Organic Letters
Letter
transformed thermodynamic 1,4-product was obtained when
Table 1. Hydroboration of Pyridine Catalyzed by 1−3
2
,10
the reaction was heated.
Thus, for magnesium based
complexes, accelerating the kinetic 1,2-selective reaction and
preventing the thermodynamic 1,4-reaction/transformation,
become the key issue for obtaining high 1,2-dihydropyridine
product.
Herein, we developed magnesium complexes ligated by
phosphinimino amides (Scheme 1). Complexes 1 (R = Cy
a
b
entry
cat
T (°C)
time (h)
yield (%)
(2a:2a′)
1
1
2
3
1
1
1
1
2
2
25
40
70
25
25
70
70
10
1
99.5
98.3
99.2
71.4
99.0
99.1
64.0
>20:1
>20:1
>20:1
1.3:1
>20:1
>20:1
1.9:1
Scheme 1. Structures of Phosphinimino-amido Magnesium
0.2
30
10
0.2
20
c
4
5
6
7
d
3
a
Reaction conditions: pyridine (0.20 mmol), HBpin (0.20 mmol),
C D as solvent (0.50 mL). Catalyst loading is 2 mol % relative to
6
6
b
1
pyridine. Yields and 2a:2a′ ratio were determined by H NMR
spectroscopy using methyltriphenylsilane as an internal standard.
c
d
C D O (d -THF) as a solvent. 3 is magnesium hydride complex
4
8
8
12c
ligated with β-diketiminate skeleton.
based catalysts to reach high 1,2-regioselective dearomatization
of pyridine, especially in a wide temperature scope.
The following investigations on various pyridine reagents
were then carried out with 1, and the collected data are listed
in Scheme 2 and Table S2. Under mild conditions, para-
substituted pyridines were exclusively transformed to 1,2-
products (2b, 2c). For pyridines with meta-substituents like
methyl, methoxyl, and halogens, the 1,2-selective products N-
boryl-3-substituted-1,2-dihydropyridines (2d−2j) were pre-
dominant regardless of the substituent type. The electron-
withdrawing group accelerated the reaction, as the adjacent
carbon was easily attacked by a nucleophilic species.
Contrarily, the electron-donating group retarded the reaction
since it made the reduction of the adjacent carbon very
difficult. Thus, the TOF value for the dearomatization of the
pyridines varied with the electronics of the meta-substituent,
following the trend of I > Br > Cl > F > Ph> Me > OMe
(Table S2). On the other hand, the different trend of them on
1,2-selectivity was presumably due to steric encumbrance.
Much stronger electron withdrawing nitro and cyano groups
led to some side-reaction with the catalyst instead of the
(
cyclohexyl)) was previously reported by our group and
11
1
complex 2 (R = Ph) was synthesized with similar method.
Dinuclear complexes 1 and 2 bridging by two hydrides were
defined by NMR spectrum analyses and characterized with X-
ray diffraction analyses (For the crystal structures of complexes
1
and 2: hydrogen atoms (except the Mg−H) are omitted for
clarity. Thermal ellipsoids are drawn at the 20% probability
level).
At room temperature, 1 was relatively inert to HBpin but
quickly reacted with pyridine to yield complex 4 containing
two pyridine moieties: one is 1,2-reduced pyridine via Mg−H
12
4c
regular hydroboration reaction. When using 2-methyl-
After mixing HBpin, pyridine, and catalyst 1 together, no
pyridine, 2,2-bipyridyl, and 2-methyl-quinoline as the reagents,
no dearomatization took place even at elevated temperatures,
as the ortho-block in pyridines significantly impedes the
S67). The catalytic reaction proceeded smoothly to reach
complete conversion within 10 h at a ratio of N-Bpin-1,2-
dihydropyridine (2a)/N-Bpin-1,4-dihydropyridine (2a′) >
4
,5
dearomatization process. The mostly active reactions were
−
1
found for quinolines and isoquinolines (TOF > 1500 h ), and
the 1,2-selective products of 2k and 2l were exclusively
isolated, which might be attributed to the less aromatic
stabilization of them. Thus, even with a methyl substituent
such as 3-methyl-quinoline, 3-methyl-isoquinoline, and even 1-
methyl-isoquinoline, the reactions proceeded smoothly to give
pure 1,2-regioselective products 2m, 2n, and 2o. With regard
to the N-heterocylcles like pyrazine, pyrimidine, 2,5-dimethyl-
pyrazine, and quinoxaline, 2 equiv of HBpin was required to
produce the doubly hydroborated products 2p, 2q, 2r, and 2s
in good yields.
2
0:1. To our delight, the TOF enhanced correspondingly
−
1
−1
from 12.1 h to 134.5 h when the reaction temperature
remained unchanged (Table 1, entries 1−3 and Table S2).
Complex 2 bearing the ligand with R1 = Ph displayed
analogous catalytic activity and 1,2-regioselectivity at either
room temperature or high temperature (Table 1, entries 5 and
6
2
). On the other hand, a polar solvent like THF decreases the
a:2a’ ratio down to 1.3:1, which should be derived from the
competitive coordination of THF (Table 1, entry 4). On the
other hand, β-diketiminate skeleton ligated magnesium hydride
complex 3 was inert to the reaction at room temperature but
afforded a mixture at high temperature (Table 1, entry 7).
To our knowledge, complexes 1 and 2 are the first magnesium-
The extremely high activity and excellent chemoselective
reduction on the carbonyl substituent rather than the pyridine
ring were realized when using the carbonyl substituted
pyridines (Scheme 3). For example, quantitative conversion
of 2-acetyl-pyridine to 2t was finished in less than 2 min with 1
1
,2
B
Org. Lett. XXXX, XXX, XXX−XXX