Catalytic Direct-Type Addition Reactions of Alkylarenes with Imines and Alkenes

Article abstract of DOI:10.1002/anie.201711291

Catalytic addition reactions of very weakly acidic nonactivated alkylarenes such as toluene and its derivatives were developed by using a strongly basic mixed catalyst system under mild reaction conditions. The addition reactions with imines and alkenes proceeded smoothly under proton-transfer conditions to afford the desired products in good to high yields, and high levels of regio- and stereoselectivity were achieved. It was also revealed that the asymmetric addition reaction of an alkylarene was possible.

Full text of DOI:10.1002/anie.201711291

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Accepted Article
Title: Catalytic Direct-type Addition Reactions of Alkylarenes with
Imines and Alkenes
Authors: Yasuhiro Yamashita, Hirotsugu Suzuki, Io Sato, Tsubasa
Hirata, and Shu Kobayashi
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201711291
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10.1002/anie.201711291
Angewandte Chemie International Edition
COMMUNICATION
Catalytic Direct-type Addition Reactions of Alkylarenes with
Imines and Alkenes
Yasuhiro Yamashita, Hirotsugu Suzuki, Io Sato, Tsubasa Hirata, and Shū Kobayashi*
Dedication ((optional))
Abstract: Catalytic addition reactions of very weakly acidic
nonactivated alkylarenes such as toluene and its derivatives were
developed by using a strongly basic mixed-catalyst system under
mild reaction conditions. The addition reactions with imines and
alkenes proceeded smoothly under proton transfer conditions to
afford the desired products in good to high yields, and high levels of
regio- and stereoselectivities were achieved. It was also revealed
that the asymmetric addition reaction of an alkylarene was possible.
of alkylarene as the substrate.[7] Recently, radical C–C bond-
forming reactions at benzylic positions under hydrogen atom
transfer conditions using a photocatalyst have been reported,[8]
although control of stereoselectivity remains difficult in these
systems. Carbene insertion is another strategy used to activate
alkylarenes. While carbene insertions are applied to
stereoselective reactions, diazo compounds are always required
for the preparation of carbene species, and applicable
alkylarenes are limited to electron-rich derivatives.[9] In contrast
to these two methods, catalytic benzyl anion formation through
deprotonation is a simple method that can occur by using a
catalytic amount of strong base species. Pines et al. reported
alkaline-metal-catalyzed reactions of alkylarenes with olefins;
however, yields were not sufficient in most cases because of the
formation of by-products.[10] In a similar strategy, Screttas et al.
reported alkylation reactions of toluene and xylene under a high-
pressure ethylene atmosphere with a mixture of strong base
catalysts.[11] Recently, Takemoto, Matsuzaka, et al. investigated
condensation reactions between alkylarenes and aromatic
aldehydes in the presence of Ru and base catalysts.[12] These
reactions, however, required high temperature to complete the
desired transformation, and control of the reactivity and
selectivity is very difficult under these harsh reaction conditions.
Therefore, it is worth investigating base-catalyzed benzylic
activation of alkylarenes for C–C bond-forming reactions under
milder reaction conditions.[13] Here, we report the development of
Brønsted base-catalyzed addition reactions of nonactivated
alkylarenes, including regio- and stereocontrolled reactions.[14]
Catalytic carbon–carbon (C–C) bond-forming reactions that
proceed through direct functionalization of carbon–hydrogen (C–
H) bonds are a hot research topic in organic chemistry.[1] Among
them, Brønsted base-catalyzed C–C bond-forming reactions are
promising because the reactions proceed under proton transfer
conditions with ideal atom economy.[2] Although a number of
carbon pronucleophiles have been successfully employed in the
reactions, a significant limitation has been the range of available
substrate structures; that is, carbon pronucleophiles bearing
weakly acidic hydrogen atoms (pKa in DMSO >30) are difficult to
employ,[3] and more than one equivalent of strong base is
typically required to promote the desired reactions. On the other
hand, we have recently reported a simple but powerful method
that extends the use of these Brønsted base-catalyzed reactions
of weakly acidic pronucleophiles. By designing strongly basic
reaction intermediates, termed product bases, catalytic
stereoselective addition reactions of simple amides,[4a]
esters,[4b,c] alkylazaarenes,[4d] and so on[4e,f] proceeded smoothly.
However, much more weakly acidic carbon pronucleophiles (pKa
in DMSO >40) such as simple alkylarenes remain very
challenging substrates to activate by using typical Brønsted
base catalyst systems.
