M. Sada, S. Matsubara / Tetrahedron 67 (2011) 2612e2616
FeCl2 + Me2Mg (4g)
2615
OH
(2.0 equiv) (1.5 equiv)
OMe
Me
0 °C
Me
OH
Me
O
O
10 (84%)
11 (52%)
OMe
Me
Me2Mg (4g)
(1.5 equiv)
Me
Me
O
9 (1.0 equiv)
Me
0 °C
OH
Scheme 3. Reaction of FeCl2eMe2Mg and Me2Mg with ketoester 9.
Unless otherwise noted, commercially available reagents were
used without purification. Tetrahydrofuran, Dehydrated stabilizer
free dSuperd was purchased from Kanto Chemical Co., stored
under argon, and used as it is.
Table 4
Reaction of cycloalkenone (6) with FeCl2eMe2Mg (4d)a
O
Me
n
Me
OH
O
0 °C
6
FeCl2
+
Me2Mg
+
n
5 min
THF
n
8
4.2. Reaction of FeCl2eMe2Mg reagent with ketones
1 h
4g
7
The commercially available anhydrous FeCl2 (2.0 mmol) was
charged with 4.0 mL of anhydrous THF, and the mixture was son-
icated for 0.5 h using an ultrasonic cleaner. The obtained suspen-
sion was cooled at 0 ꢁC, and Me2Mg (1.0 mmol) was added. After
the mixture was stirred for 5 min at 0 ꢁC, ketone (1.0 mmol) in THF
(2.0 mL) was added to the mixture. The mixture was stirred at 0 ꢁC,
and quenched with 1 M aqueous HCl.
Entry
FeCl2 (equiv)
Enone (1.0 equiv)
4g (equiv)
7 (%)
8 (%)
1
2
3
4
d
6a (n¼1)
6a (n¼1)
6a (n¼1)
6b (n¼2)
1.5
1.5
1.2
1.2
68 (7a)
nd (7a)
nd (7a)
nd (7b)
13 (8a)
77 (8a)
80 (8a)
62 (8b)
2.0
1.2
1.2
a
Anhydrous FeCl2 (2.0 mmol), organomagnesium (1.5, or 3.0 mmol), and cyclo-
alkenone (6, 1.0 mmol) were used. The preparation of the reagent was performed at
0 ꢁC for 5 min. The yield of the product was determined by 1H NMR after aqueous
work-up using bromoform as an internal standard.
4.2.1. 2-Butyl-1,2,3,4-tetrahydronaphthalen-2-ol (5ab):17 CAS RN
[91671e46e4]. Pale yellow oil. 1H NMR (500 MHz, CDCl3)
d
7.15e7.09 (m, 3H), 7.09e7.04 (m, 1H), 3.00 (ddd, J¼16.5, 9.5,
6.5 Hz, 1H), 2.87 (d, J¼16.5 Hz, 1H), 2.83e2.77 (m, 1H), 2.78 (d,
J¼16.5 Hz, 1H), 1.90e1.83 (m, 1H), 1.79 (ddd, J¼13.0, 9.5, 6.0 Hz, 1H),
1.64e1.53 (m, 2H), 1.50e1.41 (m, 2H, 1H), 1.40e1.31 (m, 2H), 0.94 (t,
3. Conclusion
The 1,2-addition of Grignard reagent to a highly enolizable ketone
prior to enolization is difficult process and has been performed by its
mixture with stoichiometric amount of transition-metal salt. In this
method, a transformation of Grignard reagent into the corresponding
complex reagent should be accomplished efficiently, otherwise
remaining Grignard reagent would induce enolization. To facilitate
the formation of the complex reagent, we proposed a use of R2Mg
instead of RMgX. We thought that a complexation between Grignard
reagent and transition-metal salt proceeds via R2Mg, which is formed
from RMgX through Schlenk equilibrium. Actually, combination of
R2Mg and YbCl3 gave the corresponding complex reagent efficiently,
J¼7.0 Hz, 3H). 13C NMR (CDCl3)
d 135.6, 134.6, 129.7, 128.7, 125.9,
125.8, 70.9, 42.0, 41.2, 33.7, 26.1,25.3,23.3,14.1. The product was
identified with the authentic sample.
