.
Angewandte
Communications
our ongoing interest in earth abundant manganese catalyzed
complementary to traditional Friedel–Crafts reactions, which
usually give 3-indolyl alcohols.[13]
The scope with respect to the aldehyde was further tested
(Scheme 3). In sharp contrast to the rhodium-catalyzed
[10,11]
À
C H activation,
herein we disclose a manganese-cata-
À
lyzed C H nucleophilic addition to aldehydes and nitriles by
À
a strategy of dual activation, namely, merging C H activation
by a transition-metal catalyst and aldehyde/nitrile activation
by a Lewis acid (Scheme 1c). Importantly, this protocol is
À
suitable for both aromatic and olefinic C H bonds, and is
applicable to a wide range of aldehydes and nitriles.
At the outset, 2-phenylpyridine (1a) and benzaldehyde
(2a) were selected as model substrates. After an extensive
survey of reaction parameters, it was found that the synergetic
use of dimethylzinc (Me2Zn) and zinc bromide (ZnBr2) was
essential for accessing the expected product 3aa with high
efficiency (Scheme 2).[12] Finally, 3aa was obtained in 81%
Scheme 3. Scope with respect to the aldehyde. Reaction conditions: 1a
(0.5 mmol), 2 (1.0 mmol), [MnBr(CO)5] (0.025 mmol), Me2Zn
(0.75 mmol), ZnBr2 (0.5 mmol), DCE (5 mL), 608C, 12 h. Yields are
those of the isolated products. [a] 1008C. [b] Single isomer.
[c] 10 mol% [MnBr(CO)5]. TIPS=triisopropylsilyl, Ts =4-toluenesul-
fonyl.
protocols,[8] the present reaction was suitable for not only
electron-deficient aldehydes but also electron-neutral and
electron-rich ones (3ab–aj). Different substitution patterns of
aldehydes had no obvious influence on the reaction outcome
(3ak–al). The sterically demanding 1-naphthaldehyde and
various heteroaromatic aldehydes bearing indole, furan, and
thiophene rings were all compatible with this reaction (3am–
ap). Remarkably, a,b-unsaturated cinnamaldehyde gave only
the 1,2-addition product 3aq, without any of the 1,4-addition
product. The more challenging aliphatic aldehydes were next
explored. It turned out that a variety of primary, secondary,
and even tertiary aliphatic aldehydes, both acyclic and cyclic,
were amenable to this protocol at increased temperature
(3ar–ax). Importantly, functionalities such as an olefin, alkyl
bromide, and silylether were well tolerated (3ay–aA).
Scheme 2. Scope with respect to the arene. Reaction conditions:
1 (0.5 mmol), 2a (1.0 mmol), [MnBr(CO)5] (0.025 mmol), Me2Zn
(0.75 mmol), ZnBr2 (0.5 mmol), DCE (5 mL), 608C, 12 h. Yields are
those of the isolated products. [a] Major regioisomer was shown, 3na/
3na’=12:1. [b] 1008C. [c] 10 mol% [MnBr(CO)5]. DCE=1,2-dichloro-
ethane.
yield upon isolation by using mild reaction conditions.
Importantly, the double-addition product 4aa was not
detected during the entire optimization process. Also, the
evolution of methane (CH4) was confirmed by GC analysis.
We then investigated the scope with respect to the arene. A
wide range of functional groups (OMe, NMe2, CO2Et, CF3, F,
Cl, I, etc.) was well tolerated at different positions of the 2-
Next, we pursued the possibility of direct nucleophilic
À
À
arylpyridines (3ba–ma). When two C H bonds were avail-
addition of olefinic C H bonds to aldehydes (Scheme 4).
À
able on the benzene moiety, the C H addition occurred at the
Gratifyingly, the expected product 6a was obtained as the sole
Z stereoisomer from 2-vinylpyridine and 2a. Again, aromatic,
heteroaromatic, and aliphatic aldehydes were all amenable to
this reaction (6b–e). The configuration of 6c was unambig-
uously confirmed by single-crystal X-ray diffraction analy-
sis.[12] 1,1-Disubstituted olefins could also deliver the corre-
sponding products smoothly with perfect stereoselectivity
(6 f–h). The E-configured 1,2-disubstituted olefin containing
sterically more accessible site with high regioselectivity (3na).
1-Pyridylnaphthalene and benzo[h]quinoline were also suit-
able substrates, thus giving the corresponding products
smoothly (3oa,pa). Arenes containing other directing
groups such as pyrimidine, pyrazole, and oxazoline also
worked well (3qa–sa). Heteroarenes bearing thiophene and
indole skeletons successfully delivered the corresponding
products 3ta and 3ua. Of note, the formation of 3ua is
À
a C H bond cis to the pyridine group was a suitable substrate,
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 13659 –13663