Catalytic addition reactions of toluene to N-alkylimines were
designed and conducted in the presence of a catalytic amount of
KOtBu and lithium 2,2,6,6-tetramethylpiperidide (LiTMP),[15]
which system has sufficiently strong basicity to deprotonate the
benzylic hydrogen atom smoothly even at –78 °C, as
investigated by O’Shea et al. (LiNK system).[16] In these
systems, strongly basic metal dialkylamides forms as product
bases.[17] When N-tert-butylimine 1a was used as an electrophile,
the desired reaction proceeded smoothly with 20 mol% of the
base species (Table 1, entry 1). The combined use of LiTMP
and KOtBu was essential for efficient formation of the benzyl
anion; neither LiTMP nor KOtBu alone catalyzed the reaction
(entries 2 and 3). Although the tert-butyl group is normally
removed under very harsh acidic conditions,[18] no deprotection
of the tert-butyl group was observed under various harsh acidic
conditions in our initial trial. Therefore, we investigated other
protected imines, and the N-p-methoxycumylimine 1b was found
to be an appropriate electrophile for the catalytic addition, and
the desired product was obtained in high yield (entry 4). We also
found that the desired reaction proceeded in the presence of
only 5 mol% of LiTMP and KOtBu, with a decreased amount of
toluene (1.2 equiv.), and tert-butyl methyl ether (TBME) was
found to be the best of the ether solvents (entry 7).
Nonactivated alkylarenes such as toluene, ethylbenzene,
and xylenes are commercially available, inexpensive, and easy-
to-handle reagents; indeed, they are commonly used as solvents
in organic synthesis because of their high stability.[5] In the
structures of alkylarenes, sp3 C–H bonds at the benzylic
positions on the side alkyl chains are more reactive than sp2 C–
H bonds on the aromatic ring parts,[6] but acidity of the sp3 C–H
bonds are very weak (pKa in DMSO >40). One general catalytic
method that can be used to form a C–C bond at the benzylic
position is a radical addition reaction through generation of a
benzyl radical; however, the reaction usually requires
a
stoichiometric amount of radical initiator and an excess amount
[a]
Dr. Y. Yamashita, Dr. H. Suzuki, I. Sato, T. Hirata, Prof. Dr. S.
Kobayashi
Department of Chemistry, School of Science, The University of
Tokyo
Hongo, Bunkyo-ku, Tokyo, Japan
E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp
Supporting information for this article is given via a link at the end of
the document. ((Please delete this text if not appropriate))
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10.1002/anie.201711291
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COMMUNICATION
Table 1. Catalytic Addition Reaction of Toluene with Imines [a]
Table 2. Catalytic Addition Reactions of Alkylarenes [a]
KOtBu (x mol%)
LiTMP (y mol%)
KOtBu (5.0 mol%)
LiTMP (5.0 mol%)
N
R
R
NH
+
N
PMP
PMP
Ph
NH
R
+
Solv. (0.5 M),
–78 ºC
R
TBME (0.5 M),
–40 ºC, 18 h
PMP = p-MeOC6H4
Ph
Ph
Ph
1b
0.5 mmol
2
1
2a
1.2 equiv.
3
3
5.0 equiv.
0.5 mmol
Entry
1 [c]
x
y
R
Solv.
THF
Time (h)
12
Yield (%)[b]
Quant.
NR
OMe
PMP
Ph
NH
PMP
NH
PMP
PMP
NH
20
20
0
20
Me
Ph
Ph
OMe
OMe
3bd, 85% yield[b]
3bc, 86% yield[b]
3bb, 90% yield
[c]
2
0
Me
THF
16
tBu
NH
PMP
NH
PMP
Ph
NH
[c]
3
20
5
Me
THF
16
NR
Ph
Ph
F
F
3be, 84% yield
3bg, 83% yield
3bf, 88% yield[c,d]
4
5
6
7
5
PMP
PMP
PMP
PMP
THF
18
85
iPr
Et
Me
5
5
Et2O
CPME
TBME
18
86
PMP
NH
PMP
NH
NH
PMP
Ph
NH
Ph
3bh, 78% yield
Ph
5
5
18
83
3bi, 82% yield[e]
3bj, 78% yield
PMP NH
5
5
18
93 (87)
PMP
Ph
PMP
NH
PMP
Ph
NH
Ph
N
Ph
[a] The reaction of 1 (0.500 mmol) with 2a (0.600 mmol) was carried out in a
solvent (1.0 mL) at –78 oC using KOtBu (0.025 mmol) and LiTMP (0.025
mmol) unless otherwise noted. PMP = p-MeOC6H4. CPME = cyclopentyl
methyl ether. TBME= tert-butyl methyl ether. [b] Determined by 1H NMR
analysis with durene as internal standard. The yield in parentheses was an
isolated yield. [c] ca. 12 equivalents (0.5 mL) of toluene were used in 0.2 M.
