Synthesis of Fmoc-protected trans-4-methylproline

Fmoc-protected trans-4-methylproline was synthesized starting from D-serine . The chiral scaffold of serine in the form of olefinated Garner's aldehyde 3 was used to control the diastereoselective formation of the new stereoce nter on the hydrogenation of allylic alcohol 4. The diastereoselectivity (s yn/anti ratio) of the process was 86:14, attained with Raney nickel. Hydrog en migration seems not to be the sole factor lowering the diastereoselectiv ity, as nickel is known not to promote double-bond migration. Instead, the moderate stereocontrol is attributed to the mobility of the side chain of 4 , which allows the attack of hydrogen on both faces of the olefin (open tra nsition state). A series of transformations led to ring precursor 8, which after recrystallization afforded the syn diastereoisomer in dr = 95:5. Prot ected trans-4-methylproline 11 was obtained from 8 in a straightforward fas hion.