9338 J . Org. Chem., Vol. 62, No. 26, 1997
Notes
and tert-butyldiphenylchlorosilane (0.59 g, 2.15 mmol, 1.0 equiv),
and the reaction mixture was allowed to warm to room temper-
ature over a 12-h period. The reaction mixture was diluted with
H2O (15 mL) and the mixture extracted with Et2O (2 × 25 mL),
dried (MgSO4), and concentrated in vacuo. Purification on SiO2
(Petroleum Ether) afforded 4a as a colorless oil, 0.65 g (90%,
0.72 g theoretical): 1H NMR (400 MHz, CDCl3) δ 7.68-7.30 (m,
10H), 5.52 (s, 2H), 3.98 (m, 1H), 2.65 (m, 1H), 2.43 (dd, 1H, J 1
) 6.4 Hz, J 2 ) 1.6 Hz), 2.37 (dd, 1H, J 1 ) 1.2 Hz, J 2 ) 2.8 Hz),
(1.04, s, 9H), 0.72 (d, 3H, J ) 6.8 Hz); 13C NMR (75.5 MHz,
CDCl3) δ 135.9, 135.1, 134.8, 133.0, 129.5, 129.3, 127.7, 127.5,
80.8, 49.1, 41.7, 27.0, 19.2, 17.9, 0.87; IR (neat) νmax 3136, 3090,
3070, 3000, 2958, 2931, 2898, 1657, 1487, 1364, 1119; CIMS
(NH3 gas) 337.3, 296.2, 279.2, 199.1, 81.0; CIHRMS M + H+
calcd for C22H29SiO 337.1987, found 337.1952; [R]23D ) +23.8 (c
) 0.63, CHCl3).
the mixture extracted with CH2Cl2 (2 × 25 mL), dried (MgSO4),
and concentrated in vacuo. The crude cyclohexenol was redis-
solved in 3.7 mL of CH2Cl2 (0.1 M) and the solution cooled to 0
°C. To this solution were added 2,6-lutidine (0.13 mL, 1.11
mmol, 3.0 equiv) and TBSOTf (0.13 mL, 0.56 mmol, 1.5 equiv),
and the reaction mixture was stirrred at 0 °C for 2 h. The
reaction mixture was diluted with H2O (10 mL) and the mixture
extracted with CH2Cl2 (2 × 25 mL), dried (MgSO4), and
concentrated in vacuo. Purification on SiO2 (petroleum ether)
afforded 5a as a colorless oil, 0.075 g (90%, two steps): 1H NMR
(400 MHz, CDCl3) δ 5.56-5.53 (m, 1H), 5.52-5.48 (m, 1H), 3.94-
3.90 (m, 1H), 2.23-2.22 (m, 1H), 2.10-1.95 (m, 2H), 1.72-1.65
(m, 1H), 1.57-1.42 (m, 1H), 0.97 (d, 3H, J ) 7.2 Hz), 0.37 (s,
3H), 0.32 (s, 9H), 0.059 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ
127.7, 125.6, 70.4, 35.5, 27.5, 23.7, 15.5, 1.02, 0.85, -1.05, -1.16;
ΙR (neat) νmax 3420, 3070, 3022, 2959, 1653, 1428, 1254, 1119;
CIMS (NH3 gas) 209.0, 135.0, 105.0, 95.0, 67.0; CIHRMS M +
H+ calcd for C13H27SiO 227.1832, found 227.1848; [R]23D ) +25.0
(c ) 0.38, CHCl3).
R ep r esen t a t ive E xp er im en t a l P r oced u r e for t h e
BF 3‚OEt2-Med ia ted Am in oca r bocycliza tion of th e Ch ir a l
(E)-Cr otylsilyl Ald eh yd es 2. (3S,4S)-3-Meth yl-4-[N-(p-tolu -
en esu lfon yl)a m in o]cyclop en ten e (6a ). To a cooled solution
of 2a (0.100 g, 0.45 mmol) and p-TsNH2 (0.078 g, 0.45 mmol) in
CH2Cl2 (2 mL, 0.3 M) at -78 °C was added BF3‚OEt2 (0.11 mL,
0.90 mmol, 2.0 equiv). The reaction mixture was warmed to
room temperature, stirred for 10 min (the reaction mixture
becomes light yellow and homogeneous), and then recooled to
-35 °C. The reaction mixture was stirred for 24 h at -35 °C,
subsequently diluted with NaHCO3 solution, and stirred to room
temperature. The reaction mixture was extracted with CH2Cl2
(3 × 25 mL), dried (MgSO4), and concentrated in vacuo to afford
the crude aminocyclopentene. Purification on SiO2 (20% f 30%
EtOAc/PE) afforded 6a as a colorless oil, 0.090 g (80%, 0.11 g
theoretical): 1H NMR (400 MHz, CDCl3) δ 7.75 (d, 2H, J ) 8.0
Hz), 7.28 (d, 2H, J ) 8.4 Hz), 5.51 (s, 2H), 4.55 (d, 1H, J ) 8.8
Hz), 3.44-3.39 (m, 1H), 2.55-2.39 (m, 3H), 2.41 (s, 3H), 0.92
(d, 3H, J ) 17 Hz); 13C NMR (75.5 MHz, CDCl3) δ 134.7, 129.7,
127.4, 127.1, 60.7, 47.4, 39.7, 22.4, 21.6, 18.1, 14.1; ΙR (neat)
Rep r esen ta tive Exp er im en ta l P r oced u r e for th e P r ep a -
r a tion of th e Hom ologa ted Ch ir a l (E)-Cr otylsilyl Ad e-
h yd es 3. (4R)-(E)-4-(Dim eth ylp h en ylsilyl)-5-h ep ten a l (3a ).