Ph
Me
Me
3bn, 90% yield[f]
syn/anti = 98/2
,
3bk, 86% yield
3bl, 73% yield
3bm, 60% yield[c]
[a] The reaction of 1b (0.500 mmol) with 2 (2.50 mmol) was carried out in
TBME (0.5 M) at –40 oC using KOtBu (0.025 mmol) and LiTMP (0.025 mmol)
unless otherwise noted. The yields were determined after isolation. [b]
Alkylarene (1.2 equiv.) was used, and the reaction was conducted at –78 °C.
[c] KOtBu (10 mol%) and LiTMP (10 mol%) were used. [d] The reaction was
conducted at –78 °C. [e] KOtBu (20 mol%) and LiTMP (20 mol%) were used.
[f] CPME was used as a solvent and the reaction was conducted at –78 °C.
Relative configuration of the product shown in the table is defined as syn.
The substrate scope of the reaction with respect to the
alkylarene was examined. The reactions were conducted using
5.0 equiv. of alkylarene at –40 °C as standard conditions due to
lower reactivity of the alkylarenes employed (Table 2).
Alkylarenes bearing an electron-donating methoxy group gave
the desired products 3bb, 3bc, and 3bd in high yields,
irrespective of the position of the methoxy group on the aromatic
ring. The electron-deficient alkylarenes, m- and o-fluorotoluenes,
were also a good substrate for the reaction, and the desired
products 3be and 3bf were obtained in high yields. Bulky alkyl
groups at the para position of the alkylarene did not affect the
reactivity, and 4-tert-butyltoluene 2g reacted with the imine
smoothly to afford the product 3bg. Surprisingly, reactive
benzylic hydrogen atoms on either the isopropyl or ethyl group
persisted under the strongly basic reaction conditions, and only
hydrogen atoms at the methyl groups were activated by the
mixed-base catalyst system to afford the products 3bh and 3bi.
This selectivity toward primary alkyl groups differed from typical
cases of carbene insertion reactions, and the mixed strong base
catalyst system achieved complete mono-adduct selectivity
without using any complex ligands.[9a,e,g] Furthermore, when
xylenes were used as nucleophiles, the desired mono-adducts
3bj, 3bk, and 3bl were obtained in high yields. 3-Methylpyridine
was also applicable for this reaction, and the product 3bm was
obtained in moderate yield. Finally, a catalytic reaction with
ethylbenzene was investigated. Gratifyingly, after optimization of
the reaction conditions, the catalyst system was found to control
syn/anti selectivity without the addition of any ligands, and a
highly diastereoselective reaction proceeded to give 3bn.
the desired product 3ga in good yield. The reactions using alkyl-
substituted imines on the benzene ring proceeded smoothly to
afford the desired products 3ha and 3ia. When substrate 1i, with
a relatively acidic hydrogen atom at the benzylic position, was
used, the desired product 3ia was obtained in good yield without
any by-product formation. The 2-naphthyl group did not affect
the reaction, and the desired product 3ja was formed effectively.
Pyridine-containing imines, with either 4- or 2-pyridyl groups,
showed high reactivity without any side reactions such as
deprotonation of the sp2 hydrogen atoms on the pyridine rings to
provide the products 3ka and 3la. The quinolyl-containing imine
also reacted smoothly to afford the product 3ma. We also
investigated catalytic reactions of ethylbenzene with several
imines. Moderate to good yields and high diastereoselectivities
were obtained for the formation of 3cl–3il. We could
successfully demonstrate the catalytic addition reactions of
many nonactivated alkylarenes with the imines by using the
KOtBu and LiTMP mixed-catalyst system.
The p-methoxycumyl group was removed under acidic
conditions. After treatment with TFA at 50 °C, the desired
primary amines were obtained (Scheme 1). In addition, the
diastereomer ratio of the product from ethylbenzene did not
change during the deprotection step. The product 4ba is a
precursor of biologically active opioid agonists.[19] Other
derivatives are also accessible by using this methodology.
