Enantioselective Synthesis of Spirooxindolopyrrolizidines via Catalytic 1,3-dipolar Cycloaddition of Azomethine Ylides and 3-(2-Alkenoyl)-1,3-oxazolidin-2-ones

Abstract

The ability of controlling the selectivity is an important aspect in organic synthesis. Compounds that differ in the position of a substituent are known as regioisomers. Although the regioisomers look very alike, they might possess different properties. Since Padwa and co-workers performed the first diastereoselectivity of 1,3-dipolar cycloaddition reaction in 1985, by applying a chiral non-racemic azomethine ylide, their applications has been developed as a cornerstone in organic synthesis. One of today’s challenges in this field is to control the regio-, diastereoand enantioselectivities of these reactions. Asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides offer an effective means to access chiral pyrrolidines substructures containing up to four new stereogenic centres that found in many biologically active compounds. Asymmetric multicomponent 1,3-dipolar cycloaddition of azomethine ylides with alkenes can be a great interest and useful strategies for stereoselective synthesis and develop of these class of molecules and compounds having similar structure. We reported the enantiomerically pure novel spirooxindolpyrrolizidinesby applying optically active cinnamoyloxazolidinone as chiral auxiliary and the enantioselectivities were exceptionally high. However, it requires the use of at least one equivalent of enantiopure auxiliary. To resolve this problem and in continuation of our previous work on the synthesis of spirooxindoles, 6 we applied copper complex of cyclohexane-1,2-bis(arylmethyleneamine) ligands (Fig. 1) as a catalyst to synthesis of a small library of this important class of spirooxindols. In this paper, we wish to report a highly endoand enantioselective 1,3dipolar cycloaddition reaction of azomethine ylides, derived from isatin, with electron-deficient dipolarophile by using bidendate bis(imine)-Cu(II) complex 1, that can be readily assembled from commercially available trans 1,2-cyclohexanediamine and a variety of suitable aldehyde precursors, in optimized reaction condition. Based on experiences in our previous works and literature survey, Initially, the effects of substituents of bis(imines) ligands 1(a-f) were examined using 10 mol% [Cu(OTf)2] as catalyst in a typical reaction of azomethine ylide 2a with dipolarophile 3a at room temperature in aqueous ethanol as a solvent (Scheme 1). Results are summarized in Table 1.