany: 2002. 

<A NAME="RU24004ST-1E">1e</A> Dolle RE. J. Comb. Chem.  2002,  4:  369 

<A NAME="RU24004ST-2A">2a</A> Brima TS. inventors; U.S. Patent  4,968,817.  ; Chem. Abstr. 1991, 114, 185246y

<A NAME="RU24004ST-2B">2b</A> Tanabe A. inventors; Jpn. Kokai Tokyo Koho, JP  88,211,276.  ; Chem. Abstr. 1989, 110, 94978q

<A NAME="RU24004ST-2C">2c</A> Lee GCM. inventors; Eur. Patent EP  372,940.  ; Chem. Abstr. 1990, 113, 191137j

<A NAME="RU24004ST-2D">2d</A> Ducharme Y, Gauthier JY, Prasit P, Leblanc Y, Wang Z, Leger S, and Therien M. inventors; PCT Int. Appl. WO  95,00501.  ; Chem. Abstr. 1996, 124, 55954y

<A NAME="RU24004ST-2E">2e</A> Lee Gary CM, and Garst ME. inventors; PCT Int. Appl. WO  91 16,055.  ; Chem. Abstr. 1992, 116, 59197m

<A NAME="RU24004ST-3A">3a</A> Fujita K. Watanabe K. Oishi A. Ikeda Y. Taguchi Y. Synlett  1999,  1760 

<A NAME="RU24004ST-3B">3b</A> Fujita K. Taka H. Oishi A. Ikeda Y. Taguchi Y. Fujie K. Saeki T. Sakuma M. Synlett  2000,  1509 

<A NAME="RU24004ST-3C">3c</A> Ma S. Duan D. Shi Z. Org. Lett.  2000,  2:  1419 

<A NAME="RU24004ST-3D">3d</A> Ma S. Duan D. Wang Y. J. Comb. Chem.  2002,  4:  239 

<A NAME="RU24004ST-3E">3e</A> Fujita K. Hashimoto S. Oishi A. Taguchi Y. Tetrahedron Lett.  2003,  44:  3793 

<A NAME="RU24004ST-3F">3f</A> Huang X. Sheng S.-R. J. Comb. Chem.  2003,  5:  273 

<A NAME="RU24004ST-4A">4a</A> Chen Y. Lam YL. Lai YH. Org. Lett.  2003,  5:  1067 

<A NAME="RU24004ST-4B">4b</A> Chen Y. Lam YL. Lai YH. Org. Lett.  2002,  4:  3935 

<A NAME="RU24004ST-4C">4c</A> Cheng WC. Kurth MJ. J. Org. Chem.  2002,  67:  4387 

<A NAME="RU24004ST-4D">4d</A> Cheng WC. Wong M. Olmstead MM. Kurth MJ. Org. Lett.  2002,  4:  741 

<A NAME="RU24004ST-4E">4e</A> Cheng WC. Lin CC. Kurth MJ. Tetrahedron Lett.  2002,  43:  2967 

<A NAME="RU24004ST-4F">4f</A> Cheng WC. Wong M. Olmstead MM. Kurth M. J. Org. Chem.  2001,  66:  5528 

<A NAME="RU24004ST-4G">4g</A> Huang W. Cheng S. Sun W. Tetrahedron Lett.  2001,  42:  1973 

<A NAME="RU24004ST-4H">4h</A> Cheng WC. Halm C. Evarts JB. Olmstead MM. Kurth MJ. J. Org. Chem.  1999,  64:  8557 

<A NAME="RU24004ST-4I">4i</A> Kulkarni BA. Ganesan A. Tetrahedron Lett.  1999,  40:  5633 

<A NAME="RU24004ST-4J">4j</A> Yamada M. Miyajima T. Horikawa H. Tetrahedron Lett.  1998,  39:  289 

<A NAME="RU24004ST-4K">4k</A> Halm C. Evarts J. Kurth MJ. Tetrahedron Lett.  1997,  38:  7709 

<A NAME="RU24004ST-4L">4l</A> Farrall MJ. Frechet JM. J. Org. Chem.  1976,  41:  3877 

<A NAME="RU24004ST-4M">4m</A> Fyles TM. Leznoff CC. Can. J. Chem.  1976,  54:  935 

<A NAME="RU24004ST-4N">4n</A> Fyles TM. Leznoff CC. Can. J. Chem.  1978,  56:  1031 

<A NAME="RU24004ST-4O">4o</A> Chen Y. Lam YL. Lee SY. Chem. Lett.  2001,  274 

<A NAME="RU24004ST-5">5</A>

Preparation of Polymer-Supported Phenylmethylsulfone 2: Polystyrene/1% divinylbenzene lithium sulfinate (1, 1.0 g, 1.0 mmol), prepared according to literature, [4h] was swollen under nitrogen in THF-DMF (2:1, 10 mL). MeI (5.0 mmol) was added and the reaction mixture was shaken at 80 °C for 15 h. After which, the reaction mixture was cooled to r.t., quenched with H₂O, and filtered. The resin was washed successively with THF-H₂O (2:1, 3 × 10 mL), THF (2 × 5 mL), CH₂Cl₂ (2 × 5 mL) and Et₂O (2 × 5 mL), and then dried under vacuum overnight to afford the pale yellow resin 2. FT-IR (single bead reflection): 1600, 1495, 1452, 1380, 1313, 1150 cm^-1.

<A NAME="RU24004ST-6">6</A> Oxley P. Partridge MW. Robson TD. Short WF. J. Chem. Soc.  1946,  763 

<A NAME="RU24004ST-7">7</A>

General Procedure for the Solid-Phase Synthesis of Target Molecules ( 6): Under nitrogen n-BuLi (2.0 mmol, 1.65 M, 1.2 mL) was added to DMSO (4.0 mmol) in THF (10 mL) at 0 °C and stirred for 5 min. The resulting dimsyl anion solution was transferred to a suspension of polymer 2 (1.0 g, 1.0 mmol) in THF (8 mL) at r.t. After stirring for 30 min, epoxide (3.0 mmol) was added to this mixture and stirred for 2 h, the color of the breads turned light orange. The reaction was quenched with 10% HCl (aq) after 1 h and the resin was filtered, washed and dried to afford resin 3 as pale yellow beads. A solution of methyl chloroformate (2.0 mmol) in THF (2 mL) was added to a suspension of the obtained resin 3 in THF (8 mL) at 0 °C, and followed with pyridine (1.5 mmol, 0.2 mL). The mixture was stirred 0 °C for 1 h and the γ-phenylsulfonylalkyl methyl carbonate resin 4 was collected by filtration and washed successively with 3% HCl (3 × 10 mL), H₂O (3 × 10 mL), THF (3 × 5 mL), and dried in a vacuum. Subsequently, the resin 4 was swollen in THF (10 mL) and treated with LDA (2.0 mmol) at -78 °C for 1 h under dry nitrogen, at 0 °C for 2 h, and then at r.t. for 1 h. The resin 5 was collected by filtration and washed successively with THF-H₂O (1:1, 30 mL), H₂O (3 × 10 mL), and THF (3 × 5 mL). After drying in a vacuum, the resin 5 was swollen in CH₂Cl₂ (10 mL) and treated with Et₃N (5.0 mmol) at r.t. for 10 h. The residual resin was collected by filtration and washed with CH₂Cl₂ (2 × 3 mL). The organic extracts were washed with H₂O, dried over anhyd MgSO₄ and concentrated to afford crude product 6 with 90-95% purity (determined by HPLC), which was further purified by silica gel chromatographic column (petroleum ether-EtOAc = 20:1) affording the pure products for ¹H NMR and MS analysis.