3
1
2
3
4
5
6
7
8
9
We found that dearomatized products 3 can be used as
22 (Scheme 4). Ammonium 6 was successfully dearomatized to
23 give 7 in good yield. As another example, we succeeded in
24 the C3-borylation of ammonium 8 under Phipps’ C–H
25 borylation conditions[5] followed by the dearomative
26 allylation of 9 to give boron-bearing compound 10. Because
27 of the instability of 10, we directly treated the crude 10 with
28 NaBO3. As a result, the reaction proceeded through keto-
29 enol tautomerization (11 and 12), giving C3-
30 hydroxynaphthalene 13 in 22% yield over three steps from 8
31 (average yield in each step is 60%).
a synthetic intermediate for further structural elaboration
(Scheme 3). Oxidation of a crude mixture of 3A using
mCPBA gave C4-allylated benzyl alcohol 4A. For 3I which
has a quaternary carbon at the C4 position, the same
protocol furnished enone 4I in moderate yield.[16] These
examples demonstrate that this dearomative method can be
used for the production of both allylated arenes and alicyclic
systems.
10
Scheme 3. Elaboration of the allylated diene products
32
In summary, we developed a dearomative allylation of
SnnBu3
33 benzyl ammoniums with allylstannane by using a palladium
34 catalyst. With the high C4-selectivity of this methodology as
35 well as the utility of the benzyl amines/ammoniums as a
36 versatile platform in organic synthesis, we believe that the
37 method would find wide use in synthetic chemistry to form
38 multi-substituted cyclic compounds. Further studies to add
39 to the synthetic value of this method are underway in our
40 laboratory.[17]
2
cat. Pd/L1
OH
mCPBA
1A
THF
60 °C
0 °C to RT
H
3A
4A: 34% (2 steps)
SnnBu3
2
cat. Pd/L1
mCPBA
O
41
1I
0 °C to RT
THF
60 °C
42 This work was supported by JSPS KAKENHI Grant
43 Number JP19H02726 (to J.Y.), JP18H04661 (Hybrid
44 Catalysis), JP19K15573, and The SATOMI Scholarship
45 Foundation (to K.M.). The Materials Characterization
46 Central Laboratory in Waseda University is acknowledged
47 for the support of HRMS measurement.
Ar
Ar = 4-tBuC6H4
Ar
3I
4I: 47% (2 steps)
11
12
Sequential transformation of benzyl amines using
13 directed C–H functionalization followed by the present C4-
14 dearomative allylation could provide a novel strategy for the
15 synthesis of multi-substituted arenes as well as alicyclic
48 Supporting
Information
is
available
on
49 http://dx.doi.org/10.1246/cl.******.
50
16
17
Scheme 4. Combination of the present method with C–H
functionalization
51 References and Notes
SnnBu3
1) nBuLi;
EtBr
2 (1.0 equiv)
cat. Pd/L1
H
Et
C8
Et
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
† These authors contributed equally.
I
NMe2
NMe3
1
2
a) F. N. Jones, R. L. Vaulx, C. R. Hauser, F. N. Jones, R. L.
Vaulx, C. R. Hauser, J. Org. Chem. 1963, 28, 3461. b) K. P.
Klein, C. R. Hauser, J. Org. Chem. 1967, 32, 1479. c) V.
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47, 149.
For dimethylamino group-directed meta-C–H arylation, see: a) Z.
Dong, J. Wang, G. Dong, J. Am. Chem. Soc. 2015, 137, 5887.
Other meta-C–H functionalizations of benzyl amines, see: b) P.
Wang, M. E. Farmer, J.-Q.Yu, Angew. Chem., Int. Ed. 2017, 56,
5125. c) Q. Ding, S. Ye, G. Cheng, P. Wang, M. E. Farmer, J.-Q.
Yu, J. Am. Chem. Soc. 2017, 139, 417.
a) H. J. Davis, M. T. Mihai, R. J. Phipps, J. Am. Chem. Soc. 2016,
138, 12759. b) M. T. Mihai, R. J. Phipps, Synlett 2017, 28, 1011.
c) H. J. Davis, G. R. Genov, R. J. Phipps, Angew. Chem., Int. Ed.
2017, 56, 13351. d) b) W. A. Golding, R. Pearce-Higgins, R. J.
Phipps, J. Am. Chem. Soc. 2018, 140, 13570. e) M. T. Mihai, H.
J. Davis, G. R. Genov, R. J. Phipps, ACS Catal. 2018, 8, 3764.
For related meta-selective transformations, see. f) W. A. Golding,
R. Pearce-Higgins, R. J. Phipps, J. Am. Chem. Soc. 2018, 140,
13570. g) W. A. Golding, R. J. Phipps, Chem. Sci. 2020,
Advanced Article (DOI: 10.1039/D0SC00105H). For a relating
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2) MeI
[35%]
THF
60 ºC
H
6
7
5
[88%]
B2(pin)2
OTs
Cl
cat. [Ir(cod)OMe]2.
NMe3
NMe3
SO3
nBu4N
Me
C3
N
N
H
Bpin
3
4
L2
then, brine
8
9
SnnBu3
via
2 (1.0 equiv)
cat. Pd/L1
NaBO3
THF
60 ºC
H
H
Bpin
10
OH
11
5
Me
Me
H
O
OH
13
[22%, 3 steps]
12
18
19 molecules. To demonstrate this, we performed a directed-
20 ortho metalation of naphthylmethyl amine 5 followed by an
21 ammonium formation, producing C8-alkylated compound 6