3
1
2
Table 3. The reaction of various tertiary xanthates 1a with electron
deficient alkenes.
22 complex natural product is currently underway in our
2
2
2
3
4
5
laboratory.
EWG
This work was supported by JSPS KAKENHI Grant
Numbers JP16H01156 in Middle Molecular Strategy and
S
R4
EWG
R4
26
2
(5 equiv)
O
SMe
27 JP16H03292, and JST value program Grant Number
28 VP29117941288. K.N. is grateful to the Yamada
29 Foundation, the Kurata Foundation, and the Uehara
30 Memorial Foundation for support through a Research Fund.
AIBN (40 mol%)
R3
R1
n
R3
R1
Bu SnH (2.0 equiv)
3
R2
R2
xylene (0.02 M), MW
180 °C, 5 min.
1
3
3
3
3
34
3
3
1
2
3
We acknowledge Tokushima University for the financial
support of the Research Clusters program of Tokushima
University (No.1802001).
Substrate
Alkene
Product
Yielda
68%
SMe
SO2Ph
O
O
O
O
O
5
6
Supporting
Information
is
available
on
S
2e
http://dx.doi.org/10.1246/cl.******.
Me
Me
3
7 References and Notes
1
1
b
b
4b
3
3
4
4
42
43
8
9
0
1
1
For recent reviews on radical conjugate addition, see a) J. Streuff,
A. Gansäuer, Angew. Chem. Int. Ed. 2015, 54, 14232. b) G. S. C.
Srikanth, S. L. Castle, Tetrahedron, 2005, 61, 10377. c) W.
Zhang, Tetrahedron, 2001, 57, 7237-7262. d) P. M. Sibi, M. Liu,
Enantiomer, 1999, 4, 575-590.
CN
O
O
2g
59%
Me
2
For selected examples, a) S. P. Pitre, N. A. Weires, L. E.
Overman, J. Am. Chem. Soc. 2019, ASAP. b) G. J. Choi, Q. Zhu,
D. C. Miller, C. J. Gu, R. R. Knowles, Nature, 2016, 539, 268. c)
J. C. Lo, Y. Yabe, P. S. Baran, J. Am. Chem. Soc. 2014, 136,
1304. d) M. J. Schnermann, L. E. Overman, Angew, Chem, Int.
Ed. 2012, 51, 9576. e) G. A. Russell, B. Z. Shi, W. Jiang, S. Hu,
B. H. Kim, W. Baik, J. Am. Chem. Soc. 1995, 117, 3952.
Selected recent examples of tertiary carbon radical reactions
from bridgehead tertiary halide, see a) I. Ryu, S. Uehara, H.
Hirao, T. Fukuyama, Org. Lett. 2008, 10, 1005. b) A. Studer, S.
Amrein, F. Schleth, T. Schulte, J. C. Walton, J. Am. Chem. Soc.
2003, 125, 5276. c) D. O. Jang, D. H. Cho, C.-M. Chung, Synlett,
2001, 1923. d) K. Olofsson, S.-Y. Kim, M. Larhed, D. P. Curran,
A. Hallberg, J. Org. Chem. 1999, 64, 4539. e) G. A. Kraus, T. M.
Siclovan, B. Watoson, Synlett, 1995, 201. F) M. Ohno, K.
Ishizaki, S. Eguchi, J. Org. Chem. 1988, 53, 1285.
4
4
4
4
4
4
5
6
7
8
4
g
SMe
49
SO2Ph
O
5
0
3
2
e
90%
S
51
Me
Me
5
5
5
5
5
2
3
4
5
6
1
c
4c
S
CO2Ph
57
5
8
O
SMe
2
b
63%
5
9
4
Selected recent examples of tertiary carbon radical reactions
from tertiary halides other than bridgehead halide, see a) X. Wu,
W. Hao, K.-Y. Ye, B. Jiang, G. Pombar, Z. Song, S. Lin, J. Am.
Chem. Soc. 2018, 140, 14836. b) A. García-Domínguez, Z, Li, C.
Nevado, J. Am. Chem. Soc. 2017, 139, 6835. C) J. Guiard, Y.
Rahali, J.-P. Praly, Eur. J. Org. Chem. 2014, 4461. D) M. Ueda,
H. Miyabe, A. Nishimura, O. Miyata, Y. Takemoto, T. Naito,
Org. Lett. 2003, 5, 3835.
a) S. C. Dolan, J. MacMillan, J. Chem. Soc., Chem. Commun.
1985, 1588. b) D. H. R. Barton, D. Crich, Tetrahedron Lett. 1985,
26, 757. c) F. Coppa, F. Fontana, E. Lazzarini, F. Minisci, Chem.
Lett. 1992, 1299. d) D. Crich, S. M. Fortt, Synthesis, 1987, 35. e)
H. Togo, S. Matsubayashi, O. Yamazaki, M. Yokoyama, J. Org.
Chem. 2000, 65, 2816.
Me
Me
Me
Me
60
6
6
6
6
1
2
3
4
1
d
4d
3
4
a
Isolated yield.
65
6
6
6
6
6
7
8
9
5
6
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
In summary, a convenient method for tertiary carbon
radical reaction was developed. Whereas tertiary carbon
radicals are usually prepared from tertiary halides, we found
that the microwave assists the generation and subsequent
reaction of tertiary carbon radicals from tertiary xanthates.
Although the steric hindrance and the Chugaev elimination
sometimes interfere the preparation of tertiary xanthates,
tertiary alcohols are much more readily available starting
materials compared to tertiary halides. Indeed, various
xanthates were prepared and reacted with various electron
deficient alkenes in acceptable to good yields. As is the case
of our total synthesis, this microwave-assisted tertiary
carbon radical reaction will be a complementary method to
the radical initiation from tertiary halides and
photoactivation of tertiary oxalates for the intermolecular
construction of quaternary carbon centers. Application of
this microwave-assisted reaction to the total synthesis of
70
71
7
7
7
7
76
77
7
7
8
8
82
83
8
8
8
2
3
4
5
a) G. L. Lackner, K. W. Quasdorf, G. Pratsch, L. E. Overman, J.
Am. Chem. Soc. 2013, 135, 15342. b) G. L. Lackner, K. W.
Quasdorf, G. Pratsch, L. E. Overman, J. Org. Chem. 2015, 80,
6012.
1
1
1
1
1
1
1
1
1
1
2
2
7
8
C. N. Christopher, C. R. Jamison, Y. Slutskyy, D. W. C.
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8
9
0
1
4
5
6