Fluorination-Free Synthesis of a 4,4-Difluoro-3,3-Dimethylproline Derivative

A Claisen rearrangement/iodolactamization sequence starting from commercially available trifluoroacetaldehyde methyl hemiacetal, followed by a classical chemical resolution, provided enantiomerically pure 4,4-difluoro-3,3-dimethylproline <b>(</b><i>S</i>)-<b>1</b>. No hazardous fluorination reagents were used, and the overall yield over 12 steps was greater than 28%.