The scope of the reaction with respect to the imines was
then investigated under the same conditions (Table 3). Although
an imine bearing a methoxy group at the para position showed
lower reactivity, methoxy groups at meta and ortho positions did
not affect the reactivity, and the desired products 3ca, 3da, and
3ea were afforded in good yields. Another electron-donating
group, the dimethylamino group, also affected the reactivity
slightly, giving the desired adduct 3fa in moderate yield. On the
other hand, electron-deficient fluorine-containing imine 1g gave
We then examined catalytic addition reactions of alkylarenes
with phenyl substituted alkenes (Table 4).[20] In these reactions,
strongly basic benzylic carbanions form as product bases. It was
found that the catalytic addition reaction of toluene with stilbene
proceeded smoothly in the presence of KOtBu, LiTMP, and
N,N,N¢,N¢¢,N¢¢-pentamethyldiethylenetriamine (PMDTA)[21] to
afford the desired adduct 6aa in high yield. PMDTA might
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COMMUNICATION
Table 3. Catalytic Addition Reaction of Toluene with Imines [a]
Table 4. Catalytic Addition Reactions with Stilbene Derivatives
KOtBu (x mol%)
LiTMP (x mol%)
PMDTA (2x mol%)
KOtBu (5.0 mol%)
LiTMP (5.0 mol%)
R1
R1
R2
N
PMP
PMP
NH
+
R
TBME (0.5 M),
–40 ºC, 18 h
PMP = p-MeOC6H4
Ph
+
Ar
Ar
CPME (0.5 M), 24 h
R2
2a (R=H)
2l (R=Me)
5.0 equiv.
1
R
5
0.6 mmol
6
2a
3
Me N
2
N
NMe2
0.5 mmol
PMDTA:
Me
Ph
Ph
Ph
(p-MeO)C6H4
(p-MeO)C6H4
(p-MeO)C6H4
PMP
NH
PMP
NH
PMP
NH
PMP
NH
Ph
Ph
Ph
MeO
Ph
x = 5, 2a = 2.0 equiv.,
at 0 o
6aa, 97% yield
x = 10, 2a = solvent,
at 60 o
6ba, quant. yield
Me2N
x = 10, 2a = 4.0 equiv.,
at 0 o
MeO
3ca, 46% yield
OMe
C
C
C
3da, 85% yield
PMP NH
3ea, 89% yield
3fa, 64% yield
6ca, 93% yield
Ph
PMP
NH
PMP
NH
Ph
PMP
NH
x = 20, 2a = solvent,
x = 20, 2a = solvent,
at 40 oC for 18 h
6ea, 34% yield
at 40 oC for 18 h
Ph
Ph
Ph
Ph
Ph
6da, 72% yield
tBu
3ha, 79% yield
F
iPr
mixing KOtBu and LiTMP; M-TMP was considered to be the
active catalyst species in the reactions. M-TMP then
deprotonates a benzylic hydrogen from the alkylarene to form a
benzylic carbanion species. The latter attacks the C=N or C=C
double bond to generate a strongly basic reaction intermediate
(product base). After the formation of the strongly basic product
base, two reaction pathways can be considered. One is direct
deprotonation of the next alkylarene by the reaction intermediate
to regenerate benzylic carbanion species (Path A). The second
path involves regeneration of the M-TMP species through
deprotonation of H-TMP by the intermediate (Path B). The actual
catalytic pathway is unclear at this stage and is under
investigation.
3ja, 88% yield
PMP NH
3ga, 75% yield
3ia, 81% yield
PMP
NH
PMP
NH
PMP NH
Ph
Ph
N
Ph
N
N
MeO
3cl, 58% yield[b,c]
syn/anti = 95/5
,
3ka, quant. yield
3la, 97% yield
3ma, 69% yield[d]
PMP
NH
PMP
NH
PMP
NH
PMP
NH
Ph
Ph
,
Ph
MeO
Ph
Me2N
tBu
iPr
3il, 71% yield[b,d]
syn/anti = 90/10
3hl, 65% yield[c]
syn/anti = 96/4
,
3fl, 49% yield[d,e]
syn/anti = 93/7
,
3dl, 74% yield[b,d]
syn/anti = 90/10
,
[a] The reaction of 1 (0.500 mmol) with 2a or 2l (2.50 mmol) was carried out in
TBME (0.5 M) at –40 oC for 18 h using KOtBu (0.025 mmol) and LiTMP (0.025
mmol) unless otherwise noted. The yields were determined after isolation. [b]
The reaction was carried out at –60 °C. [c] CPME was used as a solvent. [d]
