The Synthesis of Shihunineviathe Cyclopropyl Ketimine → Pyrroline Rearrangement

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Abstract
The rearrangement of cyclopropyl ketimines to pyrrolines has first been reported in 1929.1,2 More recently this reaction has been employed as one of the key steps in the syntheses of numerous alkaloids.3 In the course of our continuing interest in the conversion of cyclopropyl ketones to pyrrolidines4–6 we focused our attention on the recently identified phthalide pyrrolidine alkaloid, shihunine (Ia), which was isolated from the Chinese drug Shi-Hu.7,8 We considered it likely that shihunine could be formed in one step by heating o-carboxyphenyl cyclopropyl ketone (II) with methyl amine according to Scheme I. Inherent in such a synthesis would be the possibility of preparing various N-substituted analogs of shihunine that may be of biological interest.