Journal of the American Chemical Society
ARTICLE
afforded 45 mg (>99%, 91% ee) of the desired product as a white solid.
Rf = 0.25 (20% EtOAc in petroleum ether, KMnO4 stain). Mp: 49ꢀ
51 °C. [α]D25 = ꢀ34.2° (91% ee, c 9.3 mg/mL, CHCl3). 1H NMR (400
MHz, CDCl3): δ 7.32ꢀ7.28 (m, 5H), 5.78 (dddd, J = 17.0, 10.3, 8.2, 6.5
Hz, 1H), 5.13 (m, 1H), 4.77 (d, J = 8.0 Hz, 1H), 4.10 (dq, J = 10.8, 7.2
Hz, 1H), 3.99 (dq, J = 10.8, 7.2 Hz, 1H), 3.36 (s, 1H), 3.06 (d, J = 8.0 Hz,
1H), 2.86 (ddt, J = 14.0, 6.9, 1.2, 0.6 Hz, 1H), 2.63 (ddd, J = 14.0, 7.4, 0.6
Hz, 1H), 1.17 (t, J = 7.2 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ
173.6, 139.4, 132.5, 128.5, 128.3, 127.4, 119.4, 80.7, 77.7, 62.3, 40.7, 14.3
ppm. IR (neat): νmax 3649, 3503, 1733, 1717, 1699, 1558, 1541, 1507,
1456 1223, 1150 cmꢀ1. HPLC: Tr = 13.1 (minor) and 14.6 (major)
(Chiracel AD Chiral HPLC, λ 220 nm, heptane:iPrOH = 90:10,
1.0 mL/min). HRMS (ES+) m/z calcd for C14H18NaO4 [M + Na]+
273.1103, found 273.1100.
7.0 Hz, 3H) ppm. 13C NMR (125 MHz, CDCl3): δ 174.5, 139.1,
128.2, 128.0, 127.0, 77.9, 775, 62.0, 22.6, 13.9 ppm. IR (neat): νmax
3473, 2984, 2939, 1730, 1453, 1243, 1160, 1049, 1026, 702 cmꢀ1
.
HPLC: Tr = 16.5 (minor) and 18.0 (major) (Chiracel AD Chiral
HPLC, l = 220 nm, heptane:iPrOH = 90:10, 0.8 mL/min).
’ ASSOCIATED CONTENT
S
Supporting Information. Text and figures giving ex-
b
perimental procedures and spectral data for all new com-
pounds (1H NMR, 13C NMR, IR, HRMS) and tables and a
CIF files giving crystal data for 38. This material is available free of
4.3.2. (S)-Ethyl 2-Hydroxy-2-((S)-hydroxy(phenyl)methyl)-3,3-di-
methylpent-4-enoate (23). To a solution of (S)-ethyl 2-diazo-3-hydroxy-
3-phenylpropanoate (40 mg, 0.18 mmol, 1.0 equiv) in acetone (2 mL)
was added DMDO (∼0.1 M solution in acetone, 6 mL, 0.6 mmol, 3.3
equiv) at ꢀ35 °C. Upon completion of the reaction (checked by TLC,
approximately 1 h) the reaction mixture was warmed to room tempera-
ture and concentrated. CH2Cl2 was added, and the solution was dried
over Na2SO4 and concentrated. The residue was dissolved in DMF
(1.6 mL), and indium powder (23 mg, 0.2 mmol, 1.1 equiv) and 3,3-
dimethylallyl bromide (90% pure, 46.6 μL, 0.36 mmol, 2.0 equiv)
were added. After 16 h additional 3,3-dimethylallyl bromide (90%
pure, 53.4 μL, 0.44 mmol, 2.0 equiv) was added and the reaction
mixture stirred for 2 h at 35 °C. The reaction was quenched with
saturated aqueous NaHCO3 solution. After extraction with Et2O
(4 ꢁ 10 mL) the organic layers were combined, washed with H2O
(50 mL), dried over Na2SO4, and concentrated. The crude product
was purified by silica gel chromatography (gradient 20ꢀ33% EtOAc
in petroleum ether) and afforded the title compound (20.7 mg, 62%,
95% ee) as a white solid. Rf = 0.40 (20% EtOAc in petroleum ether).
