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.