1412
A. A. Fuller et al.
LETTER
(14) General Procedure for Preparation of 10a–e, 11a–b:
To a solution of 8 or 9 (0.8 mmol, 1 equiv) in toluene (5 mL)
cooled in a dry ice–acetone bath, BF3·OEt2 (O.31 mL, 2.5
mmol, 3.1 equiv) was added dropwise, and the resulting
solution was stirred for 0.5 h with continued cooling. A
solution of the organolithium reagent (5.8 mmol, 7.2 equiv)
was then added over 15 min. After TLC analysis indicated
complete consumption of starting material (typically 3–5 h),
the reaction was quenched with 15 mL sat. NaHCO3. The
mixture was extracted with Et2O (3 × 20 mL), and the
combined extracts were washed with H2O (3 × 15 mL), brine
(1 × 15 mL), dried over Na2SO4, and concentrated. The
crude mixture was passed through a short plug of silica (9:1
hexanes–EtOAc) and after concentration, the residue was
dissolved in 4 mL THF, cooled in an ice–H2O bath, and
TBAF (4 equiv) was added dropwise. The reaction was
allowed to warm to ambient temperature while monitoring
by TLC. Following the consumption of starting material, the
reaction mixture was diluted with H2O (10 mL) and
extracted with Et2O or EtOAc. Combined extracts were
washed with brine (1 × 10 mL), dried over Na2SO4,
concentrated, and purified by flash chromatography. Only
the major diastereomer was carried on in subsequent steps.
(15) 10a: Mp 73–75 °C; [a]D = –85.0 (c 0.44, CHCl3).
10b: [a]D = –85.0 (c 0.44, CHCl3).
11b: IR (thin film): 3441, 2969, 1494 cm–1. 1H NMR (500
MHz, CDCl3): d = 0.44 (t, 3 H, J = 7.6 Hz), 0.76 (d, 3 H,
J = 6.1 Hz), 0.84–0.93 (m, 1 H), 1.49–1.57 (m, 1 H), 1.96 (s,
1 H), 3.57 (d, 1 H, J = 4.9 Hz), 3.85–3.91 (m, 1 H), 3.73 (dd,
1 H, J = 4.9, 9.0 Hz), 6.14 (br s, 1 H), 7.24–7.35 (m, 4 H),
7.39–7.42 (m, 4 H), 7.66 (d, 2 H, J = 7.3 Hz). 13C NMR (125
MHz, CDCl3): d = 9.35, 18.91, 29.53, 61.01, 68.25, 74.98,
87.95, 126.59, 127.11, 127.62, 128.54, 129.05, 129.73,
136.22, 143.41. HRMS (ESI): m/z calcd for [C19H23NO2 +
H]+: 298.1807; found: 298.1797.
(16) 14a: IR (thin film): 3316, 2956, 1712, 1166 cm–1. 1H NMR
(500 MHz, CD3OD): d = 0.93 (d, 6 H, J = 6.6 Hz), 1.32 (s, 3
H), 1.42 (s, 9 H), 1.52 (dd, 1 H, J = 13.9, 5.1 Hz), 1.69–1.78
(m, 1 H), 1.86 (dd, 1 H, J = 13.5, 6.3 Hz), 2.48 (d, 1 H,
J = 13.9 Hz), 2.80 (d, 1 H, J = 14.2 Hz). 13C NMR (125
MHz, CD3OD): d = 24.67, 25.14, 25.28, 28.85, 31.12, 44.68,
47.42, 54.80, 79.55, 156.57, 174.88. HRMS (ESI): m/z calcd
for [C13H25NO4 + Na]+: 282.1681; found: 282.1684.
14b: mp 136–138 °C. IR (thin film): 3305, 2926, 1712,
1651, 1165 cm–1. 1H NMR (500 MHz, CD3OD): d = 0.65 (s,
3 H), 0.78 (s, 3 H), 1.37 (s, 9 H), 1.51–1.60 (m, 1 H), 1.83–
1.92 (m, 1 H), 2.13 (dd, 1 H, J = 13.8, 5.0 Hz), 3.03 (d, 1 H,
J = 14.2 Hz), 3.21 (d, 1 H, J = 14.2 Hz), 7.19 (t, 1 H, J = 7.2
Hz), 7.27–7.31 (m, 2 H), 7.32–7.36 (m, 2 H). 13C NMR (125
MHz, CDCl3): d = 23.67, 24.43, 27.76, 29.69, 41.58, 49.32,
59.67, 81.46, 125.37, 126.32, 127.77, 144.83, 157.74,
175.28. HRMS (ESI): m/z calcd for [C18H27NO4 + Na]+:
344.1838; found: 344.1848.
