Pd-Catalyzed Asymmetric Diene Cyclization/Hydrosilylation
J . Org. Chem., Vol. 66, No. 23, 2001 7645
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tr a n s-3-(3-t-Bu tyl-3,3-d ip h en yl-1,1-d im eth yld isiloxy)-
m eth yl-1,1-d ica r bom eth oxy-4-m eth ylcyclop en ta n e (5e).
Diene 1 (170 mg, 0.80 mmol) and HSiMe2OSiPh2-t-Bu (0.75 g,
2.5 mmol) were added sequentially to a solution of (R)-2 (15
mg, 0.04 mmol) and NaBAr4 (36 mg, 0.04 mmol) in CH2Cl2 (9
mL) under nitrogen at -20 °C and maintained at this
temperature for 12 h. Evaporation of solvent and chromatog-
raphy (hexanes-EtOAc ) 55:1 f 25:1) gave 5e (420 mg, 100%)
F or 11b. H NMR: δ 3.93 (s, 4 H), 3.74 (dd, J ) 3.8, 10.6
Hz, 1 H), 3.51 (dd, J ) 6.2, 10.6 Hz, 1 H), 1.83 (m, 2 H), 1.52
(m, 2 H), 1.50 (s, 1 H), 1.32 (dd, J ) 10.2, 13.4 Hz, 1 H), 1.19
(s, 18 H), 1.14 (m, 1 H), 1.01 (d, J ) 6.0 Hz, 3 H).13C{1H}
NMR: δ 178.8, 68.3, 68.0, 65.3, 49.1, 44.4, 41.8, 39.3, 36.6,
36.1, 27.5, 18.9. IR (neat, cm-1): 3444, 2957, 2870, 1730, 1480,
1397, 1364, 1283, 1152, 1028. Anal. Calcd (found) for C19
34O5: C, 66.63 (66.19); H, 10.01 (9.88).
Oxid a tion of 3-(3-ter t-Bu tyl-3,3-d ip h en yl-1,1-d im eth -
-
H
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as a colorless oil. H NMR: δ 7.72-7.61 (m, 4 H), 7.42-7.33
(m, 6 H), 3.69 (s, 3 H), 3.68 (s, 3 H), 2.56 (dd, J ) 6.8, 13.6 Hz,
1 H), 2.46 (dd, J ) 6.8, 13.6 Hz, 1 H), 1.68 (dd, J ) 10.8, 13.6
Hz, 1 H), 1.63 (dd, J ) 6.8, 13.6 Hz, 1 H), 1.48-1.39 (m, 2 H),
1.03 (s, 9 H), 0.98 (dd, J ) 2.2, 14.8 Hz, 1 H), 0.87 (d, J ) 6.0
Hz, 3 H), 0.37 (dd, J ) 11.2, 14.8 Hz, 1 H), 0.12 (s, 3 H), 0.11
(s, 3 H). 13C{1H} NMR: δ 173.8, 173.6, 136.3, 135.4, 129.7,
127.8, 58.5, 52.9, 43.8, 43.0, 42.9, 42.4, 27.1, 22.5, 19.5, 17.4,
2.0, 1.5. IR (neat, cm-1): 3062, 2953, 2857, 1961, 1888, 1827,
1735, 1428, 1256, 1117, 1047, 839, 819. HRMS (EI): calcd
(found) for C28H39O5Si2 (M+ - CH3) 511.2336 (511.2344).
The conversion of 1 to 5b-g (Table 2), 7 to 11c, 16 to 20a ,
17 to 21a , 18 to 22a , 19 to 23a , 24 to 25a (Table 1, entries 2
and 6-10), 26 to 27a , 7 to 11d , 16 to 20c, 17 to 21c, 31 to
32a , 33 to 34a , 35 to 38a , 36 to 39a , 37 to 40a , 41 to 42a , 43
to 44a (Table 3), and 28 to 29 (Scheme 6) were performed
employing a procedure similar to that used to synthesize 5e.
Spectral data for these silylated carbocycles are included in
the Supporting Information.
Oxid a tion of 5e. A suspension of 5e (440 mg, 0.83 mmol)
and TBAF (1.0 M in THF, 7.0 mL, 7.0 mmol) was stirred at
room temperature for 19 h. Solvent was evaporated, and the
resulting viscous oil was dissolved in DMF (5 mL), treated with
KF (470 mg, 8.0 mmol) and AcOOH (32wt % in AcOH) (2.6
mL, 12.0 mmol), and stirred at room temperature for 7 h.
Water (5 mL) was added and the mixture was extracted with
ethyl acetate. The combined organic extracts were washed with
1 N HCl, saturated aqueous NaHCO3, 10% Na2SO3/H2O, and
brine, dried (MgSO4), filtered, concentrated under vacuum, and
chromatographed (hexane/EtOAc ) 20:1 f 2:1) to give 6 (92
mg, 48%) as a colorless oil.
yld isiloxy)m et h yl-1,1-b is(m et h oxym et h yl)-4-m et h ylcy-
clop en ta n e (21a ). A suspension of 21a (325 mg, 0.65 mmol),
TBAF (1.0 M in THF, 7.0 mL, 7.0 mmol), KHCO3 (100 mg, 1.0
mmol), and H2O2 (50wt % in water, 0.75 mL, 13.0 mmol) in
MeOH (3 mL) was refluxed for 24 h. Water/EtOAc workup
followed by chromatography gave trans-1,1-bis(methoxym-
ethyl)-3-hydroxymethyl-4-methylcyclopentane (21b) (100 mg,
76%) as a colorless oil. Carbocycles 20a and 23a were oxidized
employing a similar procedure (Table 1, entries 6 and 9).
Spectral data for alcohols 20b and 23b are included in the
Supporting Information.
