4-Substitution on prolined irectly impactsp rotein main chain conformational preferences.T he structurale ffects of N-acyl substitution and of 4-substitution were examined by NMR spectroscopy and X-ray crystallography on minimal molecules with ap roline 4S-nitrobenzoate.T he effects of N-acyl substitution on conformation werea ttenuated in the 4S-nitrobenzoate context, duet ot he minimal role of the n!p*i nteraction in stabilizing extended conformations. By X-ray crystallography,a ne xtended conformation was observedf or most molecules. The formyl derivative adopted a d conformation that is observed at the i + 2p osition of b-turns.C omputational analysis indicated that the structures observed crystallographically represent the inher-ent conformational preferences of 4S-substituted prolines with electron-withdrawing4-position substituents. The divergent conformational preferences of 4R-a nd 4S-substituted proliness uggest their wider structure-specific application in molecular design. In particular,t he proline endo ring pucker favored by 4S-substituted prolines uniquelyp romotes the d conformation [(f, y) % (À808,0 8)] found in b-turns.I nc ontrast to other acyl capping groups, the pivaloyl group strongly promoted trans amide bond and polyproline II helix conformation, with ac lose n!p*i nteraction in the crystalline state, despite the endo ring pucker,s uggesting its special capabilities in promoting compactc onformations in f due to its strongly electron-donatingc haracter.[a] N.Supporting information (including experimentalprocedures, NMR data on 3-9,N OESY spectra for 7 and 9,X -ray crystallographic data, additional analysis of computational data, 1 Ha nd 13 CNMR spectraf or all new compounds, and coordinates for all geometry-optimized structures) and the ORCID identification number(s) for the author(s) of this article can be found under:https://doi.

We report the first rutile-promoted synthesis of sulfonylamidonitriles from aldehydes and sulfonamides with NaCN in water. This transformation has proven to work for a variety of aliphatic and aromatic aldehydes with excellent yields. The scope also extends to a variety of substituted sulfonamides. Rutile can be easily recycled and reused without significant reaction erosion. The benign nature of rutile and its natural abundance highlights this transformation as a model green reaction.