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Synlett 2011(8): 1149-1150  
DOI: 10.1055/s-0030-1259943
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Biomimetic Synthesis of (+)-Neroplofurol

Xing Huo*a, Xinfu Pana, Guosheng Huanga, Xuegong Shea
Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
Fax: +86(931)8912582; e-Mail: huox@lzu.edu.cn;
Further Information

Publication History

Received 31 December 2010
Publication Date:
07 April 2011 (online)

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Abstract

(+)-Neroplofurol was biomimetically synthesized in only two steps from natural (+)-nerolidol via Sharpless dihydroxylation and a cascade Shi epoxidation/epoxide ring-opening reaction. All carbons are derived from natural (+)-nerolidol and no protecting groups were utilized, making the synthesis atom-economical and highly efficient. The synthetic neroplofurol was proved to be the enantiomer of the natural one, according to ¹H NMR, ¹³C NMR spectra and optical rotation value. The absolute configuration of natural neroplofurol was also deduced to be 3R,6S,7R,10S.

Key words

Sharpless dihydroxylation - Shi epoxidation - cascade reaction - atom economic - biomimetic synthesis

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(-)-Nerolidol was purchased from Sanming Meilie Perfumery Factory, Fuzhou City, Fujian Province; [α]D 25 +12.

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Spectral data of the target compound: (+)-neroplofurol (1): [α]²5 D +20 (c = 0.1, MeOH). ¹H NMR (400 MHz, CDCl3):
δ = 1.11 (s, 3 H), 1.13 (s, 3 H), 1.25 (s, 3 H), 1.27 (s, 3 H), 1.35 (m, 1 H), 1.48 (m, 1 H), 1.53 (dddd, J = 14.0, 7.2, 7.2, 2.0 Hz, 1 H), 1.66 (ddd, J = 14.4, 7.2, 7.2 Hz, 1 H), 1.78 (ddd, J = 14,2, 7.0, 6.9 Hz, 1 H), 1.90 (m, 2 H), 2.10 (ddd, J = 2.4, 6.0, 12.5 Hz, 1 H), 3.54 (dd, J = 10.8, 2.0 Hz, 1 H), 3.79 (dd, J = 7.6, 7.2 Hz, 1 H), 5.04 (dd, J = 10.8, 1.2 Hz, 1 H), 5.21 (dd, J = 17.6, 1.6 Hz, 1 H), 5.84 (dd, J = 17.6, 10.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 23.86, 25.56, 26.37, 26.95, 27.61, 28.85, 31.32, 39.34, 72.08, 72.91, 77.86, 84.41, 86.46, 112.04, 145.02. IR (solid): 3375, 2971, 1374, 1082 cm-¹. HRMS (ESI): m/z [M + Na]+ calcd for C15H28O4Na: 295.1885; found: 295.1884.

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Representative Experimental Procedure: A solution of AD-mix-β (1.4 g), in t-BuOH-H2O (5:5, 10 mL) was cooled at 0 ˚C. Stirring the mixture at r.t. produced two clear phases; then the methanesulfonamide (95 mg) was added. After stirring for 5 min at 0 ˚C, the olefin 3 (232 mg, 1 mmol) was added in one portion. The reaction mixture was stirred at 0 ˚C for 24 h and then quenched with solid sodium sulfite (1.5 g). The stirring was continued for 45 min, and the solution was extracted with EtOAc (3 × 20 mL). The combined organic phases were washed (2 N KOH), treated with brine, dried (MgSO4), and concentrated. After a short silica gel chromatography, the crude product was then dissolved in MeCN-dimethoxymethane mixture (30 mL, 1:2). A buffer solution (0.5 M solution of Na2B4O7˙10H2O in 4 × 10-4 aq Na2EDTA, 20 mL), Bu4NHSO4 (20 mg) and Shi’s catalyst 6 (180 mg) were added subsequently to the solution. The mixture was cooled to 0 ˚C. A solution of Oxone (560 mg) in aq Na2 (EDTA) (4 × 10-4 M, 13 mL) and K2CO3 (13 mmol) in H2O (13 mL) were added separately over a period of 1 h (using syringe pumps) dropwise to the mixture. After the additions were done, the mixture was stirred for an addi-
tional 30 min at 0 ˚C, diluted with H2O, and extracted with EtOAc (3 × 60 mL). The combined organic layer was washed with brine, and dried over Na2SO4. The product was purified by flash chromatography on silica gel; yield: 176 mg, 0.6 mmol, 60%.