| Non-cross-linked Polystyrene (NCPS) is one of the most widely used soluble support with easy preparation, stable stucture, and good solubility in the small polar solvent and good crystallinity in the big polar solvent. Using NCPS as soluble support, the reaction was undergone in homogeneous phase and completed in short time, and the process of the reaction could be detected online by conventional analytical methods (TLC, IR, NMR). Based on the superiority of NCPS as soluble support and the high stereoselectivity of chiral2-imidazolidinones in asymmetric reactions, in this paper using ethyl N-Boc-L-tyrosine as starting material we prepared NCPS supported2-imidazolidinone chiral auxiliary and investigated its application in asymmetric alkylation reactions.Firstly, in the literature review section, we summarized the types, synthesis and applications of2-imidazolidinones in asymmetric alkylation, Aldol condensation, Michael addition. Oxidative Coupling and Diels-alder reactions, with high stereoselectivities and chemical yields.Secondly, using ethyl N-Boc-L-tyrosine as starting material we desigened two schemes to synthesize NCPS supported2-imidazolidinone chiral auxiliary.Scheme Ⅰ:using ethyl N-Boc-L-tyrosine as starting material, NCPS supported2-imidazolidinone chiral auxiliary was prepared via a series of steps such as protection by the benzyl group, reduction, deprotection of the Boc group, reaction with phenyl isocyanate, cyclization and deprotection of the benzyl group. The overall yield is0.74%, and it is too low to the application investigation.Scheme Ⅱ:ethyl N-Boc-L-tyrosine as starting material was reacted with4-vinylbenzy chloride to introduce double bond, and then via a series of steps such as reduction, deprotection of the Boc group, reaction with phenyl isocyanate, cyclization obtained the chiral2-imidazolidinone monner containing double bond, which was copolymerized with styrene in THF with AIBN as initiator to give NCPS supported2-imidazolidinone chiral auxiliary in23.0%overall yield, and its loading capacity is1.32mmol/g. The overall yield of NCPS supported2-imidazolidinone chiral auxiliary in this method is higher than scheme I, and the chiral auxiliry prepared in this methord was used to the next application investigation.Thirdly, the application of NCPS supported2-imidazolidinone chiral auxiliary in asymmetric alkylation reactions was investigated. NCPS supported 2-imidazolidinone chiral auxiliary was acylated with propionyl chloride and phenylacetyl chloride in the presence of t-BuOK/DMAP to give NCPS supported N-propionyl2-imidazolidinone and NCPS supported N-phenylacetyl2-imidazolidinone respectively, and the yields were over90%. The asymmetric alkylation reactions of benzyl bromide with the two N-acylated NCPS supported2-imidazolidinone as chiral auxiliaries were studied using NaHMDS as base in the absence of oxygen and water and obtained the alkylated products in good yields, and then the mechnism of the alkylation reactions was proposed. The alkylated products were cleavaged by LiOH in the presence of H2O2and obtained the chiral carboxylic acid, ee>96%, which was confirmed by IR,1HNMR, and13CNMR. The recovered NCPS supported2-imidazolidinone chiral auxiliary is pure, without small molecule impurities, and the recovered yield is up to93.2%.In conclusions. NCPS supported2-imidazolidinone chiral auxiliary was prepared via a series of steps using N-Boc-L-tyrosine ethyl ester as starting material, which was applied in asymmetric alkylation reactions with high stereoselectivity and chemical yield. All the intermediate were full characterized by IR,1HNMR.13CNMR and specific rotatory power, the spectrum result was conform to the molecule structure. NCPS supported2-imidazolidinone chiral auxiliary is soluble in typical organic solvents, such as THF etc. and insoluble in EtOH, and this solubility versus recovery relationship of crystalline polymer could lead to easy purification and better recovery yield of the chiral auxiliary. |
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