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DOI: 10.1055/s-0029-1217755
Synthesis of 2,2-Disubstituted Pentalenes and Indenes by a Useful Modification to Nakamura’s DMCP [3+2]-Cycloaddition Protocol
Publication History
Publication Date:
04 September 2009 (online)
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Abstract
A two-pot tactic is presented to reach the oxidized 2,2-dimethyl-substituted pentalene and indene ring systems.
Key words
illudin - trimethylenemethane - [3+2]-cycloaddition - 5,6-fused-ring systems - indene - pentalene - ketene acetal methylation
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References and Notes
Preparation of
15; Representative Procedure for Ester 15c:
Compounds 11c (0.123 g, 0.489 mmol) and 10 (0.038 g, 0.246 mmol) were dissolved
in CD3CN (0.500 mL) and heated in a sealed NMR tube at
80 ˚C for 0.5 h. Additional 10 (0.100
g, 0.648 mmol) was added to the reaction mixture and it was heated
for 2 h. After cooling to r.t., MeI (0.150 mL, 2.41 mmol) was added
and the reaction mixture was heated to 80 ˚C for 24 h.
Afterwards, the mixture was concentrated in vacuo and purified by
silica gel chroma-tography (75% CH2Cl2-hexanes)
to afford 15c as a light yellow oil (0.074
g, 41% based on recovered starting material); R
f
= 0.22
(75% CH2Cl2-hexanes). ¹H
NMR (500 MHz, CDCl3): δ = 7.47 (d, J = 7.1 Hz, 2 H), 7.36 (d, J = 6.8 Hz, 1 H), 7.30 (t, J = 7.9 Hz, 2 H), 3.84 (q, J = 10.5 Hz, 2 H), 3.12-3.17
(m, 3 H), 2.75 (m, 1 H), 2.13-2.28 (m, 3 H), 1.99 (m, 2
H), 1.86 (d, J = 14.4 Hz, 1
H), 1.64 (m, 3 H), 1.37 (s, 3 H), 1.05 (s, 6 H). ¹³C
NMR (125 MHz, CDCl3): δ = 205.7, 177.2,
136.8, 129.5, 129.3, 129.1, 71.3, 47.2, 47.1, 46.4, 40.7, 37.3,
34.7, 27.1, 24.8, 24.5, 24.4, 22.2, 19.3. IR (thin film): 3505,
2959, 2932, 2870, 1728, 1693, 1462, 1207, 1134, 741 cm-¹.
HRMS: m/z calcd
for C22H29IO3Se: 548.0327; found:
548.0340.
Selected data of ortho-ester 14d: R
f
= 0.20 (5% EtOAc-hexanes). ¹H
NMR (500 MHz, CDCl3): δ = 6.30 (t, J = 4.1 Hz, 1 H), 5.48 (t, J = 2.4 Hz, 1 H), 5.17 (t, J = 2.4 Hz, 1 H), 4.09 (d, J = 10.3 Hz, 1 H), 4.01 (d, J = 10.3 Hz, 1 H), 3.42 (m,
2 H), 3.14 (dt, J = 16.1, 2.7
Hz, 1 H), 2.53 (dt, J = 16.1, 1.9
Hz, 1 H), 2.15 (m, 1 H), 2.06 (m, 2 H), 1.90 (m, 1 H), 1.81 (m,
1 H), 1.63 (m, 1 H), 1.26 (s, 3 H), 0.78 (s, 3 H).
Selected
data for exocyclic methylene adduct 13e: R
f
= 0.28 (10% EtOAc-hexanes). ¹H
NMR (500 MHz, CDCl3): δ = 5.50 (t, J = 2.4 Hz, 1 H), 5.25 (t, J = 2.1 Hz, 1 H), 3.66 (m, 1 H),
3.59 (m, 2 H), 3.40 (d, J = 11.3
Hz, 1 H), 2.87 (m, 2 H), 2.68 (m, 3 H), 2.27 (dd, J = 16.8,
2.7 Hz, 1 H), 1.98 (m, 1 H), 1.87 (m, 1 H), 1.75 (m, 1 H), 0.94
(s, 3 H), 0.93 (s, 3 H).
Preparation
of 16 and 17; Representative Procedure from
Bromide: Compound 12d (0.010 g, 0.021
mmol) was dissolved in THF (1.0 mL) and cooled to 0 ˚C.
To the solution was added DBN (0.020 mL, 0.162 mmol) and the reaction
was stirred at 0 ˚C to r.t. for 14 h. The reaction mixture
was filtered through a pad of silica gel then concentrated in vacuo.
The crude residue was purified by silica gel chromatography (15% EtOAc-hexanes)
to afford 16 as a colorless oil (0.0060
g, 72% yield, 40% overall yield from 11d).
Data for compound 16: R
f
= 0.10 (20% EtOAc-hexanes).
