Zinc mediated Barbier type propargylation of cyclic imides

Article abstract of DOI:10.1016/S0040-4039(00)01081-9

Propargylations of cyclic imides such as N-benzylsuccinimide and N-methylsuccinimide were accomplished under mild Barbier type conditions using zinc metal, propargyl bromides and catalyst. The use of PbBr₂ is essential to ensure the completion of the reaction to provided propargylated γ-hydroxylactams in high yields without the recovery of cyclic imides. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01081-9

Tetrahedron Letters 41 (2000) 6479±6482
Zinc mediated Barbier type propargylation of cyclic imides
Sung Hoon Kim* and Eun-Hyoung Han
Department of Chemistry, Konkuk University, Seoul 143-701, South Korea
Received 10 May 2000; revised 7 June 2000; accepted 23 June 2000
Abstract
Propargylations of cyclic imides such as N-benzylsuccinimide and N-methylsuccinimide were accomplished
under mild Barbier type conditions using zinc metal, propargyl bromides and catalyst. The use of PbBr2 is
essential to ensure the completion of the reaction to provided propargylated g-hydroxylactams in high
yields without the recovery of cyclic imides. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: propargylation; cyclic imide; Barbier; zinc; propargyl bromide; g-hydroxylactam.
Recently, Barbier type allylation and propargylation reactions using zinc,1 indium, tin,2 copper,3
and gallium4 are gathering attention. Most of these reactions are carried out with aldehyde,
imines1f and ketones. Additionally, it is reported that the Zn±Barbier reaction of carbonyl
compounds with propargyl halides in aqueous medium give homopropargylic alcohols in
moderate yields, with the recovery of unreacted aldehydes and a small amount of allenic
products.1c These Barbier type reactions, with relatively less reactive cyclic imides, have not been
reported in the literature to our knowledge. The only example of this type of reaction reported in
the literature is intramolecular Reformatsky reaction.5 It is well known that reactive organometallic
compounds such as alkyllithium and Grignard reagents react with cyclic imides to give alkylated
hydroxylactam products in moderate yields, together with ring opened products.6 The
unprecedented Barbier type reaction of cyclic imide itself is of great interest.
Here, we found a very ecient synthetic method for the preparation of propargylated
g-hydroxylactam compounds 3 under zinc mediated Barbier condition. The reaction of succinimide
derivatives with 2 equiv. of propargyl bromide and 3 equiv. of activated zinc,7 without any catalyst,
gave moderate yield of g-hydroxylactams with the recovery of starting material. Our attempts
.
using Lewis acid such as ZnCl2, MgBr2, TiCl4, SnCl4 and BF3 Et2O resulted in low to medium yield
of desired products. Fortunately, the use of 10 mol percent of PbBr2 promoted the reaction to
completion. The use of PbBr2 as catalyst was essential in our syntheses. At present, the role of
PbBr2 is not yet elucidated. However, we think that our work is closely related with in situ
* Corresponding author. Tel: +00 82 2 450 3420; fax: +00 82 2 3436 5382; e-mail: shkim@kkucc.konkuk.ac.kr
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01081-9

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generated allyllead reagent, which was formed by treatment of allyl bromide with aluminum and
catalytic amount of PbBr2.8 It was reported that the use of chemically activated zinc increased the
yields of Reformatsky reaction7a,b and pulsed sonoelectrochemically produced zinc powder,
greatly increased the yield of Barbier type allylation reaction.7c However, zinc granule purchased
from Aldrich without further activation gave good results in our experiments. In the case of larger
cyclic imides such as N-benzylglutarimide and N-benzyladipimide, major products were ring-open
disubstituted alcohol compound 4. Since N-benzylglutarimide adduct was found ring-open
extremely toward keto-amide,6e which is more reactive toward propargylation than glutarimide,
compounds 4 were obtained as major products. Also, it was found that propargylation of acyclic
imides such as N-benzyldiacetamide and N-benzyldicarproamide, with trimethylsilylpropargyl
bromide, a€orded exclusively 4-alkyl-1,7-bis(trimethylsilanyl)hepta-1,6-diyn-4-ol. These results
are summarized in Table 1.
Table 1
Zinc mediated Barbier type propargylation of cyclic imidesa
Typical reaction procedures are as follows; To a mixture of N-benzylsuccinimide (5 mmol),
zinc granule (10 mmol) and PbBr2 (0.5 mmol) in THF (3 mL), was added trimethylsilylpropargyl
bromide (7 mmol), slowly over 30 min. The reaction mixture was stirred at room temperature
until it became sticky greenish-gray slurry. To the reaction mixture were added another portion
of THF (7 mL) and propargyl bromide (3 mmol). The reaction was checked using 1H NMR. The
reaction mixture was quenched with saturated NH4Cl solution (30 mL), then extracted with ethyl
acetate (2Â50 mL). The ethyl acetate solution was washed with brine (10 mL), dried over sodium
sulfate, ®ltered and concentrated to give 3. Crude 3 was recrystallized from the mixture of ethyl

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acetate and hexane to give pure 3 (1.321 g, 4.38 mmol).9 Flash column chromatography of
mother liquor provided another crop of pure 3 (0.097 g, 0.32 mmol). An attempt to purify the
crude product by silica gel chromatography led to slight decomposition.
In Zn±Barbier reaction of carbonyl compounds with propargyl bromide and trimethylsilyl-
propargyl bromide in anhydrous THF, homopropargylic alcohols were obtained as major
products,1c,10 while allenic alcohols were obtained as major products with 1-bromo-2-butyne.1c
The reactions of 1-bromo-2-butyne with N-methylsuccinimide and N-benzylsuccinimide were not
1
clean, as expected. About 20% of allenic products were observed from the H NMR of crude
products.
There are many reports on the reaction of g-hydroxylactams.6,11 In order to check the versatility
of our propargylated g-hydroxylactams, 1-benzyl-5-hydroxy-5-(3-trimethylsilylprop-2-ynyl)-
pyrrolidin-2-one was reduced with NaBH3CN to give 1-benzyl-5-(3-trimethylsilylprop-2-ynyl)-
pyrrolidin-2-one in 81% yield. When triethylsilane was used as the reducing agent, fully reduced
product 6 was obtained. Prolonged exposure of this compound to weak acid a€orded 1-benzyl-
5-(2-oxopropylidene)pyrrolidin-2-one12 (Scheme 1). From the results of the above prelim-
inary experiments, the reactions of propargylated g-hydroxylactams were regarded to proceed
via N-acyliminium intermediate without the tautomerization to keto-amides.
Scheme 1. Reactions of 1-benzyl-5-hydroxy-5-(3-trimethylsilylprop-2-ynyl)pyrrolidin-2-one
Because g-hydroxylactam derivatives are precursors of acyliminium ions, which are capable of
the introduction of other alkyl groups, further synthetic application in organic synthesis are
under investigation. The allylation of cyclic imides with the same method was also carried out to
give similar results in lower yields compared to propargylation (35 to 70% isolation yields). These
allylation reactions did not show advantages over the conventional method. Therefore, we are
making a lot of e€orts to improve the yields of allylated hydroxylactams.
Acknowledgements
This work was supported ®nancially by the BSRI-1998-015-D00173 of Korea.

6482
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