To a stirred solution of (methoxymethyl)triphenylphosphonium
chloride (1.66 g, 4.84 mmol, 1.1 equiv) in THF (6.1 mL, 0.78 M)
at -10 °C was added dropwise lithium diisopropylamide (5.28
mmol, 1.2 equiv). The deep red solution was stirred at -10 °C
for 30 min, after which time a solution of 2a (1.02 g, 4.40 mmol)
in THF (11 mL, 0.40 M) was added. The reaction mixture was
stirred at -10 °C for 1 h, subsequently diluted with NaHCO3
solution, and stirred to room temperature. The reaction mixture
was extracted with Et2O (3 × 25 mL), dried (MgSO4), and
concentrated in vacuo leaving the crude enol ether which was
immediately dissolved in 18 mL of THF/H2O (10:1, 0.25 M). To
the stirred solution of enol ether was added mercuric acetate
(2.80 g, 8.80 mmol, 2.0 equiv) and the suspension was stirred
at room temperature for 1 h; the reaction mixture was subse-
quently diluted with 50 mL of a 7% aqueous KI solution. The
gray suspension was stirred at room temperature for 2 h,
extracted with Et2O (3 × 25 mL), dried (MgSO4), and concen-
trated in vacuo to afford the crude aldehyde. Purification on
SiO2 (2.5% EtOAc/PE) afforded 3a as a colorless oil (70%, two
steps, 0.76 g): 1H NMR (400 MHz, CDCl3) δ 9.67 (t, 1H, J ) 1.6
Hz), 7.47-7.45 (m, 2H), 7.35-7.33 (m, 3H), 5.26-5.21 (m, 1H),
5.14-5.08 (m, 1H), 2.49-2.42 (m, 1H), 2.33-2.25 (m, 1H), 1.78-
1.76 (m, 1H), 1.63 (dd, 3H, J ) 1.2 Hz), 1.56-1.54 (m, 2H), 0.26
(s, 3H), 0.24 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ 203.2, 134.0,
133.0, 130.6, 129.0, 127.7, 124.8, 43.7, 32.3, 21.6, 18.1, -4.34,
-5.38; ΙR (neat) νmax 3428, 3070, 3013, 2959, 1724, 1653, 1249;
CIMS (NH3 gas) 247.1, 231.1, 220.1, 211.1, 209.0, 205.1;
ν
max 3277, 3063, 2958, 1653, 1599, 1428, 1326, 1305, 1159; CIMS
(NH3 gas) 252.0, 96.0, 80.0; CIHRMS M + H+ calcd for C13H18
-
NO2S 252.1058, found 252.1056; [R]23 ) +40.8 (c ) 0.36,
CHCl3).
D
Ack n ow led gm en t. This work has been financially
supported by the National Institutes of Health
(RO1CA56304).
CIHRMS M+ calc for C15H22SiO 246.1440, found 246.1409; [R]23
) +9.14 (c ) 0.35, CHCl3).
D
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
data for all reaction products as well as full characterization
data for compounds 2b-j, 4b-f, 3b-d , 5b-d , and 6g-j (10
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
Rep r esen ta tive Exp er im en ta l P r oced u r e for th e TiCl4-
Med ia ted Ca r bocycliza tion of th e Ch ir a l (E)-Cr otylsilyl
Ald eh yd es 3. (3S,4S)-3-Meth yl-4-(ter t-bu tyld im eth ylsilyl)-
cycloh exen -4-ol (5a ). Silyl aldehyde 3a (0.090 g, 0.37 mmol)
was dissolved in 3.7 mL of CH2Cl2 (0.1 M) and the solution cooled
to -78 °C under argon. To this solution was added freshly
distilled TiCl4 (0.045 mL, 0.41 mmol, 1.1 equiv), and the deep
red homogeneous solution was stirred for 1 h at -78 °C. After
1 h, the reaction mixture was diluted with H2O (10 mL) and
J O970832O