Mp: 97ꢀ99 °C. [α]D25 = +24.0° (95% ee, c 3.3 mg/mL, CHCl3). 1H
NMR (500 MHz, CDCl3): δ 7.31ꢀ7.24 (m, 5H), 6.29 (dd, J = 17.6,
10.8 Hz, 1H), 5.19ꢀ5.09 (m, 3H), 4.00 (dq, J = 10.8, 7.2 Hz, 1H),
3.81 (dq, J = 10.8, 7.2 Hz, 1H), 3.55 (s, 1H), 2.90 (d, J = 8.2 Hz, 1H),
1.31 (s, 3H), 1.27 (s, 3H), 1.16 (t, J = 7.2 Hz, 3H). 13C NMR (125
MHz, CDCl3): δ 173.6, 144.7, 140.2, 128.1, 127.9, 127.6, 113.1, 83.1,
74.9, 62.0, 43.7, 23.5, 23.2, 13.8 ppm. IR (neat): νmax 3465, 2979,
1715, 1261, 1105 cmꢀ1. HPLC: Tr = 7.3 (minor) and 9.1 (major)
(Chiracel IA Chiral HPLC, l = 220 nm, heptane:iPrOH = 90:10,
1.0 mL/min). ee = 95%. HRMS (ES+): m/z calcd for C16H22NaO4
[M + Na]+ 301.1416, found 301.1408.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: bmtrost@stanford.edu.
’ ACKNOWLEDGMENT
This work has been supported by the National Institutes of
Health (No. GM33049) and the National Science Foundation.
S.M. acknowledges Stanford University for a graduate fellowship.
P.K. acknowledges Landesstiftung BW for the Baden-W€urttemberg-
Stipendium undergraduate scholarship. P.E. acknowledges the
DAAD and the Bayer Fellowship Program.
’ REFERENCES
(1) Selected examples: (a) Forbes, J. E.; Pattenden, G. J. Chem. Soc.,
Perkin. Trans. 1 1991, 1959. (b) Clive, D. L. J.; Minaruzzaman Org. Lett.
2007, 9, 5315. (c) Xie, W.; Ding, D.; Zi, W.; Li, G.; Ma, D. Angew. Chem.,
Int. Ed. 2008, 47, 2844. (d) Boger, D. L.; Ichikawa, S.; Zhong, W. J. Am.
Chem. Soc. 2001, 123, 4161. (e) Trost, B. M.; Friedreksen, M. U.;
Papillon, J. P.; Harrington, P. E.; Shin, S.; Shireman, B. T. J. Am. Chem.
Soc. 2005, 127, 3666. (f) Maki, K.; Motoki, R.; Fujii, K.; Kanai, M.;
Kobayashi, T.; Tamura, S.; Shibasaki, M. J. Am. Chem. Soc. 2005,
127, 17111. (g) Trost, B. M.; Probst, G. D.; Schoop, S. J. Am. Chem.
Soc. 1998, 120, 9228.
(2) Selected examples: (a) Hatkeyama, S.; Matsui, Y.; Suzuki, M.;
Sakurai, K.; Takano, S. Tetrahedron Lett. 1985, 26, 6485. (b) Shao, H.;
Rueter, J. K.; Goodman, M. J. Org. Chem. 1998, 63, 5240. (c) Claudel, S.;
Olszewski, T. K.; Mutzenardt, P.; Aroulanda, C.; Coutrot, P.; Grison, C.
Tetrahedron 2006, 62, 1787.
