A novel, dichloroketene−chiral enol ether cycloaddition-based synthesis of enantiopure (+)-preussin and (−)-AHPPA has been realized. The efficient, highly stereoselective approach, which involves a Beckmann ring expansion reaction to access the key pyrrolidinone, proceeds in ca. 16% overall yield for each of the compounds.

Sequential addition of a C-nucleophile and a C-electrophile to enantiomerically pure arene tricarbonyl chromium complexes 3a,b, 6, and 8b, containing aryl bound chiral oxazoline, SAMP-hydrazone and chiral imine auxiliaries affording substituted cyclohexadienes. C-Nucleophiles included alkyl-, vinyl-, and phenyl-lithium reagents. C-Electrophiles included methyl iodide, allyl bromide, benzyl bromide, and propargyl bromides. The 1,3-cylohexadienes were obtained with a 1,5,6-substitution pattern. The results are consistent with a diastereoselective exo-nucleophilic addition to an ortho position of the complexed arene, followed by addition of the electrophile to the metal center. With allyl, ben-zyl, and propargyl groups, direct reductive elimination then yielded trans-5,6-substituted products. With methyl iodide, reductive elimination was preceded by CO insertion and acetyl cyclohexadienes were formed exclusively whose in situ deprotonation/alkylation gave products in which three C-substituents had been added across an arene double bond with complete regio-and stereocontrol. The two path-ways reflect migratory aptitude to carbonylation. An Xray structure determination of the phenyl oxazoline complex 3a allowed a rationalization of observed diastereoselectivity. Asymmetric induction was very high with the oxazoline and the SAMPhydrazone complexes (>90% de) whereas the chiral benzaldehyde imine complex 8b afforded the substituted diene aldehydes in moderate enantiomeric purity (34-58% ee). Changing the reaction medium from THF to toluene in reactions with 8b resulted in products of the opposite chirality.

Practical Asymmetric Approach to Pyrrolidinones: Efficient Synthesis of (+)-Preussin and (-)-AHPPA. -The key steps in the synthesis of the title compounds (VI) and (VII) are stereoselective cycloaddition of the ketene (III) to the enol ether (II) and efficient Beckmann ring expansion to the pyrrolidinone (V). -(KANAZAWA, A.; GILLET, S.; DELAIR, P.; GREENE, A. E.; J.

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