KOtBu (10 mol%) and LiTMP (10 mol%) were used. [e] A mixed-solvent
system (ethylbenzene/THF = 9:1) was used. The reaction concentration was
0.25 M.
H
N
R3
R3
(H-TMP)
R2
M
X
H
R1
1 or 5
X = N or CH
R4
2-I
2
R4
NH2
PMP
NH
M
LiTMP
Ph
TFA, 50 ºC,
12.5 h
Ph
3 or 6
Ph
+ KOtBu
(+ Ligand)
N
Ph
3ba
4ba
M = K/Li
Path B
88% yield
(+Ligand)
NH2
(M-TMP)
PMP
Ph
NH
2
Ph
Ph
Ph
TFA, 50 ºC,
3 h
Path A
R3
R3
R2
X
R2
4bl
H-TMP
3bl
syn/anti = 98/2
XH
M
68% yield, syn/anti = 98/2
R1
R1
R4
R4
3 or 6
Scheme 1. Deprotection of the p-methoxycumyl group under acidic conditions
3-I or 6-I
Figure 1. Proposed catalytic cycle for the addition reactions of alkylarenes
activate the benzylic carbanion species as
a ligand by
coordination to the metal atoms to deaggregate their higher
aggregation state, thereby facilitating the reaction with stilbene,
which has lower electrophilicity compared with imines. We then
examined the substrate scope of the catalytic addition reactions
with the alkenes. The reactivity of electron-rich stilbene 5b was
slightly decreased, and heating conditions were required for
good conversion to afford 6ba. Surprisingly, nonsymmetric
stilbene derivative 5c gave the desired adduct 6ca with
complete regioselectivity, which indicated that the electronic
properties of the stilbene derivatives could be used to control the
electrophilicity. b-Alkylstyrenes were also found to be suitable
electrophiles, and the desired products 6da and 6ea were
obtained in moderate to good yields.
A preliminary trial of an asymmetric variant of the reaction of
toluene with an imine was shown in Scheme 2. By using a chiral
potassium complex prepared from (trimethylsilyl)methyl-
potassium (KCH2SiMe3)[22] and chiral diamine L,[23] the addition
reaction of toluene with 1b proceeded in high yield with
significant enantioselectivity (Scheme 2). To the best of our
knowledge, this is the first example of a catalytic asymmetric
addition reaction of an alkylarene with an imine.
In summary, we have developed catalytic addition reactions
of very weakly acidic nonactivated alkylarenes by using a
strongly basic mixed-catalyst system under mild reaction
conditions. The reactions with imines and phenyl substituted
alkenes proceed smoothly under proton transfer conditions to
afford the desired products in good to high yields, and high
We postulate a plausible catalytic cycle for the addition
reactions, as shown in Figure 1. First, a strong mixed-base
system, M-TMP (M = K/Li, K and Li mixture) was formed by
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10.1002/anie.201711291
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COMMUNICATION
McCann, D. Wang, P. Chen, S. S. Shahl, G. Liu, Science 2016, 353,
1014–1018.
levels of regio- and stereoselectivities are achieved. The key
step in this catalytic process is the formation of dialkylamides or
[8]
[9]
a) M. Mella, M. Fagnoni, A. Albini, Eur. J. Org. Chem. 1999, 2137-2142;
b) F. Fagnoni, D. Dondi, D. Ravelli, A. Albini, Chem. Rev. 2007, 107,
2725-2756
KCH2SiMe3 (10 mol%)
L (11 mol%)
N
PMP
PMP
Ph
NH
+
–78 oC, 18 h
Ph
a) H. M. L. Davies, Q. Jin, P. Ren, Y. Kovalevsky, J. Org. Chem. 2002,
67, 4165–4169. b) M. E. Morilla, M. M. Díaz-Requejo, T. R. Belderrain,
M. C. Nicasio, S. Trofimenko, P. J. Pérez, Organometallics 2004, 23,
293–295; c) L. Goldoni, G. Cravotto, A. Penoni, S. Tollari, G.
Palmisano, Synlett 2005, 6, 927–930; d) H. M. Mbuvi, K. L. Woo,
Organometallics 2008, 27, 637–645; e) H.-Y. Thu, G. S.-M. Tong, J.-S.
