Organic Syntheses, Vol. 78, pp. 160-168
Checked by Ruth Figueroa and David J. Hart.
1. Procedure
B. 4-Hydroxymethyl-3-dimethylamino-1-tert-butyldimethylsiloxy-1-cyclohexene,
3. A
dry, 500-mL, three-necked, round-bottomed flask
is equipped with a
150-mL pressure-equalizing addition funnel,
a
reflux condenser topped with an inert atmosphere line, a
glass stopper, and an
egg-shaped magnetic stirring
bar. The flask is charged with
lithium
aluminum hydride (2.66 g, 0.070 mol)
and
anhydrous ether (50 mL) (Note
1). The flask is cooled to 5°C in an
ice-water bath.
A solution of
cycloadduct 2 (22.4 g,
0.072 mol) in
ether (80
mL) is transferred to the addition funnel and added over a 30-min
period. The reaction mixture is stirred for another 15 min, diluted with
ether (100 mL), and quenched by dropwise
addition of water (9 mL). The
ice-water bath is removed, the
resulting gray suspension is allowed to reach room temperature, and the mixture is
stirred vigorously for an additional 60 min. The mixture is transferred to a
1.0-L
Erlenmeyer flask and diluted with
350
mL of ether.
Anhydrous sodium
sulfate (Na2SO4) (60 g) is
added, the suspension is stirred for 30 min, and filtered. The filter cake is washed
twice with
ether (50 mL each time).
The solvent is removed on a
rotary evaporator and the remaining
volatile material is removed under high vacuum to afford
18.6 g (
91%)
of the desired amino alcohol
3 as a viscous clear oil (Note
4).
2. Notes
1.
Anhydrous ether was purchased from Fisher
Scientific Company and was not further purified.
2.
Methyl acrylate
was purchased from Aldrich Chemical Company, Inc.,
and used without further purification.
3. The cycloadduct consists of a 1.5:1.0 mixture of trans- and cis-diastereomers:
1H NMR of cis-diastereomer
(300 MHz, CDCl
3) δ: 0.16 (s, 6 H), 0.93 (s, 9
H), 1.83 (m, 1 H), 2.0-2.2 (m, 3 H), 2.27 (s,
6 H), 2.62 (m, 1 H), 3.56 (dd, 1 H, J = 5.0, 5.0),
3.70 (s, 3 H), 4.95 (d, 1 H, J = 5.0);
13C NMR (75 MHz, CDCl
3)
δ: −4.4, 18.0, 20.9, 25.6,
28.9, 43.5, 44.8, 51.3, 59.2
100.7, 153.7, 174.6;
1H NMR of trans-diastereomer (300 MHz, CDCl
3)
δ: 0.14 (s, 3 H), 0.15 (s, 3 H), 0.92 (s, 9
H), 1.7-2.0 (m, 2 H), 2.0-2.2 (m, 2 H), 2.24
(s, 6 H), 2.52 (ddd, 1 H, J = 12.7, 9.2, 3.8), 3.66 (m,
1 H), 3.70 (s, 3 H), 4.84 (dd, 1 H, J = 2.0, 1.8);
13C NMR (75 MHz,
CDCl
3) δ: −4.5, −4.3, 18.0,
25.5, 25.6, 29.0, 40.6, 42.3,
51.7, 61.9, 102.6, 152.4, 176.0.
4. This material is a mixture of diastereomers. Selected peaks from
each diastereomer follow:
1H
NMR of major diastereomer (400 MHz, C
6D
6) δ: 0.98
(s, 9 H, CMe
3), 1.99 (s, 6 H, NMe
2), 4.81
(broad s, 1 H, =CH);
13C NMR (75 MHz, CDCl
3) δ: −4.4,
18.0, 20.9, 25.6, 28.9, 43.5,
44.8, 51.3, 59.2, 100.7, 153.7,
174.6;
1H
NMR of minor diastereomer (400 MHz, CDCl
3) δ: 1.01 (s, 9 H,
CMe
3), 2.05 (s, 6 H, NMe
2), 4.99 (d,
1 H, J = 4, =CH);
13C NMR (75 MHz, CDCl
3) δ: −4.0,
−3.8, 18.5, 25.2, 30.1,
39.5, 44.4, 62.0, 44.2, 100.4,
155.0 (one peak not observed).
5. A
4.0 M solution of HF in
THF was prepared in a
50-mL plastic bottle by the addition
of
4.1 mL of the 49%
aqueous HF solution (using a
disposable plastic syringe)
to
THF (28 mL).
6. In order to minimize bumping, a
250-mL, round-bottomed
flask was used for the distillation.
7. The checkers obtained
5.72
g (
81%) of the enone.
This compound displays the following spectral data: IR
(neat) cm
−1: 3420, 1675;
1H NMR (300 MHz, CDCl
3)δ:
1.60 (m, 1 H, OH), 1.82 (dddd, 1 H, J = 12.6, 12.6, 9.8, 5.0),
2.14 (dddd, 1 H, J = 12.6, 9.7, 5.0, 1.3), 2.42 (ddd, 1 H, J =
16.8, 12.6, 5.0), 2.56 (ddd, 1 H, J = 16.8, 5.0, 5.0), 2.65
(m, 1 H), 3.71 (m, 2 H), 6.08 (dd, 1 H, J = 10.0, 2.2),
6.96 (ddd, 1 H, J = 10.0, 2.7, 1.3);
13C NMR (75 MHz, CDCl
3)δ:
25.3, 36.6, 38.9, 65.1, 130.2,
151.5, 199.9; mass
spectrum (EI) 126 (C
7H
10O
2);
96 (base).
All toxic materials were disposed of in accordance with "Prudent Practices in the
Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
The three-step procedure above illustrates the usefulness of a
1-amino-3-siloxy
diene for the synthesis of functionalized cyclohexenones and
is representative of the general usefulness of the dienes. The first step in the sequence,
the Diels-Alder reaction between the parent aminosiloxy diene and
methyl
acrylate, cleanly produces the cycloadduct, as a mixture of endo and exo diastereomers.
This diene also reacts with many other dienophiles and the results are summarized
in Table I.
3 The cycloadducts are generally obtained as mixtures of endo-exo
diastereomers, except for the reactions with
N-phenylmaleimide
and
methacrolein, which proceed
with high endo selectivity, and with
dimethyl maleate,
which gives predominantly the exo adduct.
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