Synthesis and evaluation of enantiopure silyl perfluoroalkylsulfonylimides as catalysts for asymmetric synthesis
During the course of this work we have synthesized and evaluated a series of new enantiopure silyl triflmides as catalysts for asymmetric reactions.
3-Phenyl dialkylsilyl ketones, which were the key precursors to the target silyl triflmides were prepared by 1,4-addition of the corresponding silyl cuprate to enones, and resolved by chiral HPLC. Enantiopure trans silyl ketones were successfully reduced via the corresponding tosylhydrazones by the NaBH3CN/ZnCl2 system. However, due to an isomerization of the tosylhydrazone during the reaction, cis isomers (m = 0) were reduced via the corresponding dithioketals followed by desulfurization. The diastereoselective synthesis of enantiopure silyl triflimides from enantiomerically pure compounds has been also studied.
The enantiopure trialkylsilyl triflimides were generated in situ by protodesilylation of the corresponding phenylsilanes with bis-(trifluoromethylsulfonyl)imide.
The Diels-Alder reaction of methyl acrylate with cyclopentadiene was used as the model reaction for testing the new chiral catalysts :
1) Almost all silyl triflimides were efficient catalysts giving high yields and excellent diastereoselectivities in favour of the endo-isomer.
2) the best ee's (up to 56%) were obtained from catalysts carrying an aryl group directly attached to the cyclohexane ring (m = 0) which were much better than those obtained from catalysts carrying a benzyl-type group (m = 1). Interestingly catalysts of the same configuration carrying phenyl or naphthyl group gave cycloadducts of opposite configuration.
3) When m = 0, additional substituents at position-3 or 6 of the cyclohexyl ring had little influence on the ee. However, for m = 1, a methyl group at C2 increased the ee from 3% to 35%.
4) The replacement of the methyl groups connected to the silicon atom by bulkier ethyl groups decreased the ee (m = 0).
5) When m = 0, ee's for cycloaddition reactions of N,N-dimethyl acrylamide or acryloxazolidinone with cyclopentadiene were lower than those obtained with methyl acrylate.
School:Université catholique de Louvain
Source Type:Master's Thesis
Keywords:silylating agent silyl perfluoroalkylsulfonylimi catalysis asymmetric synthesis diels alder reaction
Date of Publication:08/25/2004