1
F or 21b. H NMR: δ 3.67 (dd, J ) 4.0, 10.8 Hz, 1 H), 3.46
(dd, J ) 6.4, 10.4 Hz, 1 H), 3.30 (d, J ) 1.2 Hz, 6 H), 3.19 (d,
J ) 3.4 Hz, 4 H), 1.95 (s, 1 H), 1.75 (m, 2 H), 1.64 (m, 2 H),
1.22 (dd, J ) 10.0, 13.2 Hz, 1 H), 1.05 (dd, J ) 10.0, 12.6 Hz,
1 H), 1.96 (d, J ) 6.0 Hz, 3 H). 13C{1H} NMR: δ 78.3, 78.1,
65.7, 59.5, 49.2, 45.8, 42.3, 36.8, 36.3, 19.0. IR (neat, cm-1):
3409 (O-H). Anal. Calcd (found) for C11H22O3: C, 65.31 (64.89);
H, 10.96 (10.68).
4-Ca r bom eth oxy-1-tr ieth ylsilylm eth yl-2-m eth ylcyclo-
p en ta n e (15). A suspension of 3 (95 mg, 0.29 mmol) and TBAF
(1.0 M in THF, 3.5 mL, 3.5 mmol) was stirred at room
temperature for 2 days. Evaporation of solvent and chroma-
tography (hexanes-EtOAc ) 50:1 f 25:1) gave 15 (60 mg,
77%) as a pale yellow oil. The 1H NMR spectrum of 15 was
identical to an authentic sample.37b
Deter m in a tion of En a n tiom er ic Excess a n d Absolu te
a n d Rela tive Con figu r a tion . The enantiomeric excess of
carbocycles 5a -g, 12a , 13a , 14a , 29, 32a , 34a , 39a , and 40a
1
was determined by H NMR spectroscopy employing Eu(hfc)3
Oxid a tion of 3-(Ben zh yd r yld im eth ylsilyl)m eth yl-1,1-
d ica r bom eth oxy-4-m eth ylcyclop en ta n e (5f). A suspension
of 5f (350 mg, 0.81 mmol), TBAF (1.0 M in THF, 9.7 mL, 9.7
mmol), KHCO3 (160 mg, 1.6 mmol), and H2O2 (50wt % in
water, 0.94 mL, 16 mmol) in MeOH/EtOAc (10:1, 4.4 mL) was
stirred at room temperature for 21 h. Water/EtOAc workup
and chromatography (hexanes-EtOAc ) 23:1 f 2:1) gave 6
(149 mg, 80%) as a colorless oil. Carbocycles 27a , 32a , 34a ,
39a , 40a , 42a , and 44a were oxidized employing an analogous
procedure (Table 3, entries 1, 5, 6, and 8-11). Carbocycles 11d ,
20c, 21c, and 38a were oxidized employing a procedure
analogous to that used to oxidize 5f except that no ethyl
acetate was present in the reaction mixture (Table 3, entries
2-4 and 7). Spectral and analytical data for alcohols 11b, 20b,
21b, 32b, 27b, 34b, 38b, 39b, 40b, 42b, and 44b are included
in the Supporting Information.
as a chiral shift reagent. The enantiomeric excess of car-
bocycles 11b, 20b, 22b, 23b, 25b, 27b, 38b, 42b, and 44b was
1
determined by H and 19F NMR analysis of the corresponding
Mosher ester. The enantiomeric excess of carbocycle 21b was
determined by chiral GC analysis on a 20 m × 0.25 mm
Chiraldex G-TA column (Advanced Separation Technologies).
In each case, the peaks corresponding to the enantiomeric pair
were identified from the corresponding racemic carbocycle. The
relative and absolute stereochemistry of trans-(S,S)-6 formed
from 5a , 5e, and 5f was established by comparison to an
authentic sample.11b The absolute stereochemistry of the
remaining carbocycles was assigned by analogy to carbocycle
trans-(S,S)-6. The relative stereochemistry of the remaining
carbocycles was assigned based on the relative stereochemistry
of the analogous triethylsilyl-substituted carbocycles.37
Oxid a tion of 3-(3-ter t-Bu tyl-3,3-d ip h en yl-1,1-d im eth -
yld isiloxy)m eth yl-1,1-bis(tr im eth yla cetoxym eth yl)-4-m e-
th ylcyclop en ta n e (11c). A solution of 11c (360 mg, 0.57
mmol), TBAF (1.0 M in THF, 5.0 mL, 5 mmol), KF (410 mg,
7.0 mmol), KHCO3 (120 mg, 1.2 mmol), and H2O2 (50wt %,
0.70 mL, 12.0 mmol) in MeOH (3 mL) was stirred at room
temperature for 3 days. Water/EtOAc workup followed by
chromatography (hexanes-EtOAc ) 25:1 f 2:1) gave trans-
1,1-bis(trimethylacetoxymethyl)-3-hydroxymethyl-4-methyl-
cyclopentane (11b) (143 mg, 73%) as a colorless oil. Carbocycles
22a and 25a were oxidized employing a similar procedure
(Table 1, entries 8 and 10). Spectral and analytical data for
alcohols 22b and 25b are included in the Supporting Informa-
tion.
Ack n ow led gm en t is made to the National Institutes
of Health (GM59830-01) for support of this research.
R.W. thanks DuPont for a Young Professor Award, the
Alfred P. Sloan Foundation for a research fellowship,
and the Camille and Henry Dreyfus Foundation for new
faculty and Teacher-Scholar awards.
Su p p or tin g In for m a tion Ava ila ble: Analytical and spec-
troscopic data for new compounds and experimental procedure
for the synthesis of 35. This material is available free of charge
J O015724N