10c: [a]D = –97.3 (c 0.70, CHCl3). IR (thin film): 3392,
2956, 2930, 2871, 1469, 1368 cm–1. 1H NMR (500 MHz,
CDCl3): d = 0.78 (d, 3 H, J = 6.6 Hz), 0.82 (d, 3 H, J = 7.0
Hz), 1.21 (d, 3 H, J = 6.6 Hz), 1.43–1.49 (m, 1 H), 1.79–1.81
(m, 2 H), 1.91 (dd, 1 H, J = 12.5, 8.1 Hz), 2.84 (dd, 1 H,
J = 12.8, 7.7 Hz), 3.70–3.77 (m, 1 H), 3.89–3.94 (m, 1 H),
6.32–6.34 (m, 2 H), 7.36–7.37 (m, 1 H). 13C NMR (100
MHz, CDCl3): d = 19.53, 23.66, 23.88, 25.57, 43.59, 46.31,
68.53, 69.73, 85.40, 106.72, 110.52, 141.77, 155.97. HRMS
(ESI): m/z calcd for [C13H21NO3 + Na]+: 262.1419; found:
262.1420.
10d: [a]D = –86.8 (c 0.59, CHCl3). IR (thin film): 3392,
2955, 2926, 2871, 1565, 1453, 1368 cm–1. 1H NMR (500
MHz, CDCl3): d = 0.80 (d, 3 H, J = 6.8 Hz), 0.85 (d, 3 H,
J = 6.6 Hz), 1.21 (d, 3 H, J = 6.3 Hz), 1.49–1.52 (m, 1 H),
1.72–1.87 (m, 3 H), 2.19–2.26 (br s, 1 H), 2.29 (s, 3 H),
2.62–2.92 (m, 1 H), 3.64–3.82 (m, 1 H), 3.91–3.95 (m, 1 H),
5.45 (br s, 1 H), 5.91 (s, 1 H), 6.17 (s, 1 H). 13C NMR (100
MHz, CDCl3): d = 13.80, 19.44, 23.70, 23.98, 25.57, 43.36,
46.31, 68.41, 69.85, 85.72, 106.34, 107.49, 151.54, 153.79.
HRMS (ESI): m/z calcd for [C14H23NO3 + Na]+: 276.1576;
found: 276.1575.
10e: [a]D = –52.6 (c 1.26, CHCl3). IR (thin film): 3402,
2955, 2929, 2870, 1446, 1368 cm–1. 1H NMR (500 MHz,
CDCl3): d = 0.82–0.85 (m, 6 H), 1.20 (d, 3 H, J = 6.3 Hz),
1.46–1.54 (m, 1 H), 1.73 (m, 1 H), 1.85 (dd, 1 H, J = 13.9,
5.6 Hz), 2.04–2.06 (m, 1 H), 2.11–2.17 (m, 1 H), 2.80–2.88
(m, 1 H), 3.74 (m, 1 H), 3.89–3.94 (m, 1 H), 5.54 (br s, 1 H),
6.96–6.99 (m, 2 H), 7.23 (dd, 1 H, J = 4.6, 1.8 Hz). 13C NMR
(100 MHz, CDCl3): d = 19.68, 23.93, 24.03, 25.27, 46.88,
49.25, 69.71, 70.43, 85.22, 124.10, 124.54, 126.87, 148.85.
HRMS (ESI): m/z calcd for [C13H21NO2S + Na]+: 278.1191;
found: 278.1182.
14c: mp 108–110 °C. IR (thin film): 3361, 29.18, 1714,
1490, 1043 cm–1. 1H NMR (500 MHz, CD3OD): d = 0.72 (d,
3 H, J = 6.6 Hz), 0.76 (d, 3 H, J = 6.6 Hz), 1.40 (s, 9 H),
1.57–1.66 (m, 1 H), 1.95–2.03 (m, 2 H), 3.02 (d, 1 H,
J = 14.4 Hz), 3.16 (d, 1 H, J = 14.4 Hz), 6.22 (dd, 1 H,
J = 3.2, 0.7 Hz), 6.35 (dd, 1 H, J = 3.2, 1.7 Hz), 7.40 (dd, 1
H, J = 1.7, 0.7 Hz). 13C NMR (125 MHz, CD3OD): d =
24.40, 25.05, 28.68, 31.12, 41.16, 46.84, 57.60, 80.15,
106.77, 111.35, 142.02, 156.37, 157.42, 173.88. HRMS
(ESI): m/z calcd for [C16H25NO5 + Na]+: 334.1630; found:
334.1629.
