but diverse pyrrolidines could be obtained, even at the
cleavage step by the introduction of an electrophilic group
Freshly prepared resin 4 was treated with an azaallyl anion,
generated in situ from N-benzylidene-N-benzylamine and
LDA, to afford the desired R-silylimine 5 bound to the resin.
The progress of the reactions was directly monitored by FT-
IR while the product was attached to the resin. The yield of
resin 5 based on the loading of resin 3 was determined by
elemental analysis.
(G) onto the nitrogen (Scheme 2). On the basis of this
Scheme 2. Protocol for Generation and Cycloaddition of
Polymer-Supported Azomethine Ylides
The prepared polymer-supported R-silylimine 5 was
reacted with N-phenylmaleimide in toluene at 180 °C for 6
h. After the reaction, the polymer was filtered off and washed
repeatedly with several organic solvents. No residue was
recovered from the filtrate, indicating that the Si-N bond
in the polymer was not easily cleaved by moisture, in contrast
to that in the product from the corresponding solution-phase
cycloaddition. The fact led us to examine the conditions of
the final cleavage step (Table 1). Although cleavage using
Table 1. Cycloaddition of Resin 5 with N-Phenylmaleimide
and Successive Cleavage Conditions
scenario, we report here on the solid-phase synthesis of
pyrrolidines from polymer-supported R-silylimines.
The polymer-supported R-silylimine 5 was prepared ac-
cording to Scheme 3. The starting resin 3 was converted to
Scheme 3. Preparation of Polymer-Supported R-Silylimine 5
time
yielda
(%)
entry cleavage reagent solvent temp (h)
R
1
2
3
4
5
H
2
O (excess)
THF
THF
rt
48
3
H
(7a ) 49b
(7a ) 90
(7a ) 90
(7b) 70
(7c) 45
HCl (excess)
TFA (excess)
rt
H
CH
2
2
Cl
Cl
2
2
rt
0.1
H
PhCOCl (3 equiv) CH
CH dCHCH
6 equiv)
Based on the loading of resin 5. b Resin 6 was recovered.
rt
12
PhCO
2
2
I
DMF
90 °C
5
2 2
CH dCHCH
(
a
an activated silyl chloride resin 4 immediately prior to use,
thus avoiding the need to store this highly reactive, moisture-
sensitive intermediate. Chlorination was accomplished by
aqueous THF was not effective under mild conditions (entry
), a stereoselective cycloaddition proceeded to give the sole
1
7
treatment of 3 with 1,3-dichloro-5,5-dimethylhydantoin.
product 7a resulting in a solid-phase synthesis without
leaving a linker trace. When acids were employed in the
cleavage reaction, the N-unsubstituted cycloadduct was
obtained in high yields (entries 2 and 3). Other electrophiles
were also tested to evaluate the utility of this simple
operation. The successful introduction of a benzoyl or an
(4) See, for example: (a) Cheng, W.-C.; Wong, M.; Olmstead, M. M.;
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Lett. 2001, 3, 3491. (f) Faita, G.; Paio, A.; Quadrelli, P.; Rancati, F.; Seneci,
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chemistry will be published elsewhere.
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Org. Lett., Vol. 4, No. 20, 2002