4.2.2. 2-Phenyl-1,2,3,4-tetrahydronaphthalen-2-ol (5cd):18 CAS RN
[78318e01e1]. Pale yellow oil. 1H NMR (500 MHz, CDCl3)
d
7.56e7.52 (m, 2H), 7.40e7.35 (m, 2H), 7.32e7.27 (m, 1H), 7.19e7.15
(m, 3H), 7.15e7.10 (m, 1H), 3.35 (d, J¼17.0 Hz, 1H), 3.12 (ddd, J¼16.5,
10.0, 6.0 Hz, 1H), 3.04 (dd, J¼16.5, 1.5 Hz, 1H), 2.80 (dt, J¼17.0,
5.0 Hz, 1H), 2.28 (ddd, J¼13.0, 10.5, 6.0 Hz, 1H), 2.15e2.08 (m, 1H),
1.92 (br s, 1H). 13C NMR (CDCl3)
d 147.6, 135.3, 134.4, 129.4, 128.8,
which performed 1,2-addition to a highly enolizable ketone,
ralone. ItwasalsoshownthattreatmentofMe2MgwithFeCl2 gavethe
reagent, which also added 1,2-manner to -tetralone. The reagent
b-tet-
128.3, 127.1, 126.1, 126.0, 124.8, 72.5, 43.7, 35.4, 26.3. The product
was identified with the authentic sample.
b
could not be prepared efficiently from MeMgI and FeCl2.
Thus, the efficient complexation between diorganomagnesium
and transition-metal salt will easily give us useful complex organ-
ometallic reagents which had difficulty for preparation from
organomagnesium halide.
4.2.3. 2-Vinyl-1,2,3,4-tetrahydronaphthalen-2-ol (5ef):19 CAS RN
[102936e18e5]. Pale yellow oil. 1H NMR (500 MHz, CDCl3)
d
7.15e7.10 (m, 3H), 7.10e7.05 (m, 1H), 6.07 (dd, J¼17.5, 10.5 Hz, 1H),
5.33 (dd, J¼17.5, 1.0 Hz, 1H), 5.12 (dd, J¼10.5, 1.0 Hz, 1H), 3.04e3.00
(m,1H), 3.01 (d, J¼17.0 Hz,1H), 2.87e2.79 (m,1H), 2.84 (d, J¼17.0 Hz,
1H), 1.97e1.84 (m, 2H), 1.58 (s, 1H). 13C NMR (CDCl3)
d 144.1, 135.2,
4. Experimental section
4.1. General
134.0, 129.4, 128.7, 126.0, 125.9, 112.6, 71.2, 41.8, 34.1, 26.1. The
product was identified with the authentic sample.
4.2.4. 2-Methyl-1,2,3,4-tetrahydronaphthalen-2-ol (5g):13 CAS RN
[33223e85e7]. Pale yellow oil. 1H NMR (500 MHz, CDCl3)
Nuclear magnetic resonance spectra were taken on Varian UNITY
INOVA 500 (1H, 500 MHz; 13C, 125.7 MHz) spectrometer using tet-
d
7.14e7.09 (m, 3H), 7.08e7.04 (m, 1H), 3.01 (ddd, J¼16.5, 9.0, 6.5 Hz,
ramethylsilane for 1H NMR as an internal standard (
d
¼0 ppm), CDCl3
1H), 2.88 (d, J¼17.0 Hz, 1H), 2.87e2.79 (m, 1H), 2.82 (d, J¼17.0 Hz,
for 13C NMR as an internal standard (
d
¼77.0 ppm). 1H NMR data are
1H), 1.93e1.86 (m, 1H), 1.84e1.76 (m, 1H), 1.36 (s, 3H). 13C NMR
reported as follows: chemical shift, multiplicity (s¼singlet,
d¼doublet, t¼triplet, q¼quartet, quint¼quintet, sext¼sextet,
sept¼septet, br¼broad, m¼multiplet), coupling constants (Hz), and
integration. Flash column chromatography was carried out using
(CDCl3) d 135.3, 134.8, 123.0, 128.9, 126.2, 126.1, 69.4, 43.8, 36.0, 28.9,
26.6. The product was identified with the authentic sample.
4.2.5. Methyl 10-oxoundecanoate (9):20 CAS RN [18993e09e4].
Kanto Chemical silica gel (spherical, 40e100
mm).
Colorless oil. 1H NMR (500 MHz, CDCl3)
d
3.65 (s, 3H), 2.40 (t, J¼8.0 Hz,