Angewandte
Chemie
increase of impurities. 1H NMR (400 MHz, [D5]py,
258C): d = 8.71 (m, 8H, o-CHpy), 7.55 (m, 4H, p-
CHpy), 7.19 (m, 8H, m-CHpy), 6.50 (d, 3J(H,H) =
6.5 Hz, 4H, o-CHDHP), 6.22 (m, 2H, CHallyl), 5.18 (d,
3J(H,H) = 17.5 Hz, 2H, CH2trans,allyl), 5.13 (d, 3J-
(H,H) = 10.3 Hz, 2H,
=
CH2cis,allyl), 4.34 (dd, 3J-
=
(H,H) = 2.3, 6.5 Hz, 4H, m-CHDHP), 4.02 (br, 2H, p-
CH), 2.48 ppm (t, 3J(H,H) = 6.5 Hz, 4H, -CH2-allyl).
13C{1H} NMR (100 MHz, [D5]py, 258C): d = 149.9 (o-
CHpy), 141.7 (o-CHDHP), 138.6 (CHallyl), 135.5 (p-
CH ), 123.5 (m-CH ), 112.3–110.8 ( CH2allyl), 90.1–
95.1 (m-CHDHP), 55.8 (-CH2-allyl), 42–36 ppm (p-
CHDHP). 1H NMR (400 MHz, [D8]THF, 258C): d =
8.56 (m, 8H, o-CHpy), 7.66 (tt, 3J(H,H) = 7.7 Hz,
4J(H,H) = 1.8 Hz, 4H, p-CHpy), 7.26 (m, 8H, m-
py
py
=
CHpy), 6.09–6.17 (br, 4H, o-CHDHP), 5.84 (br, 2H,
3
CHallyl), 4.89 (d, J(H,H) = 10.1 Hz, 2H, CH2trans,allyl),
=
3
4.87 (d, J(H,H) = 7.0 Hz, 2H, CH2cis,allyl), 3.82–3.97
=
(br, 4H, m-CHDHP), 3.39 (br, 2H, p-CHDHP), 2.04 ppm
(br, 4H, -CH2-allyl). 13C{1H} NMR (100 MHz, [D8]THF,
258C): d = 150.8 (o-CHpy), 136.2 (p-CHpy), 124.3 (m-
CHpy), 140.2 (o-CHDHP), 138.7 (CHallyl), 114.4/113.5 (
=
CH2allyl), 98.4/94.8 (m-CHDHP), 50.7/49.7 (-CH2-allyl),
36.9/36.1 ppm (p-CHDHP).
9ins·(9)4: a) 1 (63 mg, 0.52 mmol) was dissolved in
3,5-dimethylpyridine (1.0 mL). Upon cooling, red
crystals suitable for X-ray diffraction were formed
(185 mg, 0.24 mmol, 47%).[12] 1H NMR (400 MHz,
[D8]THF, 258C): d = 8.18 (m, 8H, o-CH9), 7.30 (m, 4,
p-CH9), 6.10 (s, 4H, o-CHDHP), 5.99 (m, 2H, CHallyl),
Scheme 3. Reactions of 1 with methylated pyridine derivatives.
4.73–4.97 (m, 4H, CH2allyl), 3.33 (t, 3J(H,H) = 3.8 Hz,
=
2H, p-CHDHP), 2.24 (br, 28H, CH3 , -CH2-allyl),
9
1.50 ppm (br, 12H, CH3DHP). 13C{1H} NMR (100 MHz, [D8]THF,
several days. 9ins was crystallized as an octahedrally coordi-
nated 3,5-lutidine adduct 9ins·(9)4.[12]
258C): d = 148.32 (o-CH9), 140.44 (CHallyl), 137.36 (p-CH9), 136.06 (o-
CHDHP), 133.01 (m-C ), 113.64 ( CH2allyl), 100.28 (m-CDHP), 46.32
9
=
When 4-tert-butylpyridine (10) was reacted with 1 in
[D8]THF, the ortho-metalation product bis(4-tert-butylpyri-
din-2-yl)calcium (10act) was formed quantitatively within
four days. This observation is ascribed to steric shielding of
the 4-position, thus blocking the 1,3-rearrangement. These
findings indicate an equilibrium between the reactants, the
allylated products, and also the metalated complex 10act.
Whereas the insertion products are formed under kinetic
control, the 4-tert-butyl substituent shifts the equilibrium
toward the thermodynamically favored ortho-metalation
product.
(-CH2-allyl), 37.90 (p-CHDHP), 20.64 (CH3DHP), 18.19 ppm (CH3 ).
9
For further experimental details, NMR data of compounds 5ins,
7ins, 8ins, 10ins, 5act–7act, 10act, kinetic data, and computational
details, see the Supporting Information.
Received: June 17, 2010
Published online: September 10, 2010
À
À
Keywords: allyl ligands · C C coupling · C H activation ·
calcium · density functional calculations
.
In conclusion, insertion of pyridine into the polar allyl
calcium bond gave 1,4-dihydropyridine derivatives regiose-
lectively. The presence of methyl groups on the pyridine ring
resulted in 1,4-addition under kinetic control, followed by
b) S. Visentin, B. Rolando, A. D. Di Stilo, R. Fruttero, M.
Novara, E. Carbone, C. Roussel, N. Vanthuyne, A. Gasco,
J. Med. Chem. 2004, 47, 2688 – 2693; c) M. Litvic, I. Cepanec, M.
Filipan, K. Kos, A. Bartolincic, V. Druskovic, M. M. Tibi, V.
À
C H bond activation of the methyl group. Organocalcium
reagents[16] evidently display an unprecedented reactivity
pattern with respect to the balance between nucleophilicity
and basicity.
Experimental Section
[3] a) B. Das, K. Suneel, K. Venkateswarlu, B. Ravikanth, Chem.
2·(py)4: a) Bis(allyl)calcium (1, 63 mg, 0.52 mmol) was dissolved in
pyridine (1.0 mL). Upon cooling, red crystals suitable for X-ray
diffraction were formed (138 mg, 0.23 mmol, 45%).[12] b) 1 (40 mg,
0.33 mmol) was dissolved in THF (0.8 mL), and a solution of pyridine
(155 mg, 196 mmol) in THF (0.2 mL) was added and stirred for
30 min. Removal of all volatiles resulted in a dark-red powder 2·(py)4
(188 mg, 32 mmol, 95%). Further drying in vacuo resulted in the loss
of pyridine ligands, a viscous product 2·(py)n (n = 1–1.5), and an
Angew. Chem. Int. Ed. 2010, 49, 7795 –7798
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7797