¹H
NMR (500 MHz, CDCl3): δ = 3.95 (s,
2 H), 3.21 (d, J = 16.4 Hz,
1 H), 3.18 (s, 2 H), 2.93 (d, J = 16.2
Hz, 1 H), 2.74 (s, 2 H), 2.55 (s, 2 H), 2.45 (d, J = 18.8
Hz, 1 H), 2.36 (d,
J = 16.1
Hz, 1 H), 1.44 (s, 3 H), 1.09 (s, 6 H). ¹³C
NMR (125 MHz, CDCl3): δ = 203.7, 183.4,
176.6, 146.1, 71.6, 54.2, 43.9, 40.8, 37.2, 34.7, 26.7, 26.0, 24.3,
18.6. IR (thin film): 2962, 2928, 1732, 1697, 1643, 1377, 1215,
1169, 1111
cm-¹. HRMS: m/z calcd
for C15H21IO3Na: 399.0433; found: 399.0430.
Procedure from Phenyl Selenide: Compound 15c (0.027 g, 0.049 mmol) was dissolved
in CH2Cl2 (1.0 mL). To the solution was added
H2O (0.020 mL) followed by H2O2 (30% w/w
in H2O, 0.13 mL, 0.104 mmol). The reaction was then stirred
for 1.5 h. The reaction was quenched with sat. aq NaHCO3 and
diluted with CH2Cl2. The aqueous layer was extracted
with CH2Cl2 (3 ×) and the combined
organics were washed with brine, dried (Na2SO4),
and concentrated in vacuo. The crude residue was purified by silica
gel chromatography (15% EtOAc-hexanes) to afford 17 as a colorless oil (0.014 g, 74% yield).
Data
for compound 17: R
f
= 0.14 (15% EtOAc-hexanes).
¹H
NMR (500 MHz, CDCl3): δ = 3.93 (s,
2 H), 3.23 (dt, J = 2.3, 14.0
Hz, 1 H), 3.18 (s, 1 H), 3.04 (dt, J = 2.3,
14.0 Hz, 1 H), 2.54 (d, J = 13.9
Hz, 1 H), 2.45 (d, J = 14.0
Hz, 1 H), 2.41 (m, 2 H), 2.34 (m, 2 H), 2.06 (quint, J = 6.5 Hz, 2 H), 1.39 (s, 3
H), 1.09 (s, 3 H). ¹³C NMR (125 MHz,
CDCl3): δ = 197.6, 177.0, 162.6, 135.5,
71.4, 48.9, 47.1, 41.4, 37.7, 34.7, 26.6, 26.2, 24.3, 23.5, 18.7.
IR (thin film): 2962, 2978, 2870, 1732, 1666, 1393, 1184 cm-¹.
HRMS: m/z calcd
for C16H23IO3Na: 413.0590; found:
413.0595.
Preparation of 18 and 19; Representative Procedure from Ester 17:
To a cooled (-78 ˚C) solution of 17 (0.016 g,
0.041 mmol) in toluene (0.5 mL) was added DIBAL-H
(1 M
in hexanes, 0.246 mL, 0.246 mmol). The resulting solution was stirred
at -78 ˚C for 1 h. The reaction was quenched with
1 M aq Rochelle’s salt, diluted with EtOAc, and stirred
vigorously for 1 h. The aqueous layer was extracted with EtOAc (4 ×).
The combined organics were washed with brine, dried with Na2SO4 and
concentrated in vacuo to afford an inconsequential mixture (ca.
1:1) of allylic alcohols. The crude product was sufficiently pure
for the subsequent reaction. However, the mixture of allylic alcohols
could be separated by silica gel chromatography (40% EtOAc-hexanes → 75% EtOAc-hexanes)
with R
f
= 0.55
and 0.48 (75% EtOAc-hexanes) (combined mass of 0.0060
g, 86% yield).
The crude mixture of allylic alcohols
(0.0060 g, 0.033 mmol) was dissolved in CH2Cl2 (1.0
mL). MnO2 (0.069 g, 0.78 mmol) was added to the flask
and the reaction was stirred at r.t. for 12 h. The mixture was filtered
through Celite and concentrated in vacuo. The crude residue was purified
by silica gel chromatography (40% EtOAc-hexanes → 50% EtOAc-hexanes)
to afford 19 as a colorless oil (0.0049
g, 83% yield).
Data for compound 19: R
f
= 0.15
(40% EtOAc-hexanes).
¹H
NMR (500 MHz, CDCl3): δ = 3.46 (s,
2 H), 2.67 (d, J = 18.4 Hz,
1 H), 2.49 (d, J = 15.6 Hz,
1 H), 2.38 (m, 2 H), 2.22-2.35 (m, 4 H), 2.04 (quint, J = 6.6 Hz, 2 H), 1.13 (s, 3
H). ¹³C NMR (125 MHz, CDCl3): δ = 164.1,
136.3, 70.8, 47.7, 42.4, 39.5, 37.7, 26.9, 25.1, 23.6 (C=O
carbon unresolved).
IR (thin film): 3413, 2924, 2854,
1651, 1393, 1045 cm-¹. HRMS: m/z calcd
for C11H16O2: 180.1150; found:
180.1148.