Structural Properties and Stereochemically Distinct Folding Preferences of 4,5‐cis and trans‐Methano‐ L ‐Proline Oligomers: The Shortest Crystalline PPII‐Type Helical Proline‐Derived Tetramer

The synthesis, structural properties, and folding patterns of a series of L‐proline methanologues represented by cis‐ and trans‐4,5‐methano‐L‐proline amides and their oligomers are reported as revealed by X‐ray crystallography, circular dichroism measurements, and DFT calculations. We disclose the first example of a crystalline tetrameric proline congener to exhibit a polyproline II helical conformation. Experimental evidence of PPII‐type helical arrangement (both in solution and in the solid state) of cis‐4,5‐methano‐L‐proline oligomers is supported by theoretical calculations reflecting the extent of n→π* stabilization of the trans‐amide conformation.