# Diastereoselective Synthesis of Silyl-Substituted Pyrrolidines

## TL;DR

This paper presents a new method to synthesize silyl-substituted pyrrolidines with high selectivity and efficiency, useful in organocatalysis.

## Contribution

A one-pot, four-step synthetic protocol for enantioenriched silyl-substituted pyrrolidines with high diastereoselectivity.

## Key findings

- N-protected pyrrolidines were synthesized in high yields and excellent diastereoselectivity.
- The trimethylsilyl derivative (S)-8d showed up to 99% enantiomeric excess in Michael additions.
- 2D-NMR and DFT studies revealed conformational preferences affecting catalytic performance.

## Abstract

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.