Diastereoselective Synthesis of Silyl-Substituted Pyrrolidines

In this paper, we report the synthesis and structural investigation of enantioenriched methylene isosteres of Hayashi-Jørgensen catalysts, and their application in organocatalysis. N-protected pyrrolidines 7b-d were prepared in high yields and excellent diastereoselectivity using a new one-pot, four-step synthetic protocol involving: (a) the formation of a silyllithium reagent (1), (b) its addition to a diaryl olefin (2) to generate a silyl-substituted diphenylethyllithium intermediate (3), (c) the highly diastereoselective addition of this intermediate to a chiral sulfinimine (4), and (d) intramolecular cyclization to the desired products. After N-deprotection, the new catalysts 8 were further evaluated in benchmark Michael additions of aliphatic aldehydes to β-nitrostyrene, under various conditions, demonstrating reactivity and stereoselectivity comparable to the Hayashi catalyst. Notably, the trimethylsilyl derivative (S)-8d showed superior enantioselectivity, transferring its stereochemical information with remarkable efficiency (up to 99% ee). Structural studies through 2D-NMR and DFT calculations revealed different conformational preferences for the corresponding enamines, providing insight into the observed catalytic performance.