14d: mp 95–97 °C. IR (thin film): 3313, 2956, 1714, 1165
cm–1. 1H NMR (500 MHz, CD3OD): d = 0.74 (d, 3 H, J = 6.6
Hz), 0.77 (d, 3 H, J = 6.6 Hz), 1.40 (s, 9 H), 1.58–1.64 (m, 1
H), 1.90–1.99 (m, 2 H), 2.23 (s, 3 H), 2.99 (d, 1 H, J = 15.0
Hz), 3.09 (d, 1 H, J = 14.6 Hz), 5.90 (dd, 1 H, J = 2.9, 1.1
Hz), 6.04 (d, 1 H, J = 3.3 Hz). 13C NMR (125 MHz,
CD3OD): d = 13.40, 24.31, 24.45, 25.08, 28.71, 41.63,
46.82, 57.57, 80.23, 107.17, 107.38, 151.57, 155.45, 156.37,
174.53. HRMS (ESI): m/z calcd for [C17H27NO5 + Na]+:
348.1787; found: 348.1784.
14e: mp 127–129 °C. IR (thin film): 3024, 2924, 1712, 1649,
1394, 1170 cm–1. 1H NMR (400 MHz, CD3OD): d = 0.71 (d,
3 H, J = 6.6 Hz), 0.85 (d, 3 H, J = 6.6 Hz), 1.37 (s, 9 H),
1.61–1.70 (m, 1 H), 1.87 (dd, 1 H, J = 14.0, 5.5 Hz), 2.20
(dd, 1 H, J = 13.9, 5.5 Hz), 3.00 (d, 1 H, J = 1.4 Hz), 3.24 (d,
1 H, J = 14.4 Hz), 6.88–6.91 (m, 2 H), 7.23 (dd, 1 H, J = 4.6,
1.5 Hz). 13C NMR (125 MHz, C6D6): d = 23.99, 24.35,
24.69, 27.90, 30.17, 50.33, 58.83, 81.56, 123.13, 123.55,
126.15, 151.49, 158.20, 174.61. HRMS (ESI): m/z calcd for
[C13H25NO4 + Na]+: 350.1402; found: 350.1401.
15a: mp 100–102 °C. IR (thin film): 3304, 2974, 1706, 1164
cm–1. 1H NMR (500 MHz, CD3OD): d = 0.84 (t, 3 H, J = 7.5
Hz), 1.18 (s, 3 H), 1.44 (s, 9 H), 1.52–1.61 (m, 1 H), 2.37–
2.46 (m, 1 H), 4.49 (s, 1 H), 7.23–7.29 (m, 3 H), 7.36–7.39
(m, 2 H). 13C NMR (125 MHz, CDCl3): d = 7.84, 20.29,
28.38, 28.77, 56.47, 57.62, 79.11, 127.52, 128.00, 130.06,
134.84, 154.24, 177.18. HRMS (ESI): m/z calcd for
[C17H25NO4 + Na]+: 330.1681; found: 330.1672.
11a: Mp 72–74 °C. IR (thin film): 3343, 3217, 2969, 1455
cm–1. 1H NMR (400 MHz, CDCl3): d = 0.73 (t, 3 H, J = 7.4
Hz), 0.86 (d, 3 H, J = 6.2 Hz), 0.88–0.99 (m, 1 H), 1.09–1.22
(m, 1 H), 1.41 (s, 3 H), 2.00–2.50 (br s, 1 H), 3.16 (d, 1 H,
J = 5.5 Hz), 3.71–3.74 (m, 1 H), 4.24–4.27 (m, 1 H), 5.54–
6.02 (br s, 1 H), 7.12–7.18 (m, 2 H), 7.24–7.35 (m, 3 H). 13
C
NMR (100 MHz, CDCl3): d = 8.70, 18.19, 24.91, 27.74,
59.28, 67.96, 68.53, 89.18, 127.10, 128.34, 129.80, 136.16.
HRMS (ESI): m/z calcd for [C14H21NO2 + Na]+: 258.1470;
found: 258.1469.
Synlett 2004, No. 8, 1409–1413 © Thieme Stuttgart · New York