Diastereoselective Alkylation of a Proline-Derived Bicyclic Lactim Ether

✍ Scribed by Daniela Hendea; Sabine Laschat; Angelika Baro; Wolfgang Frey

• Book ID: 102253762
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: German
• Weight: 217 KB
• Volume: 89
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200690181

✦ Synopsis

Dedicated to Professor Dieter Hoppe on the occasion of his 65th birthday N-Boc-protected L-proline (6) was converted into the bicyclic lactim ether (8aS)-6,7,8,8a-tetrahydro-1-methoxypyrrolo[1,2-a]pyrazin-4(3H)-one (5) in four steps (Scheme 1). Deprotonation with LDA or LHMDS and subsequent alkylation resulted in the diastereoisomeric products cis-and trans-9. The diastereoselectivity was mainly dependent on the electrophile. Whereas small alkyl halides gave preferably cis-9, sterically more-demanding alkyl halides resulted in cis/trans mixtures. Electrophiles bearing a psystem favored the trans-products 9. Some isolated cis-and trans-lactim ethers 9 were converted to the corresponding diketopiperazines cis-and trans-10 by acid hydrolysis. The structures and configurations of several compounds were confirmed by NMR and NOE experiments, as well as by X-ray crystallography (Figs. 1234).