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Thalen et al.
JOCArticle
TABLE 4. Oxidation of Olefins (R)-5 and (S)-5a
aConditions: [A] III, 2 mol % of RuCl3, 4.1 equiv of NaIO4; [B] III, 0.5 equiv of KMnO4, 5 equiv of NaIO4, 1 equiv of K2CO3; [C] III, 5 mol % of OsO4,
4 equiv of oxone. bIsolated yield. cDetermined by GC.
13C NMR spectral data were in accordance with literature
data.25
tR(S) = 27.23 min). NMR spectral data were in accordance with
published data.26 1H NMR (400 MHz, CDCl3): δ 7.43-7.38
(m, 2H), 7.37-7.31 (m, 2H), 7.29-7.24 (m, 1H), 6.62 (d, J =
15.9 Hz, 1H), 6.22 (d, J = 15.9, 6.8 Hz, 1H), 5.57 (d, J = 6.8, 6.5
Hz, 1H), 2.33 (t, J = 7.3 Hz, 2H), 1.7 (tq, J = 7.3, 7.4 Hz, 2H), 1.43
(d, J = 6.5 Hz, 3H), 0.98 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 173.0, 136.5, 131.5, 129.1, 128.7, 128.0, 126.7, 70.8, 36.7,
20.5, 18.6, 13.8. [R]27D = -105.8 (c 1.0, CHCl3).
Synthesis of Enantiomerically Pure Esters (S)-3 and (R)-30.
4-Phenyl-3-buten-2-yl Acetate ((R)-30). Prepared via DKR
according to a literature procedure (89% yield and >99% ee).16
General Procedure for the Copper(I)-Catalyzed Allylic Sub-
stitution Reactions. (S)-5a. The allylic acetate (R)-30 (190 mg,
(S)-4-Phenyl-3-buten-2-yl Butanoate ((S)-3). Complex
8
(16 mg, 25 μmol), Subtilisin Carlsberg:Brij:octyl-β-glycopyra-
noside, 4:1:1 (20 mg, prepared as previously reported3), Na2CO3
(106 mg, 1.0 mmol), and t-BuOK (50 μL, 0.5 M in THF) were
stirred in toluene (0.5 mL) for 6 min. Thereafter, a solution of
racemic alcohol 1 (74.1 mg, 0.50 mmol) in THF (2 mL) was
added. After 4 min, trifluoroethylbutyrate (225 μL, 1.5 mmol)
was added, and the mixture was stirred at 40 °C under an argon
atmosphere. After 48 h, the reaction mixture was filtered through
a plug of silica and was washed with ethyl acetate. The crude pro-
duct was concentrated in vacuo, and column chromatography
(pentane/EtOAc, 60:1) afforded (S)-3 (75%, 82.2 mg) as a color-
less oil in 95% ee. The optical purity was determined by HPLC
analysis (OJ column, i-hexane/i-PrOH, 99:1, tR(R) = 24.63,
tR(S) = 27.28 min).
Enantiomeric Excess Enhancement via Hydrolysis of (R)-4-
Phenyl-3-buten-2-yl Butanoate ((S)-3). (S)-3 (95% ee, 109.1 mg,
0.5 mmol) and CALB (10 mg) were then suspended in a 0.5 M
phosphate buffer (2 mL, pH 7.2) and stirred for 2 h at 60 °C. The
mixture was filtered, and the aqueous phase was extracted three
times with EtOAc. The organic phases were combined and
washed once with 2 M NaHCO3. The organic phase was dried
over Na2SO4, and the product was concentrated in vacuo.
Column chromatography (pentane/EtOAc, 60:1) afforded (S)-3
(96%) in >99% ee. The optical purity was determined by HPLC
analysis (OJ column, i-hexane/i-PrOH, 99:1, tR(R) = 24.63,
1.0 mmol) and CuBr SMe2 (20.5 mg, 0.1 mmol) were mixed in
3
THF (9 mL) and cooled to 0 °C. A solution of ((3-fluoro-4-
phenyl)phenyl)MgBr in THF (3.0 mL, 0.5 M) was added, and
the reaction mixture and was stirred at the given temperature.
The reaction mixture was quenched after 5 h by addition of
HCl(aq) (2 M, 10 mL), followed by addition of 2-nonanol (50 μL,
0.26 mmol) as internal standard. The organic solvent was
removed in vacuo, and Et2O (10 mL) was added. The product was
extracted with Et2O (3 ꢀ 10 mL). The combined organic phase
was washed with H2O (1 ꢀ 10 mL) and dried over Na2SO4. The
solvent was removed in vacuo to afford the crude product, which
was purified bycolumn chromatography (pentane/EtOAC, 100:0
to 97:3). (S)-5a was obtained in 92% yield and >99% ee. The
optical purity was determined by HPLC analysis (OJ column,
i-hexane/i-PrOH, 85:15; flow 1.0, tR(S) = 13.6 min, tR(R) = 18.6
min). NMR spectral data were in accordance with published
data.27 [R]27D = -39.2 (c 1.00, (CH3)2CO).
General Procedure for Oxidative C-C Double Bond Cleavage.
(S)-7b. Method [A]. Oxidative cleavage of the olefin (S)-5a was
performed on 1.0 mmol scale according to the Sharpless pro-
cedure13 and as previously described.14 Olefin (S)-5a (302 mg,
1 mmol), RuCl3 H2O (4.2 mg, 0.02 mmol), NaIO4 (877 mg, 4.1
3
mmol), MeCN (2 mL), CCl4 (2 mL), and H2O (3 mL) were
charged in a 25 mL round-bottom flask and stirred under
(25) Onaran, M. B.; Seto, C. T. J. Org. Chem. 2003, 68, 8136–8141.
(26) Kim, M. J.; Han, K. L.; Park, J. Bull. Korean Chem Soc. 2007, 28,
2096–2098.
(27) Rodriguez, D.; Perez Sestelo, J.; Sarandeses, L. A. J. Org. Chem.
2004, 69, 8136–8139.
6846 J. Org. Chem. Vol. 75, No. 20, 2010