16 安定な面不斉を有する中員環アミン類の合成と不斉合成素子としての活用(口頭発表の部)

抄録

Nearly a half-century ago, Blomquist predicted that trans-cycloalkene should have inherent chirality. Since then, medium-sized cycloalkenes with stable planar chirality have aroused much theoretical and synthetic interest. On the other hand, their amine congener with sole planar chirality has not appeared so far, to the best of our knowledge. Here we wish to report the discovery of the remarkably stable planar chirality in a simple cyclic amine and amide 7 and their utility for asymmetric synthesis. Recently, we have reported the finding of planar chirality in nine-membered cyclic ether 1. Based on this result, we envisioned that the amine analogues should also have planar chirality and so they would be valuable chiral molecules. To realize this chemistry, we chose N-tosyl amide 7a as a target molecule, and it was successfully synthesized from neryl acetate in four steps: allylic oxidation with SeO_2, Mitsunobu reaction with methyl-N-(p-toluenesulfonyl) carbamate, base-promoted deprotection, and intramolecular Mitsunobu reaction. Analytical and semi-preparative scale HPLC using a chiral column successfully separated both enantiomers of 7a, which separation is ascertained by CD analysis of both fractions. It should be noted that the enantiomeric purity of isolated enantiopure 7a (crystal) is not significantly changed at ambient temperature for a week at least. Enantioenriched 7 thus obatained is valuable as a novel type of chiral building block. For example, hydroboration of enantio-enriched (S)-7a (>98% ee) with 9-BBN provides the stereomerically pure alcohol (3S,4R)-9 in 92% yield. The transannular reaction also proceeds in a stereospecific manner, in which a Pd(II)-catalyzed Cope rearrangement of (R)-7a (>98% ee) afforded pyrrolidine (3R,4S)-10 (>98% dr, >98% ee) in 87% yield. These results clearly show that the planar chiral cyclic amine is a valuable source for optically active heterocyclic compounds.