C O M M U N I C A T I O N S
Table 2. Three-Component Radical Cascade
reacted unselectively with ester and oxime functions, we found that
allylzinc reagents added chemoselectively onto the oxime moiety20
to afford the desired disubstituted piperidinones 10a-c in reasonable
overall yield and high level of diastereocontrol.21 Up to three
stereogenic centers (10c) could thus be generated in a single-pot
operation. It is finally noteworthy to add that the radical cascade
can also be conducted under tin-free conditions, using oxime 3d13b,14
and DLP as an initiator. Under these conditions, 10a was obtained
in 48% overall yield (7.5:1 dr).
olefin
yielda
(%)
entry
(equiv)
oxime
R
R
′
product
1
2
3
4
5
6
7
8
9
10
2b (1)
2b (5)
2b (5)
2c (2)
2d (2)
2e (2)
2a (2)
2b (2)
2b (20)
2d (2)
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
OPiv
OPiv
OPiv
OAc
n-C6H11
OAc
CH2SiMe2Ph
OPiv
OPiv
H
H
H
H
H
Me
H
H
4b
4b
4b
4c
4d
4e
4f
4g
4g
4h
64b
88b
92b,c
81b
32d
31b
80
55
72
45
In summary, we have described a cascade reaction with high
bond-forming efficiencysup to three C-C bonds and one C-N
bondsleading to useful highly substituted piperidinones with up
to three stereogenic centers generated in one pot from readily
available reagents. The combination of radical cascades and
organometallic processes in a single pot displays a high synthetic
potential that should attract a substantial interest in the future.
H
H
n-C6H11
Acknowledgment. We gratefully acknowledge MNERT for a
grant (E.G.) and CNRS and Re´gion Aquitaine for financial support.
a Isolated yields. b dr 1:1. c Reaction run at -78 °C. d dr 3:1.
Scheme 1. Four-Component [2 + 2 + 2]-Radical Cascade
Supporting Information Available: Experimental and spectral data
for all new compounds. This material is available free of charge via
References
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P. HelV. Chim. Acta 2006, 89, 2450. (c) Russell, G. A.; Kulkarni, S. V.
J. Org. Chem. 1993, 58, 2678.
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b
a 52% based on recovered 8. 68% based on recovered 8.
(5) (a) Bazin, S.; Feray, L.; Vanthuyne, N.; Bertrand, M. P. Tetrahedron 2005,
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Scheme 2. Four-Component [2 + 2 + 2]-Radical-Organometallic
Cascade
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(16) 3c proved to be an efficient partner with various olefins providing new
substituted oximes such as 8 in good yield (50-80%) and high E/Z
selectivity (>95:5).
used to sustain the radical chain. Under these conditions, oxime
intermediate 8 was obtained16 and treated in situ with an alkyl iodide
and a Lewis acid (BF3-OEt2).17 The expected piperidinones 9a-d
were isolated in reasonable overall yield and moderate to good
diastereocontrol in favor of the trans-diastereomer (Scheme 1).18,19
Secondary radicals were found to be efficient partners, furnishing
higher degrees of stereocontrol.
(17) Miyabe, H.; Shibata, R.; Sangawa, M.; Ushiro, C.; Naito, T. Tetrahedron
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(19) For the assignment of the stereochemistry see Supporting Information.
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(21) The stereochemistry of 10b,c was assigned on the basis of X-ray structure
determination of 10a.
Organometallic reagents (Scheme 2) were also envisaged as
fourth components. Whereas alkyl-lithium and Grignard reagents
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