Diastereoselective Alkylation of a Proline‐Derived Bicyclic Lactim Ether

N ‐Boc‐protected L ‐proline ( 6 ) was converted into the bicyclic lactim ether (8a S )‐6,7,8,8a‐tetrahydro‐1‐methoxypyrrolo[1,2‐ a ]pyrazin‐4(3 H )‐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 π ‐system 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. 1–4 ).