4.3.3. Zinc Based Method: (2S,3S)-Ethyl 2,3-Dihydroxy-2-methyl-3-
phenylpropanoate (27). To a solution of (S)-ethyl 2-diazo-3-hydroxy-
3-phenylpropanoate (50 mg, 0.22 mmol, 1.0 equiv) in acetone (2 mL)
was added DMDO (∼0.1 M solution in acetone, 6 mL, 0.6 mmol, 2.7
equiv) at ꢀ35 °C. Upon completion of the reaction (checked by TLC,
approximately 1 h) the reaction mixture was warmed to room tempera-
ture and concentrated. CH2Cl2 was added and the solution dried over
Na2SO4 and concentrated. The residue was dissolved in THF (1 mL)
and cooled to ꢀ78 °C. Dimethylzinc (1.2 M solution in toluene, 0.6 mL,
0.66 mmol, 3.0 equiv) was added dropwise, and the reaction mixture was
warmed gently to room temperature. After 40 h the reaction mixture was
quenched with pH 7 buffer and extracted with diethyl ether (4 ꢁ
10 mL). The organic layers were combined, dried over Na2SO4, and con-
centrated. The crude product was purified by silica gel chromatography
using a gradient of 15ꢀ33% EtOAc in petroleum ether to afford 35 mg
(71%, 94% ee) of the desired product as a light yellow oil. Rf = 0.15 (20%
(3) Recent examples: (a) Lim, S. M.; Hill, N.; Myers, A. G. J. Am.
Chem. Soc. 2009, 131, 5763. (b) Kim, H. C.; Kang, S. H. Angew. Chem.,
Int. Ed. 2009, 48, 1827.
(4) (a) Robles, O.; McDonald, F. Org. Lett. 2009, 11, 5498.
(b) Trost, B. M.; Probst, G.; Schoop, A. J. Am. Chem. Soc. 1998,
120, 9228.
(5) (a) Misaki, T.; Takimoto, G.; Sugimura, T. J. Am. Chem. Soc.
2010, 132, 6286. (b) Luo, J.; Wang, H.; Han, X.; Xu, L.-W.; Kwiatkowski,
J.; Huang, K.-W.; Lu, Y. Angew. Chem., Int. Ed. 2011, 50, 1861. (c) Liu,
C.; Dou, X.; Lu, Y. Org. Lett. 2011, 13, 5248. For a recent review:
(d) Trost, B. M.; Brindle, C. S. Chem. Soc. Rev. 2010, 39, 1600.
(6) Trost, B. M.; Malhotra, S.; Fried, B. A. J. Am. Chem. Soc. 2009,
131, 1674.
(7) For the addition of hydride nucleophiles to β-hydroxy α-keto
esters see: (a) Liao, M.; Yao, W.; Wang, J. Synthesis 2004, 16, 2633. (b)
Yao, W.; Wang, J. Org. Lett. 2003, 5, 1527. For precedence for α-ketol
rearrangement: (c) Zhu, Y.; Tu, Y.; Yu, H.; Shi, Y. Tetrahedron Lett.
1998, 39, 7819. (d) Paquette, L. A.; Lobben, P. C. J. Org. Chem. 1998,
63, 5604. (e) Steward, K. M.; Johnson, J. S. Org. Lett. 2010, 12, 2864.
(8) Recent methods for the asymmetric synthesis of 1,2-diols bearing
a tertiary carbinol: (a) Giampietro, N. C.; Kampf, J. W.; Wolfe, J. P. J. Am.
25
EtOAc in petroleum ether). [α]D = +10.0° (94% ee, c 10.0 mg/mL,
CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.36ꢀ7.27 (m, 5H), 4.74 (d, J =
7.4Hz, 1H), 4.11 (dq, J=10.4, 7.0 Hz, 1H), 4.03 (dq, J= 10.4, 7.0 Hz, 1H),
3.34 (s, 1H), 3.01 (d, J = 7.4 Hz, 1H), 1.56 (s, 3H), 1.18 (dd, J = 7.0,
2083
dx.doi.org/10.1021/ja206995s |J. Am. Chem. Soc. 2012, 134, 2075–2084