In tr od u ction of F u n ction a lized C1, C2, a n d C3 Un its to Im in es
th r ou gh th e Dim eth ylzin c-Air -In itia ted Ra d ica l Ad d ition
Ken-ichi Yamada, Yasutomo Yamamoto, Masaru Maekawa, and Kiyoshi Tomioka*
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, J apan
tomioka@pharm.kyoto-u.ac.jp
Received October 10, 2003
Introduction of functionalized C1, C2, and C3 units to imines was achieved by using the
dimethylzinc-air-initiated R-alkoxyalkyl radical addition as a key reaction. The addition to a Cd
N double bond chemoselectively occurred in the presence of a CdO double bond, which is one of
the advantages of this radical addition reaction over ionic addition reactions.
In tr od u ction
Resu lts a n d Discu ssion
Dir ect C1 Un it In tr od u ction . We first examined
4,4,5,5-tetramethyl-1,3-dioxolane (2) as a candidate for
an oxygen-functionalized C1 unit (Scheme 1). The reac-
tion of benzaldehyde tosylimine 1a and 2 smoothly
proceeded by the action of dimethylzinc (3 equiv) and air
to give adduct 3 in satisfactorily high 81% yield after 18
h at room temperature. However, the hydrolysis of the
tetramethylethylene acetal moiety under standard acidic
conditions failed to proceed, resulting in quantitative
recovery of 3. Consumption of 3 was observed only in
harsh refluxing 6 M HCl-dioxane conditions to give
tosylamide (4) in 53% yield without the production of the
desired product of hydrolysis of the acetal.8
We have recently reported the radical addition of
ethers to imines initiated by dimethylzinc-air.1,2 In the
presence of dimethylzinc and air oxygen,3 R-alkoxyalkyl
radicals are directly generated from ethers through
hydrogen atom abstraction, and the resulting radicals
undergo addition to imines in high yields.4-7 We have
also reported the distinctive chemoselectivity of this
reaction: the addition to CdN double bonds preferen-
tially takes place rather than that to CdO double bonds.1b
As a part of continuing studies toward the synthetic
utility of this reaction, we have examined the possibility
of using this reaction for the introduction of versatile
oxygen-functionalized carbon units to imine CdN double
bonds. The chemoselectivity as well as the mild condi-
tions of this reaction are advantageous.
tert-Butyl methyl ether (MTBE) was also examined as
a candidate for a functionalized C1 unit.4b,6i A mixture
* Corresponding author.
(6) Addition of R-alkoxyalkyl radicals to C-C multiple bonds: (a)
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(5) Addition of R-alkoxyalkyl radicals to CdO double bonds: (a)
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(8) Benzylidene-4,4,5,5-tetramethyl-1,3-dioxolane, which would be
formed by the elimination of 4, was not detected in the crude product.
10.1021/jo035496s CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/31/2004
J . Org. Chem. 2004, 69, 1531-1534
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