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Am. Chem. Soc. 2014, 136, 9792–9796.
Ph
1b
2a
3ba
(solv.)
L :
85% yield
56% ee
N
NHMe
Scheme 2. Catalytic asymmetric addition reaction of toluene with 1b
weakly stabilized carbanions as very strongly basic reaction
intermediates; the design of these intermediates allows the
catalytic reactions to proceed with very weakly acidic
pronucleophiles (pKa in DMSO >40). It was also revealed that
an asymmetric addition reaction of an alkylarene proceeded
smoothly. This methodology thus could be a new approach into
catalytic functionalization of the inert C–H bonds of less reactive
substrates. Further studies on the catalyst system are under way
in our laboratory.
[10] a) H. Pines, J. A. Vesely, V. N. Ipatieff, J. Am. Chem. Soc. 1955, 77,
554-559; b) H. Pines, Acc. Chem. Res. 1974, 7, 155-162.
[11] B. R. Steele, C. G. Screttas, J. Am. Chem. Soc. 2000, 122, 2391–2392.
[12] S. Takemoto, E. Shibata, M. Nakajima, Y. Yumoto, M. Shimamoto, H.
Matsuzaka, J. Am. Chem. Soc. 2016, 138, 14836–14839.
[13] Catalytic addition reactions of alkylarenes bearing directing
functionalities, see a) J. Oyamada, Z. Hou, Angew. Chem. Int. Ed. 2012,
51, 12828-12832; related works, see b) B.-T. Guan, B. Wang, M.
Nishiura, Z. Hou, Angew. Chem. Int. Ed. 2013, 52, 4418-4421; c) Y.
Luo, H. Teng, M. Nishiura, Z. Hou, Angew. Chem. Int. Ed. 2017, 56,
9207-9210; d) M. Nishiura, F. Guo, Z. Hou, Acc. Chem. Res. 2015, 48,
2209-2220; Catalytic direct-type allylation reactions of imines via
benzylic C–H bond deprotonation has been reported recently. See e)
W. Bao, H. Kossen, U. Schneider, J. Am. Chem. Soc. 2017, 139, 4362-
4365.
Acknowledgements
This work was partially supported by a Grant-in-Aid for Science
Research from the Japan Society for the Promotion of Science
(JSPS) and Ministry of Education, Culture, Sports, Science and
Technology (MEXT), and the Japan Science and Technology
Agency (JST). H.S., I.S. and T.H. thank MERIT program, The
University of Tokyo for financial support. H.S. and I.S. also
thank JSPS Research Fellowships for Young Scientists for
financial support.
[14] During the submission process of this manuscript, Guan et al. reported
potassium base-catalyzed additions of alkylpyridines or diarylmethane
to styrenes. a) D.-D. Zhai, X.-Y. Zhang, Y.-F. Liu, L. Zheng, B.-T. Guan,
Angew. Chem. Int. Ed. 2018, 57, 1650-1653; b) Y.-F. Liu, D.-D. Zhai,
X.-Y. Zhang, B.-T. Guan, Angew. Chem. Int. Ed. Early view.
[15]
S. Kobayashi, Y. Mori, J. S. Fossey, M. M. Salter, Chem. Rev. 2011,
111, 2626–2704.
[16] a) P.Fleming, D. F. O’Shea, J. Am. Chem. Soc. 2011, 133, 1698–1701;
b) M. Blangetti, P. Fleming, D. F. O’Shea, J. Org. Chem. 2012, 77,
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Keywords: strong base • catalysis • alkylarene • addition
reaction • stereoselective
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10.1002/anie.201711291
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
Y. Yamashita, H. Suzuki, I. Sato, T.
Hirata, S. Kobayashi*
KOtBu (cat.)
LiTMP (cat.)
XH
X
R4
R4
R3
R3 = H, Me
+
R1
R1
R3
HIgh yields
High diastereoselectivities
Page No. – Page No.
X= N–C(CH3)2PMP
or CH–R2
Catalytic Direct-type Addition
Reactions of Alkylarenes with Imines
and Alkenes
Catalytic addition reactions of very weakly acidic nonactivated alkylarenes such as
toluene and its derivatives were developed by using a strongly basic mixed-catalyst
system under mild reaction conditions. The addition reactions with imines and
alkenes proceeded smoothly under proton transfer conditions to afford the desired
products in good to high yields. It was also revealed that the asymmetric addition
reaction of an alkylarene was possible.
This article is protected by copyright. All rights reserved.