Synthesis And Applications Of Camphor-based2-phenylimino-2-oxazolidine Chiral Auxiliary

The chiral oxazolidinone which was developed by Evans was synthesized by using a-amino acids chiral material. The chiral oxazolidinone auxiliary is widely used in chiral synthesis, such as chiral alkylation, aldol condensation, Diels-Alder reaction and Michael addition, and so on. This auxiliary, however, undergoes endo-cyclic cleavage rather than the required exocyclic cleavage in removal of the auxiliary with alkaline hydrolysis.The new N-acyl phenyliminooxazolidine auxiliaries results in as high diastereoselectivity in alkylation reactions, the alkylation products are easily hydrolyzed by simple alkaline hydrolysis(NaOH) without using hazardous lithium hydroperoxide to suppress the endocyclic cleavage.The abundanceand the advantageous topological bias of the skeleton of (1R)-camphor has attracted considerable interest throughout the history of organic chemistry. Camphor-based auxiliaries, such as,camphorsultam、camphor derived imidazolidinone、camphor derived oxazolidinone,and so on, were known to have excellent diastereoselectivity when the sterically congested camphor moiety was appropriately utilized.In this paper we synthesized a new camphor-based2-phenylimino-2-oxazolidine chiral auxiliary,and investigated its application in asymmetric alkylations.Firstly, we synthesized the new camphor-based2-phenylimino-2-oxazolidine chiral auxiliary. Camphor derived aminoalcoholwas synthesized from (1R)-camphor through oxidation, oximation, reduction and crystallization.Then reacted with phenyl isothiocyanate, and then treated by4-methyl benzene sulfo-chloride and sodium hydroxide to obtain the new camphor-based2-phenylimino-2-oxazolidine in87%total yield with99:1diastereoselectivity.Secondly, we using the camphor-based2-phenylimino-2-oxazolidine chiral auxiliary to induce asymmetric alkylation, discussing their asymmetric induction effect and the potential for recycling of the chiral auxiliaries.We investigated the asymmetric alkylation by using different organic bases and changing the equivalent of halides, then we found the best reaction conditions. After that the chiral auxiliarie was treated with propionyl chloride、phenylacetyl chloride and3-phenyl propionyl chloride to give the N-acylimides.We evaluated the alkylation of N-acylimides with representative alkyl halides like benzyl bromide、allylbromide、 ethyl iodide and propargyl bromide under the best alkylation condition. Except the propargyl bromide we got eight kinds of alkylation products in65%-90%yield with de>99%. Eight chiral carboxylic acids were obtained in92%-97%yield by using LiOH as cleavege reagent.Theabsoluteconfigura-tionsof carboxylic acids were deter-mined by comparing the measured optical rotations with the known values.Finaly the recyling and reuse of the chiral auxiliary was studied. The enatiomeric purities of carboxylic acids weredetermined by HPLC analysis with ee>99%. The results indicated that the stereoselectivity and yield of the recovered chiral auxiliary remained almost intact for at least three reaction cycles.The products were characterized by NMR, infrared spectroscopy, mass spectrometry, automatic polarimeter, high performance liquid chromatography, melting point apparatus and the structure consistented with the data.