The Journal of Organic Chemistry
NOTE
(m, 2H), 3.93 (s, 3H), 3.32 (s, 3H), 3.15 (t, J = 5.7 Hz, 2H); 13C NMR (101
MHz, CDCl3) δ 163.8, 160.7, 159.9, 144.9, 142.9, 138.5, 136.5, 128.2, 126.7,
126.2, 124.5, 120.9, 120.3, 99.8, 98.4, 66.7, 55.7, 55.6, 30.2; HRMS (ESI) m/z
calcd for C21H18O4Na (M þ Na)þ 357.1103, found 357.1111; IR (thin film)
3095, 2910, 1715, 1595 cmꢀ1; mp 185ꢀ186 °C.
by the National Institutes of Health (R56AI80931-01 and
R01AI080931-01). M.G.L. thanks the Fundaciꢀon Ramon Areces
for a postdoctoral fellowship and A.J.B. acknowledges support in
the form of a Bradford Borge Graduate Research Fellowship
from UC Davis.
9: Double Labeling Experiment. An equimolar amount of 7
(0.030 g, 0.079 mmol) and 8 (0.019 g, 0.079 mmol) was dissolved in
0.5 mL of THF and the solution was cooled to ꢀ78 °C. To this solution
was added a 1.5 M solution of n-BuMgCl in THF (0.052 mL, 0.079
mmol). The reaction was stirred for 10 min and was then quenched with
saturated ammonium chloride (5 mL). The resulting layers were
separated, and the aqueous layer was extracted with 2 ꢁ 10 mL of
EtOAc. The combined organic layers were washed with 10 mL of brine,
dried (MgSO4), and concentrated in vacuo to afford a crude oil. GCMS and
NMR analysis showed only methoxy displacement and no observable
evidence of tosylate displacement. The crude product was purified by flash
chromatography (20:80 EtOAc/hexanes) to afford 9 (0.020 g, 95%) as a
colorless oil. 1H NMR (300 MHz, CDCl3) δ8.14ꢀ8.09(m, 1H), 7.80ꢀ7.43
(m, 5H), 4.25 (t, J = 6.7 Hz, 2H), 3.36ꢀ3.2 (m, 2H), 1.81ꢀ1.60 (m, 2H),
1.53ꢀ1.40 (m, 4H), 0.99 (t, J = 7.4 Hz, 3H), 0.92 (t, J = 7.3 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 169.1, 141.985, 135.2, 132.3, 128.9, 128.1, 127.3,
126.7, 126.4, 126.2, 125.5, 67.0 33.9, 29.6, 23.6, 22.4, 14.2, 10.9; HRMS (ESI)
m/z calcd for C18H23O2 (M þ H)þ 271.1693, found 271.1690; IR (thin
’ REFERENCES
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been reviewed extensively. For recent summaries of work on the Suzuki
(RB(OR)2), Negishi (RZnX), Kumada (RMgX), and Stille (RSnBu3)
reactions, see: K€urti, L.; Czakꢀo, B. Strategic Applications of Named
Reactions in Organic Synthesis; Elsevier Academic Press: Burlington,
MA, 2005. Li, J. J.; Corey, E. J. Name Reactions for Homologations; John
Wiley and Sons: Hoboken, JJ, 2009.
(2) Fuson, R. C.; Speck, S. B. J. Am. Chem. Soc. 1942, 64, 2446–2448.
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film) 3070, 2937, 2880, 1715, 1595 cmꢀ1
.
Competition Experiment. An equimolar amount of 5a (0.10 g,
0.462 mmol) and 11 (0.10 g, 0.462 mmol) was dissolved in 2 mL of THF
and the solution was cooled to ꢀ78 °C. To this solution was added a
2.0 M solution of i-PrMgCl in THF (0.23 mL, 0.462 mmol). The reaction
was stirred for 10 min and was then quenched with saturated ammonium
chloride (5 mL). The resulting layers were separated, and the aqueous layer
was extracted with 2 ꢁ 10 mL of EtOAc. The combined organic layers were
washed with 10 mL of brine, dried (MgSO4), and concentrated in vacuo to
afford a crude oil. NMR analysis showed only displacement at the
1-position. The crude product was purified by flash chromatography
(20:80 EtOAc/hexanes) to afford 6d (0.079 g, 75%) as the only product.
20e: According to general procedure 1, 18c (0.035 g, 0.1457 mmol)
was reacted with a solution of i-PrMgCl in THF (2.0 M, 0.073 mL) to
afford a crude oil. The oil was purified by flash chromatography (10:90
EtOAc/hexanes) to yield the product 20e as a colorless oil (0.033 g,
90%). 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.0 Hz, 1H), 7.77 (d,
J = 8.3 Hz, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.53ꢀ7.34 (m, 2H), 7.16 (d, J =
8.5 Hz, 1H), 3.60ꢀ3.42 (m, 1H), 2.81 (t, J = 7.4 Hz, 2H), 1.71ꢀ1.59 (m,
2H), 1.50 (d, J = 7.2 Hz, 6H), 1.35 (dd, J = 7.4, 14.8 Hz, 2H), 0.88 (t, J =
7.3 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 210.0, 140.9, 139.3, 134.9,
131.8, 129.4, 127.1, 126.4, 126.3, 126.1, 123.0, 44.4, 31.6, 26.5, 22.9, 22.6,
14.2; HRMS (ESI) m/z calcd for C18H23O (M þ H)þ 255.1743, found
(10) See, for example: (a) Meyers, A. I.; Flisak, J. R.; Aitken, R. A.
J. Am. Chem. Soc. 1987, 109, 5446–5452. (b) Patten, A. D.; Nguyen
Nhan, H.; Danishefsky, S. J. J. Org. Chem. 1988, 53, 1003–1007.
(c) Rizzacasa, M. A.; Sargent, M. V. Chem. Commun. 1990, 894–896.
(d) Meyers, A. I.; Willemsen, J. J. Tetrahedron 1998, 54, 10493–10511.
255.1742; IR (thin film) 3095, 2959, 2865, 1687 cmꢀ1
.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures, spec-
b
tra (1H NMR, 13C NMR, NMR) for all new compounds, and a
CIF file for 4b. This material is available free of charge via the
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: shaw@chem.ucdavis.edu.
’ ACKNOWLEDGMENT
This research was supported by the Petroleum Research
Fund (administered by the American Chemical Society) and
3518
dx.doi.org/10.1021/jo102537n |J. Org. Chem. 